Search

This paper gave a brief introduction of the effect of Solanum nigrum on anti-cancer. The experimental results showed that the total alkaloid isolated from S. nigrum interfered structure and function of tumor cell membrane, disturbed the synthesis of DNA and RNA, changed the cell cycle distribution, so that total alkaloids could play in inhibabition to tumor cells, while the glycoprotein (150 x 10(3)) isolated from S. nigrum might have shown anti-cancer abilities by blocking the anti-apoptotic pathway of NF-kappaB, activating caspase cascades reaction and increasing the production of nitric oxide.

Objective: To detect the expression levels of telomere binding factor 2 (TRF2) mRNA in tumor tissue of non-Hodgkin lymphoma (NHL) patients using quantitative real-time RT-PCR., Methods: The target gene mRNA was amplified with RT-PCR, then was sequentially electrophoresed and purified as standards, and the standard curves of gene expression were established. The expression levels of TRF2 mRNA of lymphoid tissue from NHL and reactive lymphoadenopathy were detected with real-time RT-PCR., Results: The correlation coefficient was 0.996 between the amount of template cDNA and the intensity of fluorescence signal when gene expression standard curves were established. The correlation coefficient of template cDNA amount and grey density of bands derived from gel electrophoresis of real-time RT-PCR final products was 0.779 (P<0.05). Of all NHL patients, expression levels of TRF2 mRNA of follicular lymphoma, mantle cell lymphoma and diffuse large B cell lymphoma were(22.943 +/-9.424) amol, (23.181 +/-5.983) amol and (18.339 +/-7.910) amol, respectively, which had no significant difference compared with reactive lymphoadenopathy [(21.796 +/-4.800) amol, P>0.05]. The expression level of TRF2 mRNA of Burkitt lymphoma was (33.170 +/-12.841) amol, which was significantly higher than that of reactive lymphoadenopathy and other types of NHL (P<0.05)., Conclusion: Alcohol drinking isn't one of the risk factors of colorectal cancer among Jiashan County population.

Objectives: To explore the significance of PTEN (phosphatase and tensin homolog deleted on chromosome 10) in the development of human primary hepatocellular carcinoma (HCC)., Methods: PTEN protein expression in cancerous liver tissues and paired para-carcinoma liver tissues from 60 HCC patients was detected by immunohistochemistry and PTEN mRNA expression was analyzed by northern blot. The significance of PTEN in the development of HCC was analyzed by investigating the relationship between the expression levels of PTEN protein and mRNA, and the clinicopathological parameters of HCC patients., Results: PTEN protein was immunohistochemically stained in the cytoplasmic region of para-carcinoma liver tissues in all the 60 patients, while only 48.3% (29/60) of the patients were positive for PTEN protein in cancerous liver tissues. The positive rate of PTEN protein in HCC tissues were relative to the histological gading and the presence of tumor thrombus. In grade I - II, III, and IV, the positive rates were 84.0%, 23.8%, and 21.4% respectively, and in the group with tumor thrombus was 26.7%, while in the group without tumor thrombus was 55.6%. Northern blot showed that there existed four PTEN mRNA transcripts with the length of 5.5kb, 4.4kb, 2.4kb, and 1.8kb respectively. The level of PTEN mRNA expression in HCC tissues was much lower than that in the paired para-carcinoma liver tissues. The low expression level of the 5.5kb and 4.4kb transcripts was significantly associated with serum AFP value, presence of tumor thrombus, state of satellite lesion and histological grading. The low expression level of the 2.4kb transcript in HCC was significantly associated with the presence of tumor thrombus and satellite lesions in HCC patients. However, no evident relationship between the lowered expression level of the 1.8kb transcript and the clinicopathological parameters of HCC was observed in these 60 patients., Conclusions: Down-regulation of PTEN expression may play an important role in the development of HCC and the expression level of PTEN may be a potential adjuvant parameter in forecasting the progress and prognosis of HCC.

Howiinol(GHM-10), a new compound isolated from Goniothalamus howii, had been shown to have marked anticancer activity both in vitro and in vivo. In the present study, the effect of GHM-10 on the biosynthesis of macromolecules in L1210 cells was investigated. By using [3H] labeled precursor incorporation assays, we found that the biosyntheses, of DNA, RNA and protein in L1210 cells were inhibited markedly after the cells were pretreated with GHM-10 in 4-12 micrograms.ml-1 for 6 h and the inhibition of DNA synthesis was the most obvious one. We also used the methods of [3H]TdR incorporation curve, shift of UV-absorption spectrum and shift of fluorescence spectrum to investigate the mechanism of inhibitory action of GHM-10 on DNA biosynthesis. The results showed that the inhibition of DNA synthesis already became irreversible after the L1210 cells were treated with GHM-10 in 6-8 micrograms.ml-1 for 1 h, indicating that GHM-10 may induce damage on DNA molecular structure. However, when calf thymus DNA was treated with GHM-10, the UV-absorption spectrum and the fluorescence spectrum of the DNA were not changed significantly. It is suggested that GHM-10 was not able to intercalate into DNA molecules or to damage the structure of DNA directly.

