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M Clynes

Publications and source records attributed to M Clynes.

64 records · Page 4Linked to original sources

Membrane changes associated with the early stages of apoptosis in HEp-2 cells decrease susceptibility to adherence by Candida albicans.

The aim of the present work was to establish whether apoptotic HEp-2 cells demonstrated an altered susceptibility to adherence by the pathogenic yeast Candida albicans. Cultures of HEp-2 cells were treated with concentrations of three chemotherapeutic agents sufficient to induce cell death by apoptosis and this was confirmed by microscopic examination and by the loss of membrane asymmetry (as indicated by phosphatidylserine externalization) and the fragmentation of nuclear DNA into distinct subunits. Cells in the early stages of apoptosis demonstrated a reduced susceptibility to adherence by a number of strains of C. albicans. A correlation between the decrease in yeast adherence and the loss of membrane asymmetry, associated with the early stages of apoptosis, was established.

Annexin A5↗

Two-deoxyglucose as an anti-metabolite in human carcinoma cell line RPMI-2650 and drug-resistant variants.

The accumulation of 2-deoxyglucose (2-DG), a glycolytic inhibitor, was investigated in a human nasal carcinoma cell line, RPMI-2650 and two of its drug-resistant variants (selected with taxol and melphalan) to assess manipulation of glycolytic potential as a selective means of reducing resistance. 2-DG uptake was increased 3-fold and 9.9-fold in taxol- and melphalan-resistant variants of RPMI-2650, respectively. Two of the principal factors associated with increased 2-DG uptake, namely glucose transporters and hexokinase activity, were increased in the resistant variants. Other changes in glucose metabolism that may affect 2-DG as an antimetabolite were observed, including increases in glucose-6-phosphate dehydrogenase of 10-fold and 100-fold for taxol- and melphalan-resistant variants, respectively, suggesting higher pentose phosphate activity; increased glutamine utilisation and greater sensitivity to iodoacetic acid-induced depletion of ATP levels in the parent relative to the resistant variants.

Antimetabolites, Antineoplastic↗

Expression and prognostic relevance of Mcl-1 in breast cancer.

BACKGROUND: Bcl-2, an anti-apoptotic protein, is frequently associated with favourable prognosis in breast cancer. The potential role of mcl-1, another bcl-2 family member, in breast cancer has not yet been defined. PATIENTS AND METHODS: This study examined the expression of mcl-1 and bcl-2 in 170 cases of invasive primary breast carcinoma, using reverse-transcriptase polymerase chain reaction and immunohistochemical analyses. RESULTS: Expression of bcl-2 mRNA and protein were found to be favourably associated with outcome for patients, supporting a prognostic role for bcl-2 in breast cancer, whereas mcl-1 expression, at the mRNA or protein level, did not correlate with tumour size, grade, lymph node or ER status, age of patient at diagnosis, or disease outcome. CONCLUSION: As these analyses of mcl-1 expression may have co-detected mcl-1(S/deltaTM) (a more recently identified, shorter variant, that may be pro-apoptotic) with the anti-apoptotic wild-type of mcl-1, it is possible that future studies may indicate some significant clinical correlations if the isoforms can be independently investigated.

Adult↗