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Objective:To investigate the effect of chemotherapy combined with sorafenib on the prognosis of FLT3 internal tandem duplication (FLT3-ITD)-positive acute myeloid leukemia and to find a more effective treatment.Methods:The clinical data of 60 patients who were newly diagnosed with acute myeloid leukemia and who received treatment in The Second Affiliated Hospital of Qiqihar Medical University from January 2015 to January 2017 were retrospectively analyzed. The patients were divided into three groups according to whether they were positive for FLT3-ITD and the treatment method they used. The observation group (FLT3-ITD-positive, n = 19) were treated with sorafenib based on routine chemotherapy. The control group 1 (FLT3-ITD-positive, n = 21) was treated only with routine chemotherapy. The control group 2 (FLT3-ITD-negative, n = 20) was treated only with routine chemotherapy. After the first and fourth courses of treatment, clinical efficacy was compared among the three groups. Results:After the first course of treatment, the complete remission rate in control group 2 was 50.0% (10/20), which was significantly higher than 15.8% (3/19) in the observation group and 4.8% (1/21) in the control group 1 ( H = 13.39, P < 0.05). After the fourth course of treatment, the complete remission rate in the observation group, control group 2, and control group 1 was 63.2% (12/19), 60.0% (12/20), and 4.8% (1/21), respectively, and the differences were statistically significant ( H = 19.21, P < 0.05). Four-year follow-up results showed that the median survival time in the observation group, control group 1, and control group 2 was 36.63, 24.15, and 45.00 months respectively. The event-free survival in the observation group, control group 1, and control group 2 was 18.00, 9.82, and 24.90 months, respectively. The median survival time and the event-free survival in the control group 2 were significantly longer than those in the observation group and control group 1 ( χ2 = 19.93, 23.04, both P < 0.001). Conclusion:Chemotherapy combined with sorafenib for treating newly-diagnosed FLT3-ITD-positive acute myeloid leukemia can provide comprehensive benefits and have advantages for survival over chemotherapy without sorafenib and chemotherapy alone.
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Objectives:To analyze the clinical features of juvenile myelomonocytic leukemia (JMML) and investigate the characteristics of diagnosis and treatment of this disease.Methods:The clinical data of seven children patients with JMML who received treatment in The First Affiliated Hospital of Xinxiang Medical University between April 2015 and February 2020 were retrospectively analyzed. The clinical efficacy of different treatments was analyzed.Results:The median age at diagnosis of JMML was 8 months and 4 days for seven children patients. Fever was the principal cause of treatment, and it was mostly accompanied by hepatosplenomegaly. The median value of peripheral blood leukocyte count was 36.1 × 10 9/L, and it was 4.5 × 10 9/L for mononuclear cell count, 88 g/L for hemoglobin level, and 47 × 10 9/L for platelet count. Myeloid immature cells were found in peripheral blood smears of six patients. Chromosome examination results revealed 7-monomer in one patient, and normal karyotype in six patients. Hemoglobin level was increased in six patients. Gene detection results revealed PTPN11+NF1 mutation in one patient, N-RAS mutation in two patients, and K-RAS mutation in one patient. Three patients gave up treatment, three patients received low-intensity chemotherapy , and these six patients died of complicated infection. One patient received allogeneic hematopoietic stem cell transplantation and the patient survived without any event after 14 months of follow-up. Conclusion:The age of JMML onset is low. JMML has poor clinical specificity. Gene detection is helpful for early diagnosis of JMML. Low-intensity chemotherapy can prolong survival period, but it can not improve prognosis. Infection is the principal cause of death in patients with JMML. Hematopoietic stem cell transplantation is the only possible method to cure the disease.
