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Michael J Bradley

Publications and source records attributed to Michael J Bradley.

6 recordsLinked to original sources
PubMed2006

Met-Independent Hepatocyte Growth Factor-mediated regulation of cell adhesion in human prostate cancer cells.

BACKGROUND: Prostate cancer cells communicate reciprocally with the stromal cells surrounding them, inside the prostate, and after metastasis, within the bone. Each tissue secretes factors for interpretation by the other. One stromally-derived factor, Hepatocyte Growth Factor (HGF), was found twenty years ago to regulate invasion and growth of carcinoma cells. Working with the LNCaP prostate cancer progression model, we found that these cells could respond to HGF stimulation, even in the absence of Met, the only known HGF receptor. The new HGF binding partner we find on the cell surface may help to clarify conflicts in the past literature about Met expression and HGF response in cancer cells. METHODS: We searched for Met or any HGF binding partner on the cells of the PC3 and LNCaP prostate cancer cell models, using HGF immobilized on agarose beads. By using mass spectrometry analyses and sequencing we have identified nucleolin protein as a novel HGF binding partner. Antibodies against nucleolin (or HGF) were able to ameliorate the stimulatory effects of HGF on met-negative prostate cancer cells. Western blots, RT-PCR, and immunohistochemistry were used to assess nucleolin levels during prostate cancer progression in both LNCaP and PC3 models. RESULTS: We have identified HGF as a major signaling component of prostate stromal-conditioned media (SCM) and have implicated the protein nucleolin in HGF signal reception by the LNCaP model prostate cancer cells. Antibodies that silence either HGF (in SCM) or nucleolin (on the cell surfaces) eliminate the adhesion-stimulatory effects of the SCM. Likewise, addition of purified HGF to control media mimics the action of SCM. C4-2, an LNCaP lineage-derived, androgen-independent human prostate cancer cell line, responds to HGF in a concentration-dependent manner by increasing its adhesion and reducing its migration on laminin substratum. These HGF effects are not due to shifts in the expression levels of laminin-binding integrins, nor can they be linked to expression of the known HGF receptor Met, as neither LNCaP nor clonally-derived C4-2 sub-line contain any detectable Met protein. Even in the absence of Met, small GTPases are activated, linking HGF stimulation to membrane protrusion and integrin activation. Membrane-localized nucelolin levels increase during cancer progression, as modeled by both the PC3 and LNCaP prostate cancer progression cell lines. CONCLUSION: We propose that cell surface localized nucleolin protein may function in these cells as a novel HGF receptor. Membrane localized nucleolin binds heparin-bound growth factors (including HGF) and appears upregulated during prostate cancer progression. Antibodies against nucleolin are able to ameliorate the stimulatory effects of HGF on met-negative prostate cancer cells. HGF-nucleolin interactions could be partially responsible for the complexity of HGF responses and met expression reported in the literature.

Cell Adhesion↗
PubMed2006

A survey about phacoemulsification incision thermal contraction incidence and causal relationships.

PURPOSE: To ascertain the rate and related factors of phacoemulsification wound burns. DESIGN: Survey. METHODS: We conducted a survey of 523 ophthalmologists in Utah, Colorado, Montana, South Dakota, and Oregon. RESULTS: One hundred six doctors (20.3%) responded and provided data on 76,581 procedures and 75 wound burns (0.98/1000 procedures). Twenty-one wounds (28%) occurred during early sculpting, and 53 wounds (71%) occurred during fragment removal. Wound burns were found to be associated with surgical approach (P = .003), phacoemulsification unit (P = .007), and unit settings (P < .001). CONCLUSION: Wound burns continue to be a serious complication; however, advances in technology and surgical technique help.

Body Temperature↗
PubMed2006

Analysis of an approach to astigmatism correction during cataract surgery.

PURPOSE: To determine if a system of astigmatic keratomy at the time of cataract surgery is safe and effective. SETTING: Academic Ophthalmology Center. METHODS: One hundred and ten consecutive patients with greater than 0.50 diopters (d) of cylinder with the rule (WTR) and 0.75 d against the rule (ATR) were enrolled. Those with an axis between 16 and 74 degrees and 106 and 164 degrees were defined as oblique axis. Peripheral clear corneal relaxing incisions 600 mum deep were used with a nomogram of 60 degrees length per 1.0 d of attempted correction. Keratometry was taken from IOL Master biometry and refractive results at 4-12 weeks were compared. RESULTS: 60.5% of ATR, 62% of WTR and 23% of oblique attempted correction was achieved. Splitting the patients to under and over 70 years of age had no impact on the results. Of the 14 overcorrected, 7 had oblique cylinder (p = 0.009) and 10 had less than 1 d of preoperative cylinder (p = 0.00015). CONCLUSIONS: Using the IOL Master topography with this nomogram was quite effective in reducing preoperative cylinder. Oblique axis results were unpredictable, however, and much more likely to lead to an overcorrection.

