Biomedical subjects

P Bonomi

Publications and source records attributed to P Bonomi.

95 records · Page 6Linked to original sources

PubMedDate not supplied

An interaction between type 1 and type 2 programmed cell death and clonogenic survival.

UNLABELLED: We suggest two additional reasons why current, non-surgical therapies for most solid, epithelial-derived cancers can lack effectiveness. Studies with panc-1 human pancreatic cancer cells cultured with actinomycin D and/or MK 886 indicate firstly, that type 2 (intrinsic, autophagic, mitochondrial-dependent, MK 886-induced) programmed cell death is less effective than the type 1 (apoptotic, extrinsic, ligand-dependent, actinomycin D-induced) form in reducing the number of residual clonogenic cells, and secondly, that activation of cellular suicide during their combined culture results in a greater number of residual clonogenic cells compared with either agent alone. HYPOTHESIS: Based on results from the culture of panc-1 cells with MK 886 and/or actinomycin D, we suggest that in this system, and possibly in others: (a) type 2 programmed cell death is a less effective inhibitor of residual cells with clonogenic potential, and (b) activation together of both forms of PCD increases the number of residual clonogenic cells.

Antibiotics, Antineoplastic↗

PubMedDate not supplied

Altered oncogene, tumor suppressor and cell-cycle gene expression in PANC-1 cells cultured with the pleiotrophic 5-lipoxygenase inhibitor, MK886, assessed with a gene chip.

We describe a genomic response of mRNAs associated with a subset of oncogenes, tumor suppressor and cell cycle-related genes in proliferating human Panc-1 pancreatic cancer cells after 24 hours of culture with MK886, a pleotrophic 5-lipoxygenase inhibitor. Ninety-eight of these cDNAs are represented in one of the sub-arrays included in the Clontech Human cDNA Expression Array. In this initial analysis, control cells exhibited apparent widespread low levels of disparate mRNA synthesis. In cells cultured with 40 microM MK886 for 24 hr, while most expressed genes, including a number of specific proliferation-enhancing genes such as c-myc were inhibited, 19 other ones including some countervailing genes including tyrosine SRC protein kinase, cyclins B1 and D1, CDC25B phosphatase and 40s ribosomal S19, amounting to 19 percent of the cDNAs resident on the chip were up-regulated at > 1.10 experimental/control values. Therapy-induced activation of compensatory proliferative genomic responses provides an additional explanation why malignant cells can fail therapy. Among their many future uses, gene chips clearly will be an extremely powerful tool for identifying relationships between the hierarchical linear and non-linear control and implementation-related cellular events and for identifying potential molecular targets tor cancer therapy.

Blotting, Western↗

PubMedDate not supplied

[Antileukocyte antibodies. Synthetic review and experimental data].

An account is given about the results of investigations carried out in repeatedly transfused patients. We observed an increased presence of the antileucocyte antibodies in relation to the repeatedly transfused patients. The work was extended also to the repeatedly pregnancies; in this research it was also observed a sensibly increased presence of the antileucocyte antibodies in relation with the number of the pregnancies.

Agglutination Tests↗

PubMedDate not supplied

[Laboratory tests applied to transfusion problems. Identification of dangerous universal donors and their frequency].

We studied 504 subjects, whose blood group wes O; they were periodic or occasional blood donors from Transfusional Center A.V.I.S., Policlinico "Umberto I", Roma. Our research was based on the principle stated by Gandini: he states that the natural isoagglutinin concentration equal or superior to 1:200 and the presence of hemolytic isoantibodies may make universal donors dangerous. Our results indicated that the percentage of this kind of donors is 27.75%. Sice 17.26% of our studied subjects showed hemolytic antibodies, we consider it is sufficient to identify dangerous donors through a dosage of hemolytic isoantibodies.

Blood Donors↗

PubMedDate not supplied

An in vivo inhibitor of 5-lipoxygenase, MK886, at micromolar concentration induces apoptosis in U937 and CML cells.

MK886 (Merck Frosst) is a selective in vivo inhibitor of 5-lipoxygenase, active at nanomolar concentrations. At micromolar concentrations, it inhibited the proliferation of U937 monoblastoid cells and of cultured malignant cells from patients with chronic myelogenous leukemia. These cells became morphologically apoptotic, a form of physiologic cell death. U937 cell apoptosis was assessed by flow cytometry, ultrastructure, DNA laddering and immuno-histology for free 3'OH-DNA. MK886-induced apoptosis developed over time as cells were recruited in concert with reduction in their numbers. Some CML cells exhibited cytoplasmic changes of apoptosis without typical nuclear changes. Under conditions used for measuring Ca2+ with Fura 2, 10 micromolar MK886 increased U937 intracellular Ca2+ 4-fold or more over the 8 minute period of measurement. Since MK886 inhibits the association of arachidonic acid with the 5-lipoxygenase activating protein, altered arachidonic acid metabolism may have contributed to these results.

Apoptosis↗