PubMed Health⌕ Search

Biomedical subjects

M Bibby

Publications and source records attributed to M Bibby.

5 recordsLinked to original sources
PubMed2004

Anticancer drug response and expression of molecular markers in early-passage xenotransplanted colon carcinomas.

Despite some success in the treatment of colorectal carcinomas, novel rational therapies targeting specific cancer-related molecules are under development and urgently needed. These approaches need careful preclinical evaluation in models that closely mirror the clinical situation. Therefore, we established a panel of 15 xenotransplantable tumours directly from fresh surgical material. We showed that both the histology and expression of tumour-associated markers (Epithelial Cell Adhesion molecule (EpCAM), E-cadherin, carcinoembryonic antigen (CEA)) could be maintained during passaging in nude mice. Xenotransplanted tumours were characterised for chemosensitivity and revealed a response rate of 5/15 (33%) for 5-fluorouracil (5-FU), 15/15 (100%) for irinotecan and 8/14 (57%) for oxaliplatin. 5 patients out of 15 were treated with cytostatics because of synchronous metastases. The response to chemotherapy in these patients coincided very closely with the response of the individual xenografts. All of the xenografts expressed the proliferation marker Ki67 and the nuclear enzyme, Topoisomerase IIalpha (Topo IIalpha) at the protein level. Most of the xenografts also expressed the tumour suppressor, p53 (9/14) and the nuclear enzyme Topoisomerase Ialpha (Topo Ialpha) (13/14) at the protein level. Interestingly, the presence of a K-ras mutation in codon 12 (5/15 xenografts) coincided with a low response rate towards oxaliplatin. This observation needs further confirmation using a larger number of tumours. In conclusion, we were able to establish transplantable xenografts suitable to mimic the clinical situation. These well characterised models are useful tools for the preclinical development of novel therapeutic approaches and for investigating translational research aspects.

Animals↗
PubMed2004

Quantitative angiogenesis assays in vivo--a review.

The development of agents that target tumour vasculature is ultimately dependent on the availability of appropriate preclinical screening assays. Several quantitative angiogenesis assays exist, each with its own unique characteristics and disadvantages. In this review we discuss some of the commonly used assays, their methodological pitfalls and current use. The corneal micropocket and the CAM assay are well established. However, the matrix-implant assays have the potential advantage of replicating the hypoxic tumour microenvironment, thus making them suitable for the study of tumour angiogenesis. The ideal quantitative angiogenesis assay does not exist and the use of two complimentary quantitative assays, such as a matrix implant assay and a microcirculatory preparation like the CAM or corneal micropocket assay, provides the best compromise. Newer models like the hollow-fibre assay are being developed and older ones refined. Assay systems should reflect distinct disease processes. Thus it is appropriate to develop assays that study exclusively pro- or anti-angiogenic compounds or anti-vascular agents. Criticisms of currently available screening systems are that the predictive value of current screening systems remains to be established as anti-angiogenic agents are still in clinical development. Anti-angiogenic agents are likely to be most effective as chronic therapy for remission maintenance in the metastatic setting or as adjuvant therapy in patients at high risk of relapse, an important clinical aspect not addressed in animal models of tumour angiogenesis. Histological analysis still provides the most detailed information on in vivo angiogenesis. However, angiogenesis is a dynamic process and assays that permit continuous monitoring of the angiogenic response and provide information on the physiological characteristics of new vessels will be distinctly advantageous over older systems. The development of non-invasive techniques for quantitation of angiogenesis will greatly facilitate this process.

Animals↗
PubMed2000

The delivery of antisense therapeutics.

Antisense oligonucleotides, ribozymes and DNAzymes have emerged as novel, highly selective inhibitors or modulators of gene expression. Indeed, their use in the treatment of diseases arising from genetic abnormalities has become a real possibility over the past few years. The first antisense drug molecule is now available for clinical use in Europe and USA. However, their successful application in the clinic will require improvements in cellular targeting and intracellular delivery. This review aims to look at recent advances in the in vitro and in vivo delivery of antisense oligodeoxynucleotides and ribozymes.

Animals↗
PubMed1999

Chemokines induce the cellular migration of MCF-7 human breast carcinoma cells: subpopulations of tumour cells display positive and negative chemotaxis and differential in vivo growth potentials.

We previously reported that chemotactic cytokines (chemokines) induce the directional migration of cells derived from the breast carcinoma cell line MCF-7 in vitro, however it was apparent that only a small percentage of cells displayed the ability to migrate upon stimulation. In the present study three sub-lines derived from the parental MCF-7 cell line were selected for their ability to migrate in response to MIP-1alpha, MIP-1beta or RANTES across Transwell filters of 8 microm pore size. The first round selection of migratory cells resulted in sub-populations which demonstrated an increased chemotactic response compared with parental cells. Cells migrating to MIP-1beta were subjected to four further rounds of positive or negative selection, resulting in two sub-lines, MCF-7L4 and MCF-7U4 which displayed an increased and decreased chemotactic response respectively to MIP-1alpha MIP-1beta and RANTES. No difference in chemokine receptor RNA message expression between these sub-lines and the parental MCF-7 line were detected, although increased levels of alpha3, alpha6 and alphav integrin sub-units were shown for MCF-7L4 (positively selected sub-line) compared with MCF-7U4 cells. Moreover, the in vivo growth of cells derived from the two MCF-7 sub-lines was inversely correlated with their chemotactic response. The results of this study depict further the inherent heterogeneity in cancer, suggesting that the chemotactic response may influence the migratory traits of sub-populations within the tumour and potentially contribute to their in vivo behavior, growth and survival.

Breast Neoplasms↗