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Li Li

Publications and source records attributed to Li Li.

At least 433 records · Page 24Linked to original sources
PubMed2004

Involvement of base excision repair in response to therapy targeted at thymidylate synthase.

Thymidylate synthase (TS) is an important target of several classes of chemotherapeutic agents. Although the precise mechanism of cytotoxicity in thymidylate deprivation remains obscure, uracil misincorporation and DNA strand breaks are recognized as important events during thymidylate deprivation. Base excision repair (BER) plays a primary role in removing damaged or modified bases from the genome, including uracil. Because of uracil misincorporation, BER is hypothesized to play a role in the cellular response to thymidylate deprivation. In this study, we used murine embryo fibroblasts wild-type or homozygous null for DNA polymerase beta (beta-pol), which plays a central role in BER. We found that, compared with wild-type, beta-pol null cells were resistant to the toxic effects of raltitrexed (Tomudex, ZD1694), a folate inhibitor of TS. There was little difference in TS levels or in TS-ligand complex formation between the cell lines. Furthermore, cells deficient in XRCC1, a scaffold protein for the final steps of BER, were also modestly resistant to raltitrexed compared with XRCC1-proficient cells. Cell cycle analysis revealed that the responses of the wild-type and beta-pol null cells were similar during drug exposure. However, following drug removal, the beta-pol null cells appeared to resume cell cycle progression more rapidly than the wild-type cells. The results suggest that BER plays a role in modulating the toxic effects of TS inhibitors, and that this role occurs during recovery from TS inhibition.

Animals↗
PubMed2004

Development and characterization of five cell models for chemoresistance studies of human ovarian carcinoma.

Platinum agents and paclitaxel (taxol) are among the most effective drugs currently available for treatment of ovarian cancer. One of the hurdles with taxol and platinum- based therapy is the clinical development of resistance to these agents. To investigate the mechanism of drug resistance in human ovarian cancer, we developed and characterized 5 cell models for chemoresistance studies of cisplatin, carboplatin and taxol. We report in this study that these human ovarian carcinoma cell model systems include 2 models for cisplatin resistance, 2 models for carboplatin resistance, and 1 model for taxol resistance. The biological and biochemical characteristics of the models showed that (i), the IC50 values of the drugs for all these resistant cell models were 3 times (or more) higher than those for the parental tumor cells. There also exist varying degrees of cross-resistance to several other chemotherapeutic agents in these systems. Moreover, the intracellular drug accumulations in these cells were significantly reduced as compared to those in the parental cells. (ii), The proliferation rates of these resistant cells were markedly decreased. However, there were no obvious changes in cell cycle distribution in these model systems. (iii), Our results for the expression of a few major drug resistance-related genes revealed that the expression of p53, lrp-1 and mrp-1 was decreased, while the expression of pkc, topo I and topo II beta was increased in the resistant tumor cells as compared with the parental cells. In contrast, no significant alterations in gst-pi and topo II alpha expression were found. Interestingly, the levels of mdr-1 expression were elevated in some models, but were reduced in others, thus suggesting that different pathways are involved in the formation of drug resistance in different cell model systems, and that different mechanisms are responsible for the development of different drug resistances in tumor cells. Taken together, our findings indicate that these models may be potentially used to assess the biochemical and genetic mechanisms of drug resistance in human ovarian cancer and to identify new drug resistance-related genes.

Antineoplastic Agents↗
PubMed2004

[Protective and therapeutic effect of pulmonary surfactant on the experimental chronic obstructive pulmonary disease in hamsters].

OBJECTIVE: To investigate the protective and therapeutic effects of pulmonary surfactant in the pathogenesis of chronic obstructive pulmonary disease (COPD) in hamsters. METHODS: COPD animal model was established by smoke inhalations and intratracheal instillations of pancreatic elastase in hamsters. Ninty hamsters were divided into 9 groups as follows: normal group (N), two groups received smoke inhalations for 1 and 3 months (S1 and S3), one group received intratracheal instillation of surfactant (10 mg/100 g BW) for once after 1 month smoking (SP1), one group was treated with surfactant after 1.5, 2 and 2.5 months of smoking (SP3), and two groups received intratracheal administration of elastase (40 U/100 g BW) and were killed after 1 month and 3 months, respectively (E1 and E3). The surfactant was injected intratracheally after 1 week, 0.5, 1.0, 1.5, 2.0, and 2.5 months, followed by administration with elastase (EP1 and EP3). EP1 group were killed at the first month, and EP3 at the third month. Light microscopy and electromicroscopy observations were performed in each group. Pulmonary mean linear intercept (MLI), mean alveolar numbers (MAN), and pulmonary alveolar area (PAA) was measured by image analysis. The expression of surfactant protein A (SP-A) were observed by immunohistochemistry. RESULTS: Smoking for 3 months and instillations of elastase resulted in chronic bronchitis and emphysema. MLI and PAA increased and MAN decreased in all the experimental groups compared with in the normal group (P < 0.05 or P < 0.01). Administration of surfactant for 3 months resulted in statistically significant inhibition of pulmonary injury. MLI and PAA decreased and MAN increased in SP3 compared with in S3. Only MLI decreased in EP3 compared with E3. The expressions of SP-A in the type II alveolar epithelia decreased in S3 and E3 (compared with the normal group P < 0.01). After pulmonary surfactant intervention, the expression of SP-A increased significantly. CONCLUSION: Pulmonary surfactant may have a long-term protective effect on chronic smoking and elastase-induced COPD.

Animals↗
PubMed2004

Relationship between methylenetetrahydrofolate reductase C677T and A1298C genotypes and haplotypes and prostate cancer risk and aggressiveness.

Previous reports indicate that polymorphisms in the MTHFR gene play a role in cancer development, but their potential impact on prostate cancer has not been well studied. Here, we evaluate the association between two MTHFR polymorphisms, C677T and A1298C, and prostate cancer risk and aggressiveness in a moderately large family-based case-control study (439 cases and 479 sibling controls). Among all study subjects, we observed no association between the C677T variant and prostate cancer but a slight positive association between the A1298C variant and risk of this disease [odds ratio (OR) 1.41, 95% confidence interval (CI) 0.96-2.06; P = 0.08]. When stratifying the study population by disease aggressiveness at diagnosis, the C677T variant was positively associated with risk among men with less advanced disease (OR 1.86, 95% CI 1.00-3.46; P = 0.05). In contrast, when looking at men with more advanced disease, the C677T variant was inversely associated with risk (OR 0.51, 95% CI 0.32-0.82; P = 0.01), whereas the A1298C variant was positively associated with risk (OR 1.79, 95% CI 1.06-3.02; P = 0.03). Furthermore, the 677T-1298A haplotype was positively associated with prostate cancer among men with less advanced disease (OR 1.84, 95% CI 1.07-3.16; P = 0.03) and inversely associated with risk of more advanced disease (OR 0.47, 95% CI 0.29-0.76; P = 0.002). Our findings suggest that 677T and 1298A, or another variant on their haplotype, may be associated with a reduced risk of progression to more advanced prostate cancer.

Adult↗
PubMed2004

[Research on the application feasibility of HLA-DRB1 genotyping for forensic identification by oligonucleotide chip].

OBJECTIVE: Research on the application feasibility of HLA-DRB1 genotyping for forensic identification by oligonucleotide chip. METHODS: Population studies on HLA-DRB1 was carried out in a sample of 561 unrelated Chinese Han individuals using oligonucleotide arrays for genotype detection. Meanwhile, we explored the feasibility of typing HLA-DRB1 by DNA chip for forensic identification. RESULTS: No significant deviations from Hardy-Weinberg equilibrium could be found. The Observed heterozygosity(Ho) was 0.888. The Expected heterozygosity (He) was 0.902. The Polymorphic information content (PIC) was 0.893. The Average exclusion probability (PE) was 0.801. Pedigree analysis showed no deviation from Mendel's Law. CONCLUSION: The data and results of pedigree analysis and case application demonstrated that HLA-DRB1 typing by oligonucleotide probe arrays was a useful technique for paternity testing and individual identification.

Alleles↗
PubMed2004

[Establishment of 5 resistant ovarian cancer cell strains and expression of resistance-related genes].

OBJECTIVE: To investigate expression difference of several drug resistance related genes between sensitive and resistant ovarian carcinoma cells. METHODS: Cell lines resistant to cisplatin, carboplatin and taxol were established from ovarian carcinoma cell lines of SKOV3 and A2780, and their biological features were detected. The expressions of several genes related to drug resistance were measured by RT-PCR method. RESULTS: (1) The values of resistance index (RI) of resistant cells to relevant drugs were elevated 3 times or more, with different degrees of cross-resistance to several other drugs (RI 2 approximately 20). They grew more slowly than primary cells (Td elongated 1.4 approximately 2.4 times, P < 0.01) without obvious changes in G(1), G(2), and S ratios (P > 0.05). Intracellular concentrations of relevant drugs were reduced 2.0 approximately 8.5 times in resistant cells (P < 0.05). (2) p53, lung resistance protein-1 (LRP-1), multiple drug resistance related protein-1 (MRP-1) genes were expressed at lower levels in resistant cells than in sensitive cells; while protein kinase C (PKC), topoisomerase (topo) I, and topo II beta were expressed higher, no obvious alterations were found concerning glutathione S transferase-pi (GST-pi), and topo II alpha. Expression of multiple drug resistance-1 (MDR-1) gene was either elevated or reduced in different cells. CONCLUSIONS: The expressions of resistance related genes were widely different in different kinds of resistant cells, suggesting more than one pathway leading to resistance transformation. This adds more difficulties for clinical management.

Carboplatin↗
PubMed2004

[Synthesis and application of the polyacrylamide beads acting as LDL adsorbent's matrices].

This study in pursuit of the synthetic technologies and structure characterization of polyacrylamide-based matrices (PAM beads) for low density lipoprotein (LDL) adsorbent and their adsorbability for LDL was intended for an experimental evidence of developing advanced matrices for LDL adsorbent. PAM beads were synthesized by inverse suspension polymerization, and their structure characterization was characterized by SEM, image analyzer and small angle X-ray scattering. The tripeptide serine-aspartic-glutamic acid (SDE) was coupled on the PAM beads to prepare the LDL adsorbents whose adsorbability for LDL was determined in vitro. The results showed that the PAM beads with the average size diameter 142.1 microm and the average pore diameter 119.8 nm could act as the matrices in accordance with the requirement of adsorbent for LDL. When the amount of acrylamide and the crosslinking agent N,N'-methylene-bis(acrylamide) was fixed, the average pore diameter decreased with the increase of the crosslinking agent content. Although the nonspecific binding of PAM beads for LDL was low, they could selectively adsorb LDL after coupling the SDE on the PAM beads.

Acrylic Resins↗
PubMed2004

[Enhancing antitumor activity of tumor-draining lymph node cells by autologous dendritic cells].

AIM: To enhance antitumor activity of tumor-draining lymph node(TDLN) cells by autologous dendritic cells(DCs) in-vitro. METHODS: Peripheral blood mononuclear cells(PBMCs) were isolated from the patients with gastric adenocarcinoma and induced with GM-CSF, IL-4 and TNF-alpha to obtain mature DCs which were then sensitized by autologous tumor lysate. TDLN cells were isolated and purified from lymph nodes of the patients and incubated with IL-2. Then we designed three experiment groups: (1)first group: TDLN cells activated by sensitized DCs; (2) second group:TDLN cells activated by autologous tumor lysate; (3)third group: TDLN cells alone, which were used as control. Cytotoxic activity of TDLN cells to gastric adenocarcinoma cell line KATO3 and human melanoma cell line A375 were compared between 3 groups. RESULTS: The cytotoxicity of TDLN cells activated by sensitized DCs to KATO3 cells was significantly stronger than that of TDLN cells activated by autologous tumor lysate or TDLN cells alone. In contrast, for A375 cells, cytotoxic activities of three TDLN cells had no significant difference. CONCLUSION: Specific antitumor activity of TDLN cells can be enhanced significantly by activated autologous DCs.

Adenocarcinoma↗
PubMed2004

[Mesorectal spread and circumferential margin involvement of rectal cancer studied on large slice].

OBJECTIVE: To provide the mode of cancer distribution in the mesorectum and circumferential resection margin. METHODS: Large slice technique was used in the pathologic study of 62 specimens operated on following the principles of total mesorectal excision (TME). RESULTS: More than 40% of all the observed neoplastic foci were located in the outer layer of the mesorectum in Stage III patients. Further analysis of the foci's localities with respect to the primary tumor's locality showed that ipsolateral neoplastic foci (44.44%) were significantly more than the contralateral neoplastic foci (13.33%) in the mesorectum (P<0.05). Extramural distal spread was found in 8 cases with the maximum extent of 3.5 cm. No significant difference in occurrence of circumferential margin involvement (CMI) was observed among tumors of different location, but tumors of poorer differentiation were noted to have a higher risk of CMI. CONCLUSION: Large slice technique offers a whole image of rectum, mesorectum, together with the position of neoplastic foci. There are outer preponderance and lateral discrepancy of neoplastic foci distribution in the mesorectum. A distal clearance margin of 4 cm would be mandatory. We advocate the adoption of TME as the baisc surgical principles in treating patients with rectal cancer and in avoiding surgery-related circumferential margin involvement.

Adenocarcinoma↗
PubMed2004

[Expression of matrix metalloproteinases-9,2,7,and tissue inhibitor of metalloproteinases-1,2,3 mRNA in ovarian tumors and their clinical significance].

BACKGROUND & OBJECTIVE: Matrix metalloproteinases (MMPs)play an important role in cancer cell invasion,and metastasis by degrading the extracellular matrix (ECM). The activities of MMPs are regulated by tissue inhibitor of metalloproteinases (TIMPs). This study was to detect mRNA expression of MMP-9, 2, 7, and TIMP-1, 2, 3 in ovarian tumor tissues,and explore their correlations with clinicopathologic characteristics,and prognosis of patients with ovarian cancer. METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR)was used to assay the positive rates,and half-quantity values of MMP-9, 2, 7, and TIMP-1, 2, 3 mRNA in 48 cases of malignant ovarian tumor tissues, 21 cases of benign ovarian tumor tissues, and 22 cases of normal ovarian tissues. RESULTS: The positive rate of MMP-9 mRNA, and the half-quantity values of MMP-9,MMP-2 were significantly higher in malignant tumor tissues than those in normal ovarian tissues (P< 0.05). The positive rates and half-quantity values of TIMP-2,MMP-7,TIMP-3 mRNA were significantly higher in malignant and benign ovarian tumor tissues than those in normal ovarian tissues (P< 0.05). The ratio of MMP-9/TIMP-1 was higher in malignant ovarian tumor tissues(0.91+/-0.67) than that in normal ovarian tissues (0.14+/-0.33)(P< 0.05). The expression level of MMP-9 mRNA was higher in ovarian cancer tissues of stage III-IV(1.13+/-0.66) than those of stage I-II(0.60+/-0.54)(P< 0.05). The mean survival time of MMP-9 positive patients was (43.00+/-17.12) months,and cumulate survival rate was 47.37%,significantly lower than that of MMP-9 negative patients (100%). CONCLUSIONS: MMP-9, MMP-2, MMP-7, TIMP-2, TIMP-3 are over-expressed in ovarian malignant tissues. The over-expression of MMP-9, and the imbalance between MMP-9 and TIMP-1 play important roles in the progress of advanced ovarian cancer. MMP-9 may be a useful prognostic marker for patients with advanced ovarian cancer.

Adolescent↗
PubMed2004

[Study on the expression and mutation of cadherin 6 gene in human ovarian carcinoma].

OBJECTIVE: To study expression and mutation of cadherin 6 gene in human ovarian tumor tissues and its clinical significance and to explore new molecular biomarker of ovarian tumors. METHODS: The expression and mutation of cadherin 6 in 41 cases of malignant ovarian tumors, 15 cases of benign ovarian tumors and borderline ovarian tumors and 17 cases of normal tissues were detected by RT-PCR and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique respectively. RESULTS: The positive expression rates of cadherin 6 were 71% in normal group, 53% in benign ovarian tumors, 24% in malignant ovarian tumors, being significantly higher in the former two groups than in malignant tumor group (P < 0.05). Statistical analysis revealed a significant correlation between cadherin 6 gene expression and clinical stages and histological subtype of malignant ovarian tumors. Lower expression rate of cadherin 6 gene was found in cancer tissues at stages III approximately IV than at stages I approximately II (P < 0.01). No mutation was found in normal group and benign tumor tissues and it was observed in 2 out of 41 malignant ovarian tumor tissues. CONCLUSIONS: These results suggest that expression of cadherin 6 gene tends to lack in advanced ovarian carcinoma with lymph node metastases, as well as in poorly differentiated carcinomas. It may be a prognostic marker of ovarian carcinoma.

Cadherins↗
PubMed2004

[Studies on quality standards of radix Angelicae dahuricae].

OBJECTIVE: To work out a qualitay standard of Radix Angelicae dahuricae. METHOD: TLC and HPLC were adopted. RESULT: Four coumerin compounds were identified by TLC, and the contents of two compounds were determined by HPLC. CONCLUSION: Imperatorin, isoimperatorin, byakangelicin and oxypeucedaninhydrate can be found simultaneously in Radix Angelicae dahuricae. The contents of imperatorin and isoimperitorin are not lower than 0.1% and 0.04% respectively.

Angelica↗