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K J Scanlon

Publications and source records attributed to K J Scanlon.

79 records · Page 5Linked to original sources
PubMedDate not supplied

Dihydrofolate reductase gene expression characterized by the PCR assay in human leukemia cells.

A modified enzymatic amplification (PCR) method has been used to detect overexpression of the dihydrofolate reductase gene in human leukemic cells resistant to methotrexate (MTX) from both patient samples and cell lines in culture. Quantitation of DHFR mRNA by the PCR assay has been demonstrated to be more accurate and more sensitive than Northern blotting. This assay be useful in screening patients relapsing with drug resistance.

Base Sequence↗
PubMedDate not supplied

Evaluation of N-4-(hydroxycarbophenyl) retinamide as a cancer prevention agent and as a cancer chemotherapeutic agent.

In this review, a retinoid analogue (N-4-hydroxycarbophenyl) retinamide (R11) has been evaluated for its pharmacological and clinical properties. R11 has been studied both as a cancer prevention agent, as well as, a cancer chemotherapeutic agent. R11 alone and in combination with other agents can be used for the treatment of cervical dysplasia or leukemia. This review will examine novel strategies and mechanisms of action for retinoids in the treatment and prevention of cancer.

Animals↗
PubMedDate not supplied

Molecular basis of cisplatin resistance in human carcinomas: model systems and patients.

In this review, cisplatin resistance will be summarized. We will discuss characteristics of potential mechanisms of resistance in tissues from patients with ovarian, colon and breast carcinoma. Secondly, a new molecular biology assay will be discussed which detects changes in gene expression in cisplatin-resistant cells. Finally, based on the biochemical and molecular properties of cisplatin-resistant tumors, new strategies to exploit or circumvent cisplatin resistance in human tumors will be entertained.

Cisplatin↗
PubMedDate not supplied

Inhibition of methionine transport by methotrexate in mitogen-stimulated human lymphocytes.

Mitogen stimulation of human lymphocytes was used to study the expression of several amino acid transport systems in response to cell growth. Resting lymphocytes possess detectable neutral amino acid transport systems which can be activated by the mitogen, phytohemagglutinin (PHA). Sodium-independent transport of 2-aminobicyclo (2,2,1) heptane 2-carboxylic acid was similar in resting and stimulated lymphocytes. However, sodium-dependent uptake of methyl aminoisobutyric acid and alpha-aminoisobutyric acid increased threefold to eightfold with stimulation by PHA. Methionine uptake was primarily sodium-independent in resting lymphocytes, whereas methionine uptake increased fourfold to eightfold in stimulated cells; most of this increase was attributable to sodium-dependent transport. Uptake of methotrexate (MTX) was minimal in resting lymphocytes but was maximal 72 hrs after stimulation with PHA; this increase in MTX uptake was accompanied by inhibition of sodium-dependent methionine transport. These results suggest that PHA activates sodium-dependent transport of methionine and that this activation is blocked by the folate antagonist, MTX.

Biological Transport↗
PubMedDate not supplied

Suppression of EJ cells tumorigenicity.

Ribozymes, site-specific ribonucleases, are a new vehicle for the manipulation of gene expression. A hammerhead ribozyme designed to cleave the GUC sequence in codon 12 of activated H-ras RNA was cloned into a plasmid (pH beta Apr-1) and transfected into EJ human bladder carcinoma cells. Expression of the ribozyme dramatically reduced H-ras gene expression and inhibited growth of EJ transformants in vitro. In vivo, the H-ras ribozyme suppressed EJ cell tumorigenicity in nude mice. In contrast, the insertion of a mutant ribozyme with no demonstrable cleavage capacity into EJ cells resulted in smaller reductions in H-ras gene expression and growth inhibition while also suppressing tumorigenicity in nude mice. The ribozyme's effect on tumorigenicity was stable, as the cells were cultured for up to five months in vitro prior to injection into nude mice. These studies define a role for anti-oncogenic ribozymes as a unique class of tumor suppressing agents.

Animals↗
PubMedDate not supplied

Reversal of cisplatin resistance in vivo by an anti-fos ribozyme.

Human colon cancer cells, SW480DDP and SW620DDP, which express fos gene highly, are resistant to cisplatin treatment. We prepared a hammerhead ribozyme to selectively cleave fos mRNA and revealed that the for ribozyme significantly suppressed the expression of fos gene in resistant cells in vitro. The fos ribozyme which was transfected into the implanted tumor cells resistant to cisplatin, had also the ability to reduce the expression of fos gene in vivo, and reversed cell sensitivity to cisplatin. These results reinforce the potential role of anti-oncogene ribozymes in dealing with the problem of drug resistance, with new possible implications for gene targeting therapy.

Antineoplastic Agents↗