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Biomedical subjects

J B Mitchell

Publications and source records attributed to J B Mitchell.

At least 19 recordsLinked to original sources
PubMed2006

Transcriptional responses to ionizing radiation reveal that p53R2 protects against radiation-induced mutagenesis in human lymphoblastoid cells.

The p53 protein has been implicated in multiple cellular responses related to DNA damage. Alterations in any of these cellular responses could be related to increased genomic instability. Our previous study has shown that mutations in p53 lead to hypermutability to ionizing radiation. To investigate further how p53 is involved in regulating mutational processes, we used 8K cDNA microarrays to compare the patterns of gene expression among three closely related human cell lines with different p53 status including TK6 (wild-type p53), NH32 (p53-null), and WTK1 (mutant p53). Total RNA samples were collected at 1, 3, 6, 9, and 24 h after 10 Gy gamma-irradiation. Template-based clustering analysis of the gene expression over the time course showed that 464 genes are either up or downregulated by at least twofold following radiation treatment. In addition, cluster analyses of gene expression profiles among these three cell lines revealed distinct patterns. In TK6, 165 genes were upregulated, while 36 genes were downregulated. In contrast, in WTK1 75 genes were upregulated and 12 genes were downregulated. In NH32, only 54 genes were upregulated. Furthermore, we found several genes associated with DNA repair namely p53R2, DDB2, XPC, PCNA, BTG2, and MSH2 that were highly induced in TK6 compared to WTK1 and NH32. p53R2, which is regulated by the tumor suppressor p53, is a small subunit of ribonucleotide reductase. To determine whether it is involved in radiation-induced mutagenesis, p53R2 protein was inhibited by siRNA in TK6 cells and followed by 2 Gy radiation. The background mutation frequencies at the TK locus of siRNA-transfected TK6 cells were about three times higher than those seen in TK6 cells. The mutation frequencies of siRNA-transfected TK6 cells after 2 Gy radiation were significantly higher than the irradiated TK6 cells without p53R2 knock down. These results indicate that p53R2 was induced by p53 protein and is involved in protecting against radiation-induced mutagenesis.

Cells, Cultured↗
PubMed2006

Relationship between locking-bolt torque and load pre-tension in the Ilizarov frame.

The wire-bolt interface in an Ilizarov frame has been mechanically tested. The optimal torque to be applied to the frame locking-bolts during physiological loading has been defined. The set-up configuration was as is used clinically except a copper tube was used to simulate bone. The force-displacement curves of the Ilizarov wires are not altered by locking-bolt torque. The force in the bone model at which pre-tension is lost increases as the locking-bolts are tightened to 14 Nm torque, but decreases if torque exceeds 14 Nm. Thus, 14 Nm is the optimal locking-bolt torque in frame. The relationship between pre-tension versus load for different locking-bolt torques arises because at low and high clamping torques poor wire holding and plastic deformation respectively occur. Wire damage was seen under light and electron microscopy. Clinically, over or under-tightening locking-bolts will cause loss of pre-tension, reduction in frame stiffness and excessive movement at the fracture site, which may be associated with delayed union.

Biomechanical Phenomena↗
PubMed2004

Tailored sinc pulses for uniform excitation and artifact-free radio frequency time-domain EPR imaging.

A method to generate shaped radiofrequency pulses for uniform excitation of electron spins in time-domain radio frequency (RF) electron paramagnetic resonance (EPR) imaging is presented. A commercial waveform generator was integrated with the transmit arm of the existing time-domain RF-EPR spectrometer to generate tailored excitation pulses with sub-nano second resolution for excitation with a 90 degrees flip-angle. A truncated sinc [sin(x)/x] pulse, tailored to compensate for the Q-profile (RF frequency response) of the resonator, was shown to yield images from phantom objects as well as in vivo images, with minimal distortion. These studies point to the advantages in using shaped sinc pulses to achieve improved uniform excitation over a relatively wide bandwidth region in time-domain RF-EPR imaging (RF-FT-EPRI).

