RESUMEN

Primitive neuroectodermal tumor (PNET) is a rare and highly malignant neoplasm composed of small round cells, which frequently occurs in children and adolescents. PNET originating from the prostate is even rarer. We report a case of PNET of the prostate with notalgia and paraplegia as the initial symptoms. Positron emission tomography-computed tomography scanning showed hypodense and hypermetabolism on the prostate; subsequently, we ascertained the diagnosis by transrectal ultrasound-guided biopsy. The patient underwent local vertebral radiotherapy combined with five courses of systematic chemotherapy. Disease progressed after 11 months, and the overall survival was 17 months.

Asunto(s)

RESUMEN

Solid-state near-infrared (NIR) light-emitting devices have recently received considerable attention as NIR light sources that can penetrate deep into human tissue and are suitable for bioimaging and labeling. In addition, solid-state NIR light-emitting electrochemical cells (LECs) have shown several promising advantages over NIR organic light-emitting devices (OLEDs). However, among the reported NIR LECs based on ionic transition-metal complexes (iTMCs), there is currently no iridium-based LEC that displays NIR electroluminescence (EL) peaks near to or above 800 nm. In this report we demonstrate a simple method for adjusting the energy gap between the highest-occupied molecular orbital (HOMO) and the lowest-unoccupied molecular orbital (LUMO) of iridium-based iTMCs to generate NIR emission. We describe a series of novel ionic iridium complexes with very small energy gaps, namely NIR1-NIR6, in which 2,3-diphenylbenzo[g]quinoxaline moieties mainly take charge of the HOMO energy levels and 2,2'-biquinoline, 2-(quinolin-2-yl)quinazoline, and 2,2'-bibenzo[d]thiazole moieties mainly control the LUMO energy levels. All the complexes exhibited NIR phosphorescence, with emission maxima up to 850 nm, and have been applied as components in LECs, showing a maximum external quantum efficiency (EQE) of 0.05 % in the EL devices. By using a host-guest emissive system, with the iridium complex RED as the host and the complex NIR3 or NIR6 as guest, the highest EQE of the LECs can be further enhanced to above 0.1 %.

RESUMEN

OBJECTIVE: To observe the effect of Shugan Liangxue Decoction (, SGLXD) on estrogen receptor α (ERα) in human breast cancer cells. METHODS: The effect of SGLXD (0.85-5.10 mg/mL) on the proliferation of breast cancer cells were evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The nuclear ERα protein levels in MCF-7, T47D and ZR-75-1 cells which treated by SGLXD for 24 h were examined by western blot and immunofluorescence assay. MCF-7 and MDA-MB-231 cells were treated by 17ß-estradiol (E2) with or without SGLXD, for 24 h, and the E2 targeted genes c-myc and bcl-2 protein product was evaluated by western blot. RESULTS: SGLXD showed dose-dependent inhibition on the proliferation of MCF-7, T47D and ZR-75-1 cells, but did not inhibit the proliferation of MDA-MB-231 cells. Furthermore, the promotive effect on cell growth induced by E2 was also significantly inhibited by SGLXD treatment. With the treatment of 1.70, 3.40, 5.10 mg/mL SGLXD, the nuclear ERα protein level was reduced to 88.1%, 70.4% and 60.9% in MCF-7 cells, and was decreased to 43.0%, 38.4% and 5.9% in ZR-75-1 cells as compared with the control group. In T47D cells, the nuclear ERα protein was down-regulated to 51.3% and 4.3% by 3.40 and 5.10 mg/mL SGLXD treatment. The down-regulative effect of SGLXD on nuclear ERα was confirmed by immunofluorescence assay. SGLXD decreased the protein product of c-myc and bcl-2. CONCLUSIONS: SGLXD may exhibit selective inhibition effect on the proliferation of ER positive breast cancer cells. SGLXD reduced the nuclear ERα expression and the protein product of E2 target gene c-myc and bcl-2.

Asunto(s)

RESUMEN

AIM: To investigate associations between the IL-17 rs2275913 G>A and rs763780 T>C polymorphisms and susceptibility to gastric cancer in Asian populations. METHODS: We reviewed studies published up to 2014 on IL-17 polymorphisms with gastric cancer susceptibility systematically. Relevant articles were identified in the MEDLINE, Science Citation Index, Cochrane Library, PubMed, EMBASE, CINAHL and Current Contents Index databases. We used version 12.0 STATA statistical software to evaluate the statistical data. Two reviewers abstracted the data independently. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated. RESULTS: Seven independent, case-control studies were chosen for the meta-analysis, which included 3210 gastric cancer patients and 3889 healthy controls. The overall estimation showed a positive association between the IL-17 rs2275913 G>A polymorphism and the occurrence of gastric cancer for five genetic models (all P < 0.05) and similar results were observed for the IL-17 rs763780 T>C variation with four genetic models (all P < 0.05), but not for the dominant model (P > 0.05). Subgroup analysis by country revealed that the rs2275913 G>A and rs763780 T>C polymorphisms may be the main risk factor for gastric cancer in Chinese and Japanese populations. CONCLUSION: The IL-17 gene may be significantly correlated with gastric cancer risk in Asian populations, especially those carrying the rs2275913 G>A and rs763780 T>C polymorphisms.

Asunto(s)

RESUMEN

OBJECTIVE: This study aims to explore the correlations of genetic polymorphisms in LIG4 and HSPB1 genes with the radiation-induced lung injury (RILI), especially radiation pneumonitis (RP), in lung cancer patients. METHODS: A total of 160 lung cancer patients, who were diagnosed with inoperable lung cancer and received radiotherapy, were included in the present study from September 2009 to December 2011. TaqMan Real-Time PCR (RT-PCR) was used to verify the SNPs of LIG4 and HSPB1 genes. Chi-square criterion was used to compare the differences in demographic characteristics, exposure to risk factors, and SNPs genotypes. Crude odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated by logistic regression analysis. All statistical analyses were conducted in SPSS 18.0. RESULTS: A total of 32 (20.0%) lung cancer patients had RP after receiving radiotherapy. Of the 32 cases, 4 cases were of grade 2, 24 cases were of grade 3, and 4 cases were of grade 4. However, our results indicated that the general condition and treatment of all patients had no significant difference with RP risk (P > 0.05). Meanwhile, our results revealed that there was no significant association between the frequencies of LIG4 rs1805388 and HSPB1 rs2868371 genotype distribution and the risk of RP (P > 0.05). CONCLUSION: In conclusion, we demonstrated that the genetic polymorphisms in LIG4 rs1805388 and HSPB1 rs2868371 were not obviously correlated with the risk of RP and RILI of lung cancer.

Asunto(s)

RESUMEN

OBJECTIVE: To investigate the relationship between the PARP-1 rs3219073 C>G polymorphism and susceptibility to lung cancer in Chinese people. METHODS: In accordance with the case-control study principle, 645 of the patients had histologically recognized primary lung cancer, among them 240 had squamous carcinoma, 217 had adenocarcinoma, and 188 had small-cell lung cancer. The control group consisted of 643 healthy subjects who had received a physical examination. Extracts of peripheral blood were taken from all subjects, and genomic DNA was extracted by the phenol-chloroform method. RESULTS: After adjusting for age and smoking status, the results show significant association between genetic variations in the rs3219073 C/C genotype and an increased risk of lung cancer (p=0.045, odds ratio [OR]=0.625). After combining C/G, G/G is still statistically significant (p=0.042, OR=0.637). Hierarchical analysis found that the number of subjects with a G/G genotype in the adenocarcinoma group is lower than in the control group (p=0.015, OR=0.543). After combining C/G, G/G is still statistically significant (p=0.027, OR=0.595). After correcting for age and smoking status, the group with C/G genotype and the group with G/G genotype both appear to have a reduced risk for lung cancer compared with the control group (p=0.045, OR=0.566; p=0.013, OR=0.489). The combination of C/G and G/G displays a more statistically significant difference (p=0.018, OR=0.528). CONCLUSIONS: The study found that PARP-1 rs3219073 C>G polymorphism is indeed associated with lung cancer susceptibility. The carriers of G alleles may have reduced risk of lung cancer, especially adenocarcinoma.