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Objective To analyze the expression and clinical significance of tumor suppressor phosphatase -tension protein gene(PTEN)in differentiated thyroid carcinoma and the relationship with the V600E gene site muta-tion of murine sarcoma viral oncogene homolog B1(BRAF).Methods The expression of PTEN was assayed by im-munohistochemical staining in differentiated thyroid carcinoma and adjacent tissues.The differences were compared between clinical pathological features.The BRAF V600E gene mutation was detected by fluorescence quantitative pol-ymerase chain reaction(PCR)and to investigate the correlation between the expression of PTEN and BRAF V600E mutation.Results The negative rate of PTEN was 78.75%(63 /80)in differentiated thyroid carcinoma,13.75%(11 /80)in adjacent tissues(χ2 =27.236,P =0.000).There were significant differences in the expression of PTEN between I -II and III -IV in TNMstage,grade I and II,and lymph node metastasis(χ2 =10.395,6.948,9.263,P =0.000,0.006,0.000).The differences were not significant in the expression of PTEN between different gender,≤45 years and >45 years different pathological types and tumor diameter <2cm and ≥2cm(χ2 =1.113,0.941, 2.301,1.567,P =0.185,0.213,0.087,0.181).There was correlation between the expression of PTEN and BRAF V600E mutations(r =0.301,P =0.004).Conclusion The expression of PTEN is involved in the occurrence and development of differentiated thyroid cancer and is associated with BRAF V600E.The PTEN has the predictive value of prognosis in tumors.
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Objective To investigate the effects of inhibiting miR-29 on growth,invasion and metastasis of pancreatic cancer PANC1 cells,and explore the potential mechanism.Methods Oligonucleotides inhibiting miR-29 (anti miR-29) and control oligonucleotides (miR NC) were used to transfect PANC1 cells to establish anti miR-29 PANC1 cells and miR NC PANC1 cells.Transient transfection of PUMA siRNA,E-cadherin siRNA or NC siRNA was used to construct cotransfected anti miR29 + PUMA-siRNA-PANC1 cells and anti-miR-29 + E-cadherin-siRNA-PANC1 cells.Number of colony formations was observed,cell survival was detected by MTT,cell apoptosis was measured by flow cytometry,cell invasion was detected by transwell chamber assay,and cell migration was detected by wound healing assay.Subcutaneous injection of anti miR-29 PANC1 cells was used to establish xenograft nude mice model,and venous injection of anti miR-29 PANC1 cells was used to establish lung metastasis nude mice model,and the subcutaneous and venous injection of PANC1 cells served as control.The growth of xenograft and the number of lung metastatic nodules were observed.TUNEL method was used to detect cell apoptosis in xenograft and immunohistochemical analysis was used to detect PUMA and E-cadherin in xenograft.Results The survival rate of PANC1,miR-NC-PANC1 and anti-miR-29-PANC1 cells was 100％,(96.8 ± 2.8) ％ and (24.4 ± 3.2) ％.The number of colony formation was (213 ± 36),(196 ± 28) and (37 ± 6) per 100 high power field.The number of transmembrane cells was (56.3 ± 9.6),(49.8-± 7.3) and (11.2 ± 3.4) per 400 high power field.The distance of cell migration was (260 ± 48),(247 ± 46) and (53 ± 7) μm.Cell apoptosis rate was (1.5 +0.9) ％,(2.6 + 0.9) ％ and (22.4 + 2.8) ％.There was statistically significant difference between anti miR 29 PANC1 cells and other PANC1 cells (P ＜0.05).The survival rate,apoptosis rate,transmembrane cells and migration distance of anti-miR-29 + PUMA-siRNA-PANC1 cells was (84.7 ± 10.9) ％,(1.3 ± 0.8) ％,(49.7 ± 6.4) per 400 high power field and (182 ± 36) μm,indicating that the effects of miR 29 inhibition on PANC1 cells were abolished (all P ＜0.05).The volume of the xenograft of PANC1 and anti-miR-29-PANC1 cells was (3 800 ±270) and (1 890 ± 160)mm3,the cell apoptosis rate was 0.93 ±0.14 and 8.26 ± 1.15,the number of metastatic lung lesions was (26.4 ± 6.5) and (8.6 ± 2.7),the PUMA positivity was (7.2 ±1.6) ％ and (43.8 ± 7.6) ％,E-cadherin positivity was (8.3 ± 3.6) ％ and (47.4 ± 5.7) ％,respectively.The xenograft volume and the number of metastatic lung nodules of anti miR29 PANC1 cells was obviously decreased or decreased,but cell apoptosis rate,PUMA positivity and E cadherin positivity were obviously increased,and the differences were all statistically significant (P ＜ 0.05).Conclusions Inhibiting miR-29 expression can decrease cell proliferation,migration and metastasis of PANC1 cells,and the potential mechanism may be associated with the upregulation of PUMA and E-cadherin.
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By now,the mutations of C-KIT gene and PDGFRA have been regarded as the most important primary incidences.The latest results have revealed the fact that the abnormal expressions of p53,p16,p21 WAF-1,p27 and E-cadherin(cDH1) which were labeled as anti-oncogenes in most of human tumors,existed in the progression of gastrointestinal stromal tumor.Therefore,we put forward the theory that gene mutaion may lead to the instability of DNA that further promotes mutation of short tandem repeat in anti-oncogene coding region,on basis of which,that finally lead to the malignant progession of gastrointestinal stromal tumor by anti-oncogene mutation.
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MicroRNA (miRNA) is a class of endogenous,single-stranded non-coding small RNA that contains 21 to 23 nucleotides and is widely distributed in eucaryon,miRNA plays an important regulatory role in cell proliferation,apoptosis,growth and development through the regulation of gene translation after transcription and expression,miRNA has a close relationship with pathogenesis and development of hepatocellular carcinoma.And in this process,part of miRNA acts as oncogenes or tumor suppressor genes.A number of miRNA,such as miR-30d,miR-221,miR-222 and miR-101,had been found to express abnormally in hepatoeellular carcinoma.Here we summarize the related progress in research of miRNA and hepatocellular carcinoma.
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Objective To investigate the expressions of Survivin and high risk-human papillomavirus (HR-HPV) in cervical carcinoma and premalignant lesion,and explore their roles in the pathogenesis of cervical carcinoma.MethodsEighty-two patients of cervical intraepithelial neoplasia(CIN)and cervical carcinoma were enrolled,including 25 CIN Ⅰ,23 CIN Ⅱ -Ⅲ and 34 cervical carcinoma.Twenty normal cervicals were chosen as control.The expression of Survivin was examined by immunohistochemical assay(SP),and the infection of HR-HPV was measured by polymerase chain reaction (PCR).ResultsExpressions of Survivin and HR-HPV of patients with cervical carcinoma [ 85.3％(29/34)and 88.2％ (30/34) ]were higher than those in CIN [ 52.1％ (25/48) and 54.2％ (26/48) ](P ＜ 0.05 ),CIN were higher than those in normal cervicals [ 0 and 10.0％ ( 2/20 ) ](P ＜ 0.05 ),CIN Ⅱ - Ⅲ [ 65.2％ ( 15/23 ) and 73.9％ ( 17/23 ) ]were higher than those in CIN Ⅰ [ 32.0％ ( 8/25 ) and 28.0％ (7/25) ](P ＜ 0.05 ).Survivin positive expression in cervical carcinoma was correlation with histological grade,but was no correlation with (P ＜ 0.05),age,clinical stage and pathology typing (P ＞ 0.05 ).HR-HPV infection was no correlation with age,clinical stage,histological grade and pathology typing (P ＞ 0.05).Positive correlation between the Survivin positive expression and HR-HPV infection was observed in cervical carcinoma(r =0.403,P ＜0.05).ConclusionIt suggests that Survivin may play an important role in the occurrence and development of cervical carcinoma together with HR-HPV.
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Objective To investigate the influences of cytarabine on Survivin gene expression in human leukemia K562 cell line and discuss the mechanism of drug resistance in chemotherapy. Methods The IC50 of cytarabine was chosen by MTr assay. The K562 cells were exposed to certain concentration of cytarabine for about 24 hours and 48 hours. The expression levels of Survivin gene were detected by RT-PCR and Western-blot. Results After exposed to cytarabine for 24 hours and 48 hours, the Survivin mRNA level of K562 cells was significantly elevated about 1.92 and 3.38-fold, and the protein expression level was elevated about 1.92 and 2.64-fold. Conclusion An elevated expression of Survivin was tested in K562 cells treated by cytarabine. Consequently, the elevated expression of Survivin could resist apoptosis induced by chemotherapeutic agent which probably associated with chemotherapeutic drug resistance.
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BACKGROUND: Apoptosis plays a crucial role in carcinogenesis, as well as in development and tissue homeostasis. Terminal deoxyribonucleotidyl transferase mediated neck end labelling (TUNEL) and in situ nick end labelling (ISEL) have been used to investigate the apoptosis in tissues. Since the introduction of the M30 monoclonal antibody to overcome drawbacks of TUNEL and ISEL, the apoptosis in various tumors, with the exception of pulmonary carcinomas, has been studied. In this study, attempts were made to examine the correlation of apoptosis in non-small cell carcinomas, using both M30 and the expression of p53 protein, with the clinicopathological factors. MATERIAL AND METHOD: Forty five patients with surgically resected non-small cell carcinomas were included. Immunohistochemical staining with M30 and p53 monoclonal antibody were performed, and their expressions compared with the clinicopathological features. The overall survival time and recurrence-free survival time were calculated, and the factors influencing the survival time analyzed using a univariate analysis. The effects of the expression stati of M30 and p53 on the risks of cancer related to both death and recurrence were evaluated using a multivariate analysis. RESULT: The p53 positive group had many more M30 positive cells than the p53 negative group (p53 positive group; 61.7+/-26.8 cells vs. p53 negative group; 45.6+/-29.6 cells, p=0.005) and significantly more p53 positive patients showing at least 10 positive cells (apoptotic index, AI > or =1) on M30 staining (p53 positive group; 52.4% [11/21] vs. p53 negative group 16.7% [4/24], p=0.025). In the univariate analysis, the survival times in relation to smoking (pack-year), performance status (PS) and AI showed significant differences. The multivariate analysis demonstrated the relative risk (R.R) of cancer death increased almost 7.5-fold (R.R 7.482; 95% CI 1.886~29.678; p=0.004) and the risk of recurrence almost 3.8-fold (R.R 3.795; 95% CI; 1.184~12.158; p=0.025) in the high AI (> or =1) compared to the low AI (<1) group. There was no prognostic effect of p53 expression on the survival time or risk of cancer death and recurrence. CONCLUSION: In non-small cell lung carcinomas, M30 immunohistochemistry was an excellent method for analyzing apoptosis; the high apoptotic index could be an adverse prognostic predictive factor.
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Humans , Apoptosis , Carcinogenesis , Cell Death , DNA Nucleotidylexotransferase , Homeostasis , Immunohistochemistry , In Situ Nick-End Labeling , Lung Neoplasms , Lung , Multivariate Analysis , Neck , Recurrence , Smoke , SmokingABSTRACT
Objective To study the expression of p73 gene in lung cancer and tumorigenesis, progression of lung cancer in the elderly. Methods The expression of p73 protein in 65 cases of lung cancer, adjacent tissues of cancer and normal tissues was determined by immunohistochemical SABC method. The results were analysed by combining the clinicopathological data and the prognosis. Results The results showed (1)the expression level of p73 protein in the cancer group was significantly different from the rest groups(47 7%,9 2%,4 6%, P 0 05),but it was correlated with the clinical stage (60 5%,22 7%) and survival time of the patients (72 2%,16 0%, P
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Objective:To investigate the suppression effect and apoptosis of the colon cell line HT-29 treated with adenovirus-expressed human hyperplasia suppressor gene(hHSG)and hyperthermia.Methods:Replication-defective recombinant adenovirus containing hHSG was constructed,and then infected into HT-29 cell line to detect its overexpression by western blot.The synergic effect with hyperthermia was observed,cell survival was assessed using Vi-CELL TMXR Cell Viability Analyzer,and cell apoptosis and cell cycle distribution were determined by flow cytometry.Results:After the cells were treated with 100 MOI(multiplicity of infection)Ad5-hHSG and heated at 42 ℃ for 1 h,the number of viable cells decreased sharply,compared with single treatment with Ad5-hHSG or 42 ℃ for 1 h(P
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Objective: To study the effect of hyperplasia suppressor gene (HSG) in inducing vascular smooth muscle cell apoptosis and the underlying mechanisms. Methods: The cultured VSMCs were transfected with an adenoviral vector containing rat HSG gene. Effects of HSG on VSMC apoptosis were investigated by fluorescent dye staining to detect the tact of nuclei, and by flow cytometry to define the content of DNA and to detect the levels of caspase-3. The expressions of Bcl-2 and Bax were also performed by Western blot analysis. Results: The increased expression of HSG in VSMCs infected with AdHSG induced apoptotic cell death detected by flow cytometry assay and nucleic staining. Compared with control groups, HSG induced vascular smooth muscle cell apoptosis 72 h after infected with adenoviral vector (39.6%?3.2% vs. 2.6%?0.9%,P
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Objective To evaluate the effects of adenovirus mediated gene transfer of TIMP 2 and PTEN on invasion of human U87 glioma cells in vitro . Methods U87 cells were transinfected with AdTIMP 2 and AdPTEN in vitro . The mRNA and protein expressions of TIMP 2 and PTEN were detected with RT PCR and Western blotting, respectively. The relative activity of MMP 2 and MMP 9 was determined by gelatin zymogram, and invasion of U87 in vitro was observed using Boyden chamber. Results Gene and protein expressions of PTEN and TIMP 2 were shown to be up regulated when U87 was transinfected with AdPTEN and AdTIMP 2. The number of invasion cells of U87 infected with AdX gal, AdPTEN, AdTIMP 2 and PTEN+TIMP 2 was 55 64 13 27, 48 26 14 75, 35 27 10 94, 27 38 12 81, and 19 16 5 45, respectively. In vitro invasion of glioma cells was significantly inhibited after infected with AdTIMP 2 and/or AdPTEN, while the inhibition effect was more remarkable in the combined group than that in single group, and it was not consistent with the change in MMPs activity. Conclusion These results imply that combined TIMP 2 and PTEN gene therapy mediated by adenorirus may be useful for anti invasion therapy of malignant glioma
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Objective To study the significance of expressions of smad_4mRNA,TGF-?_1, and TGF-?R_1 in pancreatic carcinoma(PC) . Methods Smad_4mRNA was detected by in situ hybridization. TGF-?_1 and TGF-?R_1 were detected by immunohistochemical method. Results The positive rates of smad_4mRNA,TGF-?_1 and TGF-?R_1 were singnificantly lower in 53 slices of pancreatic carcinoma than those in 25 slices of paracancerous tissue (all P
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Objective To detect the level of serum melanoma-inbibiting activity (MIA) in patients with uveal melanomas, and investigate the value of MIA in diagnosing and inspecting uveal melanomas. Methods Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of MIA in peripheral serum of 27 patients with uveal melanoma, 6 with melanocyte tumor, 7 with other ocular tumors and 16 healthy individuals, respectively. Results The concentration of MIA in patients with uveal melanoma was significantly higher than that in the healthy ones (16 individuals) and the patients with adenoma of non pigmented ciliary epithelium (4 patients), retinoblastoma (2 patients), and retinal angioma 91 patient). The concnetration of MIA in patients with uveal melanoma without scleral infiltration or remote metastasis was obviously lower than that in the patients with scleral infiltration or remote metastasis, but didn′t differ much from which in the patients with melanocyte tumor. In the patients with uveal melanoma without infiltration or remote metastasis, there was no significant difference of MIA level between patients with spindle cell and mixed and epithelioid cell. Conclusion The level of serum MIA may be an effective index in diagnosing uveal melanoma, which can monitor the metastasis of uveal melanoma.
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AIM: To observe the effect of simvastatin on the proliferation of vascular smooth muscle cells(VSMCs) induced by serum and growth factor PDGF-BB and the effect of simvastatin on the expression of PTEN,a important regulator of G 1/S cell cycle transition. METHODS: The DNA synthesis was determined by -TdR incorporation, cell cycle was examined with flow cytometry, the protein level of PTEN was measured by Western blot method. RESULTS: (1)Simvastatin inhibited -TdR incorporation in a dose dependent manner. (2) Flow cytometric DNA analysis revealed that simvastatin induced significantly enhancement of G 0/G 1 phase and decrease in S phase VSMCs.(3)Simvastatin increased protein level of PTEN and mevalonate, a metabolite of HMG-COA, reversed the effect of simvastatin on PTEN protein expression. CONCLUSION: Simvastatin may inhibit proliferation of VSMCs and retarded cell cycle in G 0/G 1 phase by increasing PTEN expression through inhibiting synthesis of mevalonate.
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A Review] The oncogene expression and growth of leukemic cells could be inhibited by antisense oligonucleotide. The selection of target genes is the key step in the research of antisense oligonucleotide on leukemia. The article would review the status and prospect of some target genes of leukemia in the investigation of antisense oligonucleotide.
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Purpose To investigate nucleoside diphosphate kinase (NDPK ) expression of tumor metastasis suppressor gene nm23 in heterotransplanted model of retinoblastoma(RB) in nude mice,and analyse the correlation between the expression of nm23 gene and the formation and progression of heterotransplanted RB. Methods SP immunohistochemical method was used to detect the expression of nm23 gene product NDPK in 20 tumors of heterotransplanted RB model and normal retinal tissue. Results The negative staining of nm23/ NDPK was found in normal retinal tissue , whereas 100% expression rate in RB tumors with positive number of 48.73?2.37. No statistical significance of the expression of nm23/ NDPK was observed between the intraocular growth phase (I～Ⅲ grade) and invasive phase (Ⅳ～Ⅴ grade) in heterotransplantedRB tumors. Conclusion The function of nm23 gene as a tumor metastasis suppressor in heterotransplanted RB tumors was less prominent ,but it may play a role in carcinogenesis and progrssion of RB and may predict poor prognosis.
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Objective To determine the biological effect of p27 KIP1 on gastric carcinoma cells SGC7901. Methods The total length of p27 KIP1 cDNA was transfected into human gastric cancer cells SGC7901 by lipofectin transfection. Expression of p27 KIP1 in protein or mRNA level was examined by Western blotting and RNA dot blotting respectively. Effect of p27 KIP1 on cell growth was observed by trpan blue exclusion assay. Tumorigenicity test in nude mice was applied to assess the biological effect of p27 KIP1 in vitro. Results Expression of p27 KIP1 in protein or mRNA increased evidently in SGC7901 cells transfected with p27 KIP1 . The cell growth was reduced by 42% about 48h after the induction with Zn 2+ ,which was determined by cell viability assay. The tumorigenicity of nude mice was reduced evidently(P
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ObjectiveTo study the effect of anti-oncogene p15 and p16 on the proliferation of human cholangiocarcinoma cell line.MethodsThe cDNA of anti-oncogene p15 and p16 was constructed into pcDNA3-neo plasmid carrier. The human cholangiocarcinoma cell line QBC939 were transfected with the recombinants pcDNA3p15 and pcDNA3p16 using lipofectin, respectively. The expression products were analyzed by Western blot. Cell viability and death were measured with MTT assay. Cell cycle was determined by flow cytophotometry and the formation of cell clone was detected. Results The growth of QBC939 cells was inhibited. The flow cytophotometry verified p15 and p16 induced QBC939 cell G1 blockade. Conclusion Anti-oncogene p15 and p16 together lead to the inhibition of cell cycle.