Animals↗
PubMed2003

The effect of pre-exercise cooling on high intensity running performance in the heat.

The purpose of this study was to determine the effect of pre-exercise cooling on high intensity, moderate duration running performance and thermoregulatory responses in a hot environment (38 degrees C, 40 %RH). On separate days, 11 male subjects completed two treadmill runs to exhaustion at 100% of maximal aerobic power with (CL) and without (CT) pre-exercise cooling. Cooling consisted of 20 min of standing rest in a 22 degrees C environment with fan cooling (4.0 m x sec -1) and water spraying (50 ml x min -1) applied to both anterior and posterior body surfaces. Core temperature (T(c)) was determined with an esophageal T(es) probe, and skin temperatures (T(sk)) were measured using surface thermistors positioned at four sites. Finger prick blood samples were taken before and after exercise for the determination of blood lactate. Heart rates and ratings of thermal sensations and comfort were also recorded. Time to exhaustion was significantly shorter in the CL condition (368.9 +/- 56.2) compared to the CT condition (398.8 +/- 55.5 sec). Peak T(es) (37.51 +/- 0.57 vs. 38.56 +/- 0.30 degrees C for CL and CT, respectively), T(sk) (34.18 +/- 1.22 vs. 36.15 +/- 0.70 degrees C for CL and CT, respectively), rates of heat gain (0.20 +/- 0.05 vs. 0.28 +/- 0.05 degrees C x min -1 for CL and CT, respectively), and net heat storage (238.4 +/- 109.6 vs. 531.9 +/- 78.3 kJ for CL and CT, respectively) were all lower in the CL compared to CT throughout the treadmill runs. There were no differences in lactate accumulation between the two conditions. Based on these data, it can be concluded that pre-exercise cooling influences thermoregulatory responses during high intensity, moderate duration exercise; however, performance is impaired compared to a control trial in which no cooling procedures were employed.

Adult↗
PubMed2002

Feasibility and assessment of non-invasive in vivo redox status using electron paramagnetic resonance imaging.

PURPOSE: To test the feasibility of electron paramagnetic resonance imaging (EPRI) to provide non-invasive images of tissue redox status using redox-sensitive paramagnetic contrast agents. MATERIAL AND METHODS: Nitroxide free radicals were used as paramagnetic agents and a custom-built 300 MHz EPR spectrometer/imager was used for all studies. A phantom was constructed consisting of four tubes containing equal concentrations of a nitroxide. Varying concentrations of hypoxanthine/xanthine oxidase were added to each tube and reduction of the nitroxide was monitored by EPR as a function of time. Tumor-bearing mice were intravenously infused with a nitroxide and the corresponding reduction rate was monitored on a pixel-by-pixel basis using 2D EPR of the tumor-bearing leg and normal leg serving as control. For animal studies, nitroxides were injected intravenously (1.25 mmol/kg) and EPR projections were collected every 3 min after injection using a magnetic field gradient of 2.5 G/cm. The reduction rates of signal intensity on a pixel-by-pixel basis were calculated and plotted as a redox map. Redox maps were also collected from the mice treated with diethylmaleate (DEM), which depletes tissue thiols and alters the global redox status. RESULTS: Redox maps obtained from the phantoms were in agreement with the intensity change in each of the tubes where the signals were decreasing as a function of the enzymatic activity, validating the ability of EPRI to accurately access changes in nitroxide reduction. Redox imaging capability of EPR was next evaluated in vivo. EPR images of the nitroxide distribution and reduction rates in tumor-bearing leg of mice exhibited more heterogeneity than in the normal tissue. Reduction rates were found to be significantly decreased in tumors of mice treated with DEM, consistent with the depletion of thiols and the consequent alteration of the redox status. CONCLUSION: Using redox-sensitive paramagnetic contrast agents, EPRI can non-invasively discriminate redox status differences between normal tissue and tumors.

Animals↗
PubMed2001

Cellular sites of H2O2-induced damage and their protection by nitroxides.