The recombinant plasmid PGC was constructed for transcription unit of c-myc gene with bi-direction in vitro, to make RNA probes for detection of c-myc mRNA and antisense RNA expression of transfectant HLR60-9, which was obtained from HL60 cells transfected with inducible c-myc antisense RNA expression plasmid. The results from HLR60-9 cells induced by Cd2+ indicated that expression of c-myc antisense RNA increased with Cd2+ concentration and exposure time, while c-myc mRNA expression progressively reduced. Using immunohistochemical technique no c-myc P62 protein expression was detected. The incorporation of 3H-TdR,3H-UR,3H-Leu revealed significant suppression of DNA, RNA and protein biosyntheses. It is suggested that the reversion changes previously reported in malignant phenotypes of HLR60-9 cells and the inhibition of macromolecule biosynthesis mentioned above were associated with the blockade of c-myc gene expression by its antisense RNA.

A recombinant retroviral vector expressing antisense Ki-ras was constructed. The recombinant virus DNA was packaged with packaging cell line PA317 cells by the calcium phosphate coprecipitation method. The virus supernatant was used to infect human pancreatic carcinoma cell line PC-2. After selection with Puromycin, resistant colonies were obtained. Stable expressions of retrovirus in both PA317 and PC-2 cells were exhibited by Northern blot hybridization. A down regulation of endogenous Ki-ras was found in PC-2 cells infected with antisense Ki-ras construct. It was demonstrated that the antisense Ki-ras did inhibit the cell growth rate and 3H-TdR incorporation rate of PC-2 cells. The ability of colony formation in soft agar and tumorogenicity in nude mice of PC-2 cells were significantly suppressed by the antisense Ki-ras. The results implicate that recombinant retroviral vector containing antisense Ki-ras could inhibit target gene expression and partly reverse malignant phenotype of pancreatic adenocarcinoma cells.

A fluorouracil (FU)-resistant human carcinoma cell line (SGC-7901/R) was established in culture by progressively increasing the concentration of FU from 50 ng.ml-1 to 2.5 mg.ml-1. The cell line has been successfully subcultured for more than 150 passages during more than 2 years. Its degree of FU resistance was 139-fold vs that of FU sensitive cell line (SGC-7901/S), and the resistant phenotype was stable when cells were cultured for 23 passages in FU-free medium. The doubling time was 17.3 and 25.6 h for resistant cells and parental cells, respectively. Swiss (nu/nu) nude mice were used for the in vivo experiment, the FU-resistant cell line also exhibited resistance to FU and cross-resistance to mitomycin C. FU inhibited markedly the incorporation of [3H]UR into sensitive cells and only showed a 31.6% inhibition with FU 100 micrograms.ml-1 in resistant cells. For the incorporation of [3H]TdR into DNA, inhibitory rates were seen with different concentrations of FU in resistant cells. By morphologic observation, SGC-7901/R cells showed little secretion but without any tendency to glandular pattern. Their nuclei were allotype with enlarged perinuclear space and a few intranuclear pseudoinclusions. The mitotic phase of cells was found frequently. The phenotype of resistant cell line can be deduced more malignant than that of parental cell line.

Beta-carotene at concentration of 6.25 micrograms/ml was shown to inhibit significantly the colony forming efficiency (CFE) of cultured human lung cancer 801 cell line and at 12.5 micrograms/ml was shown to completely inhibit CFE. A 42%-68% (P < 0.01) decrease in spontaneous lung metastasis of LA795 murine pulmonary adenocarcinoma was observed when T739 inbred strain mice were fed a diet with beta-carotene (25mg/100g diet). Ability of DNA and RNA synthesis of lung cancer cells were decreased (P < 0.05) after treating with beta-carotene (25 micrograms/ml) by 24 hours, but the ability for DNA synthesis of human lymphocytes was not effected by the same treatment. Expression of ras oncogene was proved to be inhibited by beta-carotene because the product of ras p21 proteins of cancer cells was decreased after treating by beta-carotene.

By means of nuclide precursor incorporation, the effects of 211At labelled monoclonal antibody against gastric cancer (211At-3H11McAb) on DNA, RNA and protein synthesis in gastric cancer cell were studied. The results show that 211At-3H11McAb and Na211At-3 inhibit 3H-TdR, 3H-UR and 3H-Leu incorporation, especially 3H-UR incorporation, into gastric cancer cell at 3.7 x 10(4)Bq and 1.85 x 10(5)Bq; the inhibiting rates depend on concentration. The DNA biosynthesis in gastric cancer cell gradually recover after the drug is removed, suggesting that the drug should exert an inhibiting action on DNA biosynthesis in tumor cell through interference of DNA metabolism.

The antitumor activity of GP-7, a new spin-labeled epipodophyllotoxin, was studied by liquid scintillation spectrometry. There were many similarities between GP-7 and etoposide. Both GP-7 and etoposide inhibited the incorporation of [3H]TdR, [3H]UR, and [3H]Leu into DNA, RNA, and protein synthesis in leukemia 7712 cells. The inhibition correlated with drug concentration and duration. IC50 of GP-7 and etoposide on DNA synthesis at 24 h were 0.21 and 0.37 micrograms.ml-1, respectively. The inhibition of GP-7 or etoposide on DNA synthesis retained even after the drug were washed out for 3 h. GP-7 and etoposide caused DNA single-strand breaks, with a well concentration-response relationship. These data suggest that the inhibition of DNA synthesis by GP-7 or etoposide is likely due to the damage of DNA template and breaking of single-strand DNA.

Five compounds were isolated from the seeds of Momordica charantia. This paper reports their structure determination by spectral (IR, UV, HNMR, CNMR, and MS) and chemical methods. The structures of I, II, III, IV and V were elucidated as vacine, mycose, 3-O-(beta-D-glucopyranosyl)-24 beta-ethyl-5 alpha-cholesta-7, trans-22E, 25 (27)-trien-3 beta-ol, momorcharaside A and momorcharaside B respectively. Mycose was the first time found in this plant and compound III was the first time found in the genus Momordica. IV and V were new compounds. IV exhibited obvious inhibition of DNA and RNA syntheses in S 180 tumor cells in preliminary pharmacological studies.

Podophyllic acid piperidyl hydrazone nitroxide radical (GP-1) and etoposide (VP-16), derivatives of podophyllotoxin, inhibited DNA, RNA, protein and ATP synthesis of leukemia L7712 cells at a concentration of 5 micrograms/ml. Inhibitory extents were dependent on the exposure time from 3 to 24 h. The inhibitory rates of both drugs were about 15-66%. ID50 of GP-1 and VP-16 on the synthesis of L7712 cells at 24 h were 0.16 and 0.38 micrograms/ml, respectively. The dose-response curve of GP-1 was a parabolic one, while that of VP-16 was a straight line. The inhibition of GP-1 or VP-16 on DNA synthesis existed also after cells washing. It is suggested that the antitumor effects of GP-1 and VP-16 seem to be related to the damage of DNA template.

Methyl, n-butyl 2'-TBDMS-N2-DMF-guanosine 3',5'-cyclic phosphate and 2'-TBDMS-N2-DMF-guanosine 3',5'-cyclic diethyl-phosphoramidate were synthesized by reaction of protected guanosine with trivalent phosphorus reagents in the presence of tetrazole followed by oxidation. The reaction occurred stereospecifically. Protected guanosine 3',5'-cyclic phosphotriesters and N, N'-diethyl-phosphoramidate were shown to have inhibitory activity on the synthesis of DNA and RNA in mouse liver tumor cell. Diastereoisomers of n-butyl N2-substituted guanosine 3',5'-cyclic phosphate have been shown to activate adenylate cyclase in vitro.

The incorporations of [3H] thymidine, [3H]uridine and [3H]leucine into DNA, RNA and protein synthesis in leukemia 7712 cells were inhibited by the complex of 3,6-di-(dimethylamino)-dibenzopyriodonium with praseodymium (Pr, rare earth element) dicitrite 34 micrograms/ml for 3-24 h. The degree of inhibition increased in proportion to the incubation time. After being treated with [C17H20N2I]3[Pr(C6H5O7)2] 34 micrograms/ml for 3, 6, 12 and 24 h, the incorporation of [32P]Na2HPO4 into the nucleoprotein of leukemia 7712 cells was inhibited by 49, 57, 65 and 85%, while those into ATP were inhibited by 43, 59, 65 and 83%, respectively. The ID50 of [C17H20N2I]3[Pr(C6H5O7)2] on DNA synthesis in leukemia 7712 cells at 24 h was 22 micrograms/ml. After the complex was removed from the medium entirely, the rate of DNA synthesis decreased with time over 3-12 h. This result indicated that the inhibition mechanism was likely due to damage to the DNA template.