Biomedical subjects

X Zhou

Publications and source records attributed to X Zhou.

780 records · Page 44Linked to original sources

PubMedDate not supplied

Metabolism of alkyl lysophospholipid in epithelial cancer cell lines and inhibition of cell growth.

The mechanism of inhibition of cancer cell growth by alkyllysophospholipids is not known. We have investigated the metabolism of 1-O-octadecyl-2-O-methylglycerophosphocholine (ET-18-OCH3) in MCF7, A427, and A549 cell lines to determine whether there is a correlation between metabolism and sensitivity and whether the growth-inhibitory effects are due to ET-18-OCH3 or its metabolites. After 12 h incubation with ET-18-OCH3, less than 1.5% of ET-18-OCH3 taken up in the cells was converted to 1-O-octadecyl-2-O-methylglycerol (OMG). No correlation was observed between the extent of metabolism and sensitivity to the compound. Incubation of cells with 1 microgram OMG/mL (2.8 microM) for 12 h resulted in cellular quantities of OMG in MCF7, A427, and A549 that were, respectively, 8-, 5-, and 25-fold greater than those in cells incubated with 5 micrograms ET-18-OCH3/mL (9.6 microM). While 12 h incubation with 1 microgram OMG/mL did not significantly inhibit the proliferation of MCF7 or A427 cells, incubation with 5 micrograms ET-18-OCH3/mL inhibited MCF7 and A427 growth by 90 and 15%, respectively. A549 cell growth was inhibited 10% by 1 microgram OMG/mL, but not by 5 micrograms ET-18-OCH3/mL. Incubation of cells for 12 h with 5 micrograms OMG/mL (13.9 microM) inhibited the growth of all three cell lines. Our results indicate that both ET-18-OCH3 and OMG can inhibit cell growth but the low quantities of OMG produced from ET-18-OCH3 are not responsible for the observed inhibition of MCF7 and A427 cell growth.

Antineoplastic Agents↗

PubMedDate not supplied

The effects of knee reconstruction on combined anterior cruciate ligament and anterolateral capsular deficiencies.

We tested the effect of intraarticular reconstructions of the anterior cruciate ligament alone and in combination with extraarticular reconstructions in 10 cadaveric knees. These knees had anterior cruciate ligament deficiency alone or in combination with anterolateral capsuloligamentous deficiencies. In the knees with combined injury, intraarticular reconstruction returned anterior stability to levels not significantly different from levels found for the knees deficient in the anterior cruciate ligament alone and treated with this procedure. After intraarticular reconstruction, rotational stability of the knee with combined injuries failed to return to the levels seen in the knee with isolated anterior cruciate ligament deficiencies that underwent the same treatment. When a tenodesis with either 0 N or 22 N of tension was added to the intraarticular reconstruction in the knee with combined injuries, we found that excessive internal rotation significantly decreased at all angles of flexion, except at full extension with 0 N of tension. In addition, the extraarticular reconstruction with 22 N of tension in the tenodesis overconstrained the knee in internal rotation between 30 degrees and 90 degrees of knee flexion. The tenodesis with 0 N of tension overconstrained the knee at only 60 degrees and 90 degrees of flexion. These results suggest extraarticular reconstruction as an adjunct to the intraarticular operation for the knee with anterior cruciate ligament and anterolateral structural injuries. The results also suggest that the surgeon can affect anterior and rotational laxity by adjusting the tension in the tenodesis.

Adult↗

PubMedDate not supplied

The cytotoxicity of 1-(1-phenylalkylideneamino)-2,4-azetidinediones and their mode of action in human and murine tumor cells.

The 1-(1-phenylalkylideneamino)-2,4-azetidinediones are potent cytotoxic agents against the growth of human and murine leukemias, lymphoma, and suspended HeLa uterine carcinoma. In cell lines cultured from solid human tumors, the agents were more selective with only a few agents demonstrating significant activity against the growth of HCT-8 ileum adenocarcinoma, Saos-2 osteosarcoma, KB nasopharynx, MCF-7 breast effusion, and ovary 1-A9 carcinoma A mode of action study in murine L1210 lymphoid leukemia cells showed that the agents inhibited DNA and RNA syntheses after 60 min. The compounds were potent inhibitors of the de novo purine synthesis suppressing the activity of both regulatory enzymes of the pathway, i.e., PRPP-amido transferase and IMP dehydrogenase. In addition, the agents reduced the activity of ribonucleotide reductase, dihydrofolate reductase, RNA polymerases, and thymidine kinases as well as the reduction of d[NTP] pools. All of these effects would contribute to the overall reduction of DNA and RNA syntheses. The DNA molecule itself was not a target for the agents in that alkylation of nucleoide bases, intercalation between base pairs, and cross-linking of DNA strands did not occur.

Animals↗

PubMedDate not supplied

The relationship between cellular ether glycerophospholipid content and sensitivity of cancer cells to 1-O-octadecyl-2-O-methyl-glycerophosphocholine.

Cancer cells are more susceptible to the growth-inhibitory effects of alkyl lysophospholipids than normal cells, but the mechanism of this selectivity is unknown. In this study we have investigated the hypothesis that the sensitivity of cells to alkyl lysophospholipids is related to the cellular ether lipid content. The order of decreasing sensitivity of the cells to the growth-inhibitory effect of 1-O-octadecyl-2-O-methyl-glycerophosphocholine (ET-18-OCH3) was MCF 7 > T84 > Malme 3M > A427 > A549, while the order of decreasing ether phospholipid content as a proportion of the total phospholipid was T84 > A427 = A549 = Malme 3M > MCF7. There was also no correlation between ET-18-OCH3-sensitivity and the proportion of ether lipid in the cholineglycerophospholipid or ethanolamineglycerophospholipid classes. Our results clearly indicate that the postulated relationship between ether phospholipid content and ET-18-OCH3-susceptibility may have very limited applicability and is unlikely to be the underlying reason for the selective effects of alkyl lysophospholipids.

Antineoplastic Agents↗

PubMedDate not supplied

Growth suppression of esophageal cancer cells by p16INK4 and p15INK4B in vitro.

PURPOSE: We investigate whether p16INK4 and p15INK4B inhibit cellular proliferation and exert a growth suppressive effect on esophageal cancer cells. MATERIALS AND METHODS: The growth suppressive effects of p16INK4 and p15INK4B were evaluated by transfecting vectors containing the p16INK4 cDNA or the p15INK4B cDNA, or both, constitutively driven by a cytomegalovirus promoter, into two human esophageal cancer cell lines containing or lacking endogenous p16INK4 and/or p15INK4B. RESULTS: These experiments demonstrated that in both cells lines tested, the numbers of cells surviving dramatically decreased in p16INK4-transfected and p15INK4B-transfected cells compared with control vector-transfected cells. There was no significant difference in the degree of growth inhibition between p16INK4-transfected and pI5INK4B-transfected cell lines. CONCLUSIONS: These results suggest that p16INK4 and p15INK4B play important roles in the initiation or promotion of esophageal cancer. The inactivation of p16INK4 and p15INK4B may contribute to uncontrolled growth in human cancer.

Carcinoma, Squamous Cell↗

PubMedDate not supplied

Mechanism of dipeptide stimulation of its own transport in a human intestinal cell line.

The initial objective of this study was to investigate whether the presence of dipeptide in the culture medium stimulates the uptake of dipeptide by a human intestinal cell line that expresses the oligopeptide transporter (Pept-1). The results showed that addition of glycylsarcosine (Gly-Sar) for 24 hr to the culture medium significantly increased the rate of glycylglutamine (Gly-Gln) uptake by Caco-2 cells. Furthermore, this stimulation in transport was also observed when Cefadroxil (beta-lactam antibiotic) instead of Gly-Gln was used as a probe but did not occur when Gly-Sar was added to the culture medium for only 2 hr or when Gly-Sar was substituted by a corresponding mixture of glycine plus sarcosine. The subsequent objective of the study was to investigate the mechanism of stimulation in transport described earlier. The results showed that the addition of Gly-Sar for 24 hr to the culture medium: (1) increased the Vmax of Gly-Gln transport by two-fold without affecting its Km, (2) increased the protein mass of Pept-1 by more than two-fold, (3) increased the abundance of Pept-1 mRNA by three-fold, and (4) had no effect on Gly-Gln transport when an inhibitor of trans-Golgi network (brefeldin) was added to the culture medium, but still increased the abundance of Pept-1 mRNA. In conclusion, the results show that dipeptides stimulate their own transport by increasing the membrane population of Pept-1. The molecular mechanism appears to be an increase in expression of the gene encoding Pept-1. A therapeutic application of the present results is that if bioavailability of orally administered peptidomimetic drugs is limited, patients may be tried on a high-protein diet to enhance their absorption.

Biological Transport, Active↗