While the exact mechanism of H2O2-induced cytotoxicity is unknown, there is considerable evidence implicating DNA as a primary target. A recent study showed that a cell-impermeable nitroxide protected mammalian cells from H2O2-induced cell killing and suggested that the protection was mediated through cell membrane-bound or extracellular factors. To further define the protective properties of nitroxides, Chinese hamster V79 cells were exposed to H2O2 with or without cell-permeable and impermeable nitroxides and selected metal chelators. EPR spectroscopy and paramagnetic line broadening agents were used to distinguish between intra- and extracellular nitroxide distribution. To study the effectiveness of nitroxide protection, in the absence of a cell membrane, H2O2-mediated damage to supercoiled plasmid DNA was evaluated. Both deferrioxamine and Tempol cross the cell membrane, and inhibited H2O2-mediated cell killing, whereas the cell-impermeable DTPA and nitroxide, CAT-1, failed to protect. Similar protective effects of the chelators and nitroxides were observed when L-histidine, which enhances intracellular injury, was added to H2O2. In contrast, when damage to plasmid DNA was induced (in the absence of a cell membrane), both nitroxides were protective. Collectively, these results do not support a role for membrane-bound or extracellular factors in mediating H2O2 cytotoxicity in mammalian cells.

Animals↗
PubMed2001

Comparison of control of Listeria by nitric oxide redox chemistry from murine macrophages and NO donors: insights into listeriocidal activity of oxidative and nitrosative stress.

The physiological function of nitric oxide (NO) in the defense against pathogens is multifaceted. The exact chemistry by which NO combats intracellular pathogens such as Listeria monocytogenes is yet unresolved. We examined the effects of NO exposure, either delivered by NO donors or generated in situ within ANA-1 murine macrophages, on L. monocytogenes growth. Production of NO by the two NONOate compounds PAPA/NO (NH2(C3H6)(N[N(O)NO]C3H7) and DEA/NO (Na(C2H5)2N[N(O)NO]) resulted in L. monocytogenes cytostasis with minimal cytotoxicity. Reactive oxygen species generated from xanthine oxidase/hypoxanthine were neither bactericidal nor cytostatic and did not alter the action of NO. L. monocytogenes growth was also suppressed upon internalization into ANA-1 murine macrophages primed with interferon-gamma (INF-gamma) + tumor necrosis factor-alpha (TNF-alpha or INF-gamma + lipid polysaccharide (LPS). Growth suppression correlated with nitrite formation and nitrosation of 2,3-diaminonaphthalene elicited by stimulated murine macrophages. This nitrosative chemistry was not dependent upon nor mediated by interaction with reactive oxygen species (ROS), but resulted solely from NO and intermediates related to nitrosative stress. The role of nitrosation in controlling L. monocytogenes was further examined by monitoring the effects of exposure to NO on an important virulence factor, Listeriolysin O, which was inhibited under nitrosative conditions. These results suggest that nitrosative stress mediated by macrophages is an important component of the immunological arsenal in controlling L. monocytogenes infections.

2-Naphthylamine↗
PubMed2001

Concurrent paclitaxel and radiation in the treatment of locally advanced head and neck cancer.

PURPOSE: To determine the feasibility of an organ preservation regimen consisting of infusional paclitaxel administered concurrently with radiotherapy to patients with locally advanced head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Thirty-three previously untreated patients with stage III or IV tumors were enrolled onto the study. Paclitaxel was administered as a 120-hour continuous infusion every 3 weeks during the course of radiation therapy. Sixteen patients received a paclitaxel dose of 105 mg/m(2), and 17 patients received 120 mg/m(2). Radiation was delivered in a standard format at 1.8 Gy/d to a total dose of 70.2 to 72 Gy. RESULTS: Three months after therapy, a 76% complete response (CR) at the primary site and a 70% overall CR was achieved. At 36 months, locoregional control was 55.7%, overall survival was 57.8%, and disease-free survival was 51.1%. The median survival duration for all 33 patients was greater than 50 months at the time of this report. Local toxicities including mucositis, dysphagia, and skin reactions were severe but tolerable. All patients retained functional speech, and all but four patients were swallowing food 3 months after treatment. Steady-state plasma concentrations for paclitaxel were not achieved during a 120-hour infusion, suggesting a nonlinear process. Tumor volume quantified by pretreatment computerized tomography imaging was associated with likelihood of response and survival. CONCLUSION: Paclitaxel administered as a 120-hour continuous infusion in combination with radiotherapy is a feasible and promising treatment for patients with advanced HNSCC.