Asunto(s)

RESUMEN

Many existing studies have demonstrated that p16 promoter methylation might be correlated with the clinicopathologic features of colorectal cancer (CRC), but individually published results are inconclusive. This meta-analysis aimed to derive a more precise estimation of the relationships between p16 promoter methylation and the clinicopathologic features of CRC. We searched the CISCOM, CINAHL, Web of Science, PubMed, Google Scholar, EBSCO, Cochrane Library, and CBM databases from inception through August 1, 2013. Meta-analysis was performed using the STATA 12.0 software. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated under fixed- or random-effects models. Twenty-seven clinical cohort studies were included with a total of 3311 CRC patients. Our meta-analysis results revealed that p16 promoter methylation was associated with pathological characteristics of CRC (tumor, nodes, metastasis stage: OR=1.55, 95% CI: 1.14-2.13, p=0.006; lymph node metastasis: OR=2.40, 95% CI: 1.37-4.19, p=0.002; histologic grade: OR=2.72, 95% CI: 1.63-4.54, p<0.001; Dukes stage: OR=2.06, 95% CI: 1.57-2.71, p=0.002; tumor size: OR=1.99, 95% CI: 1.03-3.85, p=0.041; location: OR=2.49, 95% CI: 1.95-3.18, p<0.001, respectively). Subgroup analysis by ethnicity suggested that there were also significant correlations between p16 gene promoter methylation and pathological characteristics of CRC among both Caucasian and Asian populations (all p<0.05). Our meta-analysis suggests that promoter methylation of the p16 gene may be strongly correlated with the clinicopathologic features of CRC. Thus, p16 gene promoter methylation may be a potential biomarker for CRC.

Asunto(s)

RESUMEN

Our study aims to discuss the association between inflammation-related factors such as single nucleotide polymorphisms (SNPs) with susceptibility and recurrence in nasopharyngeal carcinoma. We used Taqman real-time polymerase chain reaction (PCR) to characterize the genetic variation of five SNPs in 194 nasopharyngeal carcinoma patients and 231 healthy subjects. All statistical analysis is performed with statistical product and service solutions v13.0; odds ratio (OR) value and 95 % confidence interval (CI) were calculated. There is no relationship between TGFß1 -869 T/C, IL-6 -634C/G, TGFß1 -509C/T, IL1 -511C/T and nasopharyngeal carcinoma susceptibility. Both single factor and multiple factors analysis showed that IL1a -889 T/T genotype is significantly associated with nasopharyngeal carcinoma in decreasing the risk of nasopharyngeal carcinoma. A highly significant association was found between IL1a -889 T/T genotype and protective genotype as defined by various pathological types. This is more obvious in the protective genotype of the non-keratin-type squamous carcinoma undifferentiated type. We also discovered that genotype G/G and C/G + G/G of IL6 -634 gene are associated with reduced recurrence of nasopharyngeal carcinoma. IL1a -889 gene polymorphism and susceptibility is related to nasopharyngeal carcinoma and can potentially decrease the risk of nasopharyngeal carcinoma in the Han Chinese population in north China. IL1-889 TT genotype is protective genotype for nasopharyngeal carcinoma. We have provided evidence that the GG genotype of the IL6 -634 gene is associated with recurrent risk of nasopharyngeal carcinoma. The G allele is the protective gene of nasopharyngeal carcinoma recurrence.

Asunto(s)

RESUMEN

This meta-analysis of published cohort studies was conducted to evaluate whether promoter methylation of the secreted frizzled-related protein 1 (SFRP1) gene contributes to colorectal carcinogenesis. The Web of Science (1945 ~ 2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966 ~ 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), and the Chinese Biomedical Database (CBM) (1982 ~ 2013) were searched without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. We calculated odds ratio (OR) and its 95 % confidence interval (95 % CI) to estimate the correlations between SFRP1 promoter methylation and colorectal carcinogenesis. In the present meta-analysis, 8 cohort studies with a total of 942 patients with colorectal cancer (CRC) were included. The pooled results revealed that the frequency of SFRP1 promoter methylation in cancer tissues were significantly higher than those of normal, adjacent, and benign tissues (cancer tissues vs. normal tissues: OR = 31.49, 95 % CI = 17.57 ~ 56.44, P < 0.001; cancer tissues vs. adjacent tissues: OR = 5.95, 95 % CI 3.12 ~ 10.00, P < 0.001; cancer tissues vs. benign tissues: OR = 3.01, 95 % CI 1.72 ~ 5.27, P < 0.001; respectively). Furthermore, ethnicity-stratified analysis indicated that SFRP1 promoter methylation was strongly correlated with colorectal carcinogenesis among both Asians and Caucasians (all P < 0.05). Our findings provide empirical evidence that SFRP1 promoter methylation may be correlated with the pathogenesis of CRC.

Asunto(s)

RESUMEN

To investigate the association of LIG1 with the risk of lung cancer, all subjects of unrelated ethnic Han Chinese in Liaoning Province were involved in a hospital-based case-control study. The case group consisted of 370 histologically diagnosed lung cancer patients; 314 controls were selected from cancer-free patients during Dec. 2009 to Dec. 2011. LIG1 rs1050298SNP were analyzed by TaqMan real-time PCR method. All statistical analyses were performed with Statistical Product and Service Solution sv13.0 (SPSS). The genotype distribution frequency of LIG1 rs1050298 SNP displayed significant difference between the case and the control group. Individuals carrying the LIG1 rs1050298 T genotype had higher risks of lung cancer, especially those with squamous cell carcinoma.

Asunto(s)

RESUMEN

The current meta-analysis of case-control studies was conducted to evaluated the relationships of genetic polymorphisms in the CYP1A1 and CYP1B1 genes with the susceptibility to bladder cancer, aiming at determine whether these polymorphisms may contribute to the pathogenesis of bladder cancer. Related articles were determined via searching the following electronic databases without any language restrictions: PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases for relevant articles published before November 1st, 2013. STATA 12.0 software was also selected to deal with statistical data. The relationships were evaluated using the pooled odds ratios (ORs) and their 95% confidence intervals (CI). Eleven case-control studies with a total of 2,609 bladder cancer patients and 2,634 healthy subjects met the inclusion criteria. The results of our meta-analysis demonstrated that CYP1A1 genetic polymorphisms were associated with increased risks of bladder cancer (allele model: RR = 1.18, 95% CI 1.07-1.30, P = 0.001; dominant model: RR = 1.15, 95% CI 1.05-1.27, P = 0.003; respectively), especially among 11599G>C, 2455A>G, 3810T>C, and 113T>C polymorphisms. A subgroup analysis by ethnicity was conducted to investigate its effect on susceptibility to bladder cancer. The subgroup analysis results revealed positive significant correlations between CYP1A1 genetic polymorphisms and bladder cancer risk among Asians (allele model: RR = 1.26, 95% CI 1.10-1.44, P = 0.001; dominant model: RR = 1.22, 95% CI 1.08-1.38, P = 0.001), but not among Caucasians (all P < 0.05). Nevertheless, we observed no significant correlations between CYP1B1 genetic polymorphisms and bladder cancer risk (all P > 0.05). Our meta-analysis indicates that CYP1A1 genetic polymorphisms may be involved in the pathogenesis of bladder cancer, especially among 11599G>C, 2455A>G, 3810T>C, and 113T>C polymorphisms. However, CYP1B1 genetic polymorphisms may not be important determinants of bladder cancer susceptibility.

RESUMEN

OBJECTIVE: To investigate the prognostic influence on long-term overall survival (OS) from treatment with Chinese medicine (CM) and chemotherapy or targeted therapy in advanced non-small-cell lung cancer (NSCLC) patients. METHODS: The clinical data of 206 advanced NSCLC patients who were treated with CM and Western medicine in Beijing Cancer Hospital from April 1999 to July 2013 were retrospectively analyzed. Long-term survivors were defined as OS ≥ 3 years after treatment with CM and chemotherapy. Twenty-eight patients had OS ≥ 3 years, 178 had OS < 3 years, and all clinical data were statistically analyzed with the Cox model. Variables were gender, age, smoking status, performance status (PS) score, pathological type, clinical stage, first-line chemotherapy, targeted therapy, and use of CM. Univariate survival analysis was performed using the Kaplan-Meier method and log-rank sequential inspection. Multivariate survival analysis was used to analyze the meaningful factors of univariate survival analysis with the Cox model. RESULTS: The survival rate of patients with OS ≥ 3 years was 13.6% (28/206). Cox multivariate regression analysis showed that PS score, clinical stage, disease control rate to first-line chemotherapy, and use of CM were independent factors of longterm OS (all <0.05). However, gender, age, smoking, and use of epidermal growth factor receptor tyrosine-kinase inhibitor were not significant (P>0.05). CONCLUSION: PS score, clinical stage, disease control rate to first-line chemotherapy, and use of CM are probably independent prognostic factors for long-term OS in patients with advanced NSCLC.

Asunto(s)

RESUMEN

Many existing studies have demonstrated that the macrophage inhibitory cytokine-1 (MIC-1) might be a powerful diagnostic biomarker in patients with pancreatic cancer; but individually published results are inconclusive. This meta-analysis aimed to derive a more precise estimation of the diagnostic performance of serum MIC-1 in pancreatic cancer. We searched CISCOM, CINAHL, Web of Science, PubMed, Google Scholar, EBSCO, Cochrane Library, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases from their inception through August 1st, 2013. Meta-analysis was performed using Meta-Disc version 1.4 and STATA version 12.0 software. Crude standardized mean difference (SMD) and their 95% confidence intervals (CI) were estimated. Data from selected studies were pooled to yield summary sensitivity, specificity, positive and negative likelihood ratio (LR), diagnostic odds ratio (DOR), and receiver operating characteristic (SROC) curve. Ten case-control studies were included in this meta-analysis with a total of 1235 pancreatic cancer patients and 730 healthy subjects. Our meta-analysis results revealed that serum MIC-1 levels in pancreatic patients were higher than those of healthy subjects (SMD=1.38, 95% CI=1.15-1.62, p<0.001). The area under the SROC curve was 0.92 (SE=0.020); the pooled sensitivity was 0.79 (95% CI=0.77-0.82); and the pooled specificity was 0.86 (95% CI=0.84-0.88). The pooled positive LR was 6.20 (95% CI=1.24-30.91); the pooled DOR was 35.73 (95% CI=18.52-68.93). In conclusion, the present meta-analysis suggests that serum MIC-1 may be a useful diagnostic biomarker with high sensitivity and specificity for identifying pancreatic cancer.

Asunto(s)

RESUMEN

Radiation-induced lung toxicity (RILT), leading to radiation pneumonia or fibrosis, is a primary problem of radiation therapy. The pathogenesis of RILT remains unclear. In this study, we used a rat model of RILT to examine the expression of aquaporins (AQPs) after radiation injury. Sprague Dawley rats were given a single dose of 17 Gy (dose rate of 3.0 Gy/min) of X-irradiation to the thorax. Rats that survived acute pneumonitis (at 1-4 weeks) were evaluated weekly for the expression of AQP1 and AQP5 in the lung by immunohistochemical and reverse transcription polymerase chain reaction (RT-PCR) analyses. Immunohistochemical analysis showed that AQP1 protein was expressed in the capillary endothelium, and its level was significantly decreased after irradiation. AQP5 protein was expressed in the alveolar epithelium, and its level was increased between Days 7 and 14 after irradiation but decreased at Day 28, compared with the sham group. The RT-PCR results were consistent with the immunohistochemical analysis results. In summary, this study provides the first report of AQP1 and AQP5 expression in a model of radiation-induced pulmonary inflammation and edema. Decreased levels of AQP1 and AQP5 after irradiation suggest that these proteins play a role in the pathogenesis of RILT.

Asunto(s)

Asunto(s)

RESUMEN

OBJECTIVE: To explore the anti-fatigue effect of Renshen Yangrong Decoction (RYD): in mice. METHODS: One hundred Kunming mice were randomly divided into 5 groups with 20 mice in each: group. The negative control group was treated with distilled water, the positive control group was treated with Shiyiwei Shenqi Tablet (, 1.0 g/kg), the high-, medium- and low-dose RYD groups were treated with 42.0, 21.0 and 10.5 g/kg of RYD daily, respectively, by gastric infusion. At the end of the 7-day treatment, loaded swimming time, organ wet weight and coefficient, serum glucose, urea nitrogen, and hepatic glycogen levels were determined. The outcomes were compared among groups. RESULTS: As compared with the negative: control group, the loaded swimming time was significantly increased in the positive control group, specifically the medium- and high-dose RYD groups (P<0.01). In addition, the wet weights and coefficients of the spleen and thymus, and the serum glucose and hepatic glycogen contents were increased, whereas serum urea nitrogen level was significantly decreased in the positive control group and the high dose RYD group (P<0.05 or P<0.01). CONCLUSION: RYD showed an anti-fatigue effect in mice.

Asunto(s)

RESUMEN

OBJECTIVE: To explore the effect of Renshen Yangrong Decoction (人参养荣汤, RYD) in protecting bone marrow from radiation injury. METHODS: One hundred and eighty Kuming mice were subjected to the three tests for anti-radiation injury effect evaluation, i.e. the test of peripheral white blood cell (WBC) count, the test of bone marrow nucleated cell count, and the bone marrow micronucleus test, using 60 mice for each test. The mice in each test were divided into 6 groups: the blank control group, the model control group, the positive control group treated by Shiyiwei Shenqi Tablet (十一味参芪片, 1.0 g/kg), and three RYD groups treated with high (42.0 g/kg), moderate (21.0 g/kg), and low (10.5 g/kg) doses of crude drugs of RYD, with 10 mice in each group. The treatment was given by gastrogavage perfusion continuously for 7-14 days before mice received (60)Co-γ ray radiation and continued until the end of the experiment. The body weights of the mice were monitored, the changes in peripheral WBC and bone marrow nucleated cells were counted, and the variation in bone marrow micronucleated cells was observed on the respective appointed days. RESULTS: A significant decrease in body weight, peripheral WBC count, and bone marrow nucleated cell count, as well as marked changes in bone marrow micronucleated cells were observed in the mice after radiation, indicating that the radiation injury model was successfully established. As compared with the model control group, the decrease in body weight, peripheral WBC count, and bone marrow nucleated cell count, as well as the increase in bone marrow micronucleus cell count in the high dosage RYD treated group were obviously inhibited or lessened (P<0.05 or P<0.01). CONCLUSION: RYD showed obvious protective effect in mice with bone marrow injury induced by radiation.

Asunto(s)

RESUMEN

OBJECTIVE: To evaluate the efficacy and side effects of combined Chinese drugs and chemotherapy in treating advanced non-small cell lung cancer (NSCLC). METHODS: Sixty-three patients with stage III B and IV NSCLC hospitalized from October 2001 to October 2008 were enrolled and assigned to two groups using a randomizing digital table, with 33 patients in the treatment group and 30 in the control group. They were all treated with the Navelbine and Cisplatin (NP) chemotherapy, but to the treatment group the Chinese drugs Shengmai Injection () by intravenous dripping and Gujin Granule () by oral intake were given additionally. The main observation indexes were response rate (RR), median survival time, 1-year survival rate and median time to progression (TTP); secondary observation indexes were side effects and cycles of chemotherapy. RESULTS: Altogether, 61 patients (33 from the treatment group and 28 from the control group) completed the observation and were assessable. RR was 48.5% (16/33) in the treatment group and 32.2% (9/28) in the control group, and the median survival time were 13 months and 9 months, respectively; the difference between the two groups was significant (P=0.0373 and P=0.014 respectively). However, the differences between groups were insignificant in terms of 1-year survival rate [51.5% (17/33) vs 46.4% (13/28), P=0.4042], median TTP (5.95 months vs 4.64 months, P=0.3242), grade III or IV bone marrow inhibition occurrence rate [33.3% (11/33) vs 39.3% (11/28), P=0.3500], and mean cycles of chemotherapy applied (2.94+/-0.94 cycles vs 2.75+/-0.75 cycles, P=0.4100). CONCLUSION: Combined Chinese drugs and chemotherapy can enhance the short-term therapeutic efficacy in the treatment of NSCLC and prolong patients' median survival time, but show no evident impact on TTP.

Asunto(s)

RESUMEN

OBJECTIVE: To investigate the effect of exogenous phosphatase and tensin homologue deleted on chromosome ten (PTEN) on cell cycle, the expression of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) proteins, and cellular proliferation ability in human pancreas cancer cell line (ASPC-1) exposed to normal oxygen or hypoxia 1% for 24 h were determined. METHODS: ASPC-1 cells were transfected in vitro with an eukaryotic expression plasmid (pEAK8) containing PTEN or not by lipofectin. Positive cell clones were selected, amplified and named ASPC-1-pEAK8-PTEN or ASPC-1-pEAK8 cells. RT-PCR and Western blot were used to determine the target gene expression. PTEN, VEGF and EGFR proteins were assessed by Western blot assay. Cell cycle and the induction of apoptosis were detected by flow cytometry. The tumor growth ability in vivo was assessed in nude mice, and cologenic survival ability was assayed under normal oxygen or hypoxia condition. RESULTS: The expression of PTEN mRNA and protein in ASPC-1-pEAK8-PTEN cells were significantly higher than that in ASPC-1-pEAK8 or ASPC-1 cells. The expression of VEGF protein in ASPC-1-pEAK8-PTEN cells decreased by 23.4%, but EGFR showed no change. The plating efficiency was decreased by 28.0% (F = 4.283, P < 0.05) under normal oxygen condition, compared with those in ASPC-1 cells. The tumor volume in nude mice with ASPC-1-pEAK8-PTEN were significantly different compared to those with ASPC-1 5 weeks after implantation (t = 4.834, P < 0.01). The tumor inhibitory rate was 42.4% in ASPC-1-pEAK8-PTEN group. The expressions of VEGF and EGFR were decreased by 31.4% and 25.0%, respectively. In comparison with ASPC-1 cells, the plating efficiency of ASPC-1-pEAK8-PTEN cells was decreased by 33.2% (F = 9.152, P < 0.01) under hypoxic condition. The cellular apoptosis 8 h after hypoxia and G(2)/M blockage in ASPC-1-pEAK8-PTEN cells were remarkably higher than those in ASPC-1 cells. CONCLUSION: Exogenous PTEN can block ASPC-1 cell cycle at the G(2)/M phase, enhance the cell apoptosis induced by hypoxia, inhibit the expression of VEGF and EGFR proteins under hypoxic condition, and inhibit the proliferation and growth of ASPC-1 cells.

Asunto(s)

Asunto(s)