Aged↗
PubMed2004

Cellular interactions in the tropism of prostate cancer to bone.

At autopsy >or=80% of prostate cancers have established macrometastases in marrow containing bone. The mechanism(s) to explain this remarkable level of bone involvement remain to be elucidated. We examined the adhesive and invasive behavior of prostate cancer cells to osteoblastic and human bone marrow endothelial cells (HBME-1) in an attempt to explain the tropism of prostate cells for bone. We found an inverse relationship between adhesion and prostate cell tumorigenicity and metastatic potential. Relative cell adhesion of P69 between cell lines was 1.74-fold (95% confidence interval [CI] = 1.15-2.64) and 1.58-fold (95% CI = 0.94-2.68) greater at 1 hr and 2 hr, respectively, than LNCaP that was essentially equivalent to C4-2 cells when using an osteoblastic cell line, D1 as the substrate. Similar results were acquired when HBME-1 were used as substratum. There was a marked increase in adhesion of the poorly tumorigenic cell line P69 as compared to the cancer cells to HBME-1. P69 adhesion was 2.78-fold (95% CI = 1.87-4.84) and 2.0-fold (95% CI = 1.43-2.80) greater at 1 hr and 2 hr, respectively when compared to LNCaP or C4-2 cells. D1 cells, a bone homing osteoblastic precursor, behaved contrary to the metastatic, bone-colonizing C4-2 cell line and bound best to other bone cells but not as well as a non-homing fetal bone marrow-derived cell line, D2. Invasion of prostate cancer cells through HBME-1 lawns was examined at 8 hr and 16 hr. In contrast to the adhesion studies, the invasion of the more aggressive C4-2 cells was 3.46-fold (95% CI = 1.18-10.17) and 2.65-fold (95% CI = 1.26-5.56) greater at 8 hr and 16 hr, respectively than LNCaP cells. Similarly, LNCaP cell invasion was 1.73-fold (95% CI = 0.69-4.37) and 2.35-fold (95% CI = 1.41-3.93) greater at 8 hr and 16 hr, respectively than P69 cells at the invasion of HBME-1 monolayers. At 8 hr, C4-2 cells had 6.0-fold (95% CI = 2.63,13.65) higher invasive potential than P69 cells. Phage display biopanning of LNCaP cells versus C4-2 cells in vitro using 4 separate techniques repeatedly identified the same peptide in support of minimal cell surface changes associated with the ability of C4-2 cells to metastasize to bone. As integrins are vital to cell adhesion and migration, we examined the integrin subunit expression in the prostate cell lines. The expression of integrin subunits is much higher in the nontumorigenic cell line, P69, whereas the differences in integrin expression between LNCaP and C4-2 are negligible. Only alpha(2) and beta(5) integrin subunits increase from LNCaP to C4-2. Given that C4-2 cells spontaneously metastasize to bone in vivo and LNCaP cells do not, these studies imply that the ability of a metastatic prostate cancer cell to colonize the bone is not completely dependent upon the ability of the cancer cell to adhere to either osteoblastic cells or to the bone marrow endothelial cell lining. Therefore, the initial interaction between the bone endothelium or stroma and prostate cells is not accurately referred to as a tropic or homing response. The invasion assay results indicate that the invasive potential of the cell more accurately reflects the bone colonizing potential of a prostate cancer cell. It is likely that bidirectional paracrine interactions, subsequent to marrow adhesion, between prostate cancer cells and the bone microenvironment are what determine the successful colonization of the bone by prostate cancer cells. Further, functional changes in surface proteins that are involved in invasion are likely to occur without major changes in levels of cell surface protein expression. Functional integrin association, substratum usage and outside in signaling are more likely to predict metastatic behavior.

Bone Marrow Cells↗
PubMed2002

Reducing global NOx emissions: developing advanced energy and transportation technologies.

Globally, energy demand is projected to continue to increase well into the future. As a result, global NOx emissions are projected to continue on an upward trend for the foreseeable future as developing countries increase their standards of living. While the US has experienced improvements in reducing NOx emissions from stationary and mobile sources to reduce ozone, further progress is needed to reduce the health and ecosystem impacts associated with NOx emissions. In other parts of the world, (in developing countries in particular) NOx emissions have been increasing steadily with the growth in demand for electricity and transportation. Advancements in energy and transportation technologies may help avoid this increase in emissions if appropriate policies are implemented. This paper evaluates commercially available power generation and transportation technologies that produce fewer NOx emissions than conventional technologies, and advanced technologies that are on the 10-year commercialization horizon. Various policy approaches will be evaluated which can be implemented on the regional, national and international levels to promote these advanced technologies and ultimately reduce NOx emissions. The concept of the technology leap is offered as a possibility for the developing world to avoid the projected increases in NOx emissions.

Air Pollution↗