Adult↗
PubMed2001

Multifunctional antioxidant activity of HBED iron chelator.

The use of N,N'-bis (2-hydroxybenzyl) ethylenediamine-N,N'-diacetic acid (HBED) for iron chelation therapy is currently being tested. Besides its affinity for iron, bioavailability, and efficacy in relieving iron overload, it is important to assess its anti- and/or pro-oxidant activity. To address these questions, the antioxidant/pro-oxidant effects of HBED in a cell-free solution and on cultured Chinese hamster V79 cells were studied using UV-VIS spectrophotometry, oximetry, spin trapping, and electron paramagnetic resonance (EPR) spectrometry. The results indicate that HBED facilitates Fe(II) oxidation but blocks O2(.-)-induced reduction of Fe(III) and consequently pre-empts production of .OH or hypervalent iron through the Haber-Weiss reaction cycle. The efficacy of HBED as a 1-electron donor (H-donation) was demonstrated by reduction of the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate)-derived nitrogen-centered radical cation (ABTS(.+)), accompanied by formation of a short-lived phenoxyl radical. HBED also provided cytoprotection against toxicity of H2O2 and t-BuOOH. Our results show that HBED can act both as a H-donating antioxidant and as an effective chelator lacking pro-oxidant capacity, thus substantiating its promising use in iron chelation therapy.

Animals↗
PubMed2001

Magnetic resonance imaging for in vivo assessment of tissue oxygen concentration.

Magnetic resonance imaging (MRI) provides high-resolution morphological images useful in diagnostic radiology to differentiate normal from abnormal/pathological states. More recently, emerging developments in MRI seek to add a functional/physiological dimension to the anatomic images to provide better understanding of the physiology of pathological conditions. Three MRI methods offer the promise of providing important physiologic information, such as oxygen status and redox capability of tissues, and these are discussed in the context of their potential usefulness to radiation oncology. The techniques include blood oxygen level-dependent (BOLD) MRI, Overhauser enhanced MRI (OMRI), and electron paramagnetic resonance imaging (EPRI). BOLD MRI provides information of tumor oxygen status by using the differences in MRI images from tumors obtained when breathing air or carbogen. Deoxyhemoglobin serves as an endogenous BOLD MRI contrast agent. OMRI utilizes the enhancement of proton MRI images by a nontoxic free radical contrast agent. The advantages of this technique are the very low magnetic fields used and its capability to provide quantitative information of tissue oxygen concentration. EPRI also uses free radical contrast agents and can provide redox and oxygen status differences between tumor and normal tissues. Some of the contrast agents used in EPRI have been identified as radiation protectors. The images obtained from each of the technologies may ultimately be used to overlay their respective views (containing spatial tissue physiology information) onto detailed anatomic maps.

Humans↗
PubMed2001

Electron paramagnetic resonance for small animal imaging applications.

Magnetic resonance imaging (MRI) provides high-resolution morphological images useful in diagnostic radiology to differentiate between normal and abnormal/pathological states in tissues. More recently, emerging developments in MRI have added a functional/physiological dimension to anatomical images. Electron paramagnetic resonance (EPR), a magnetic resonance technique similar to nuclear magnetic resonance, detects paramagnetic species such as free radicals. Like MRI, EPR can be implemented as an imaging technique for small animals and potentially human applications. Because of the low abundance of naturally occurring paramagnetic species, exogenous paramagnetic species are needed for in vivo EPR imaging (EPRI). The image data from EPRI contain both spatial distribution of paramagnetic species and spectral information. Hence, spatially encoded functional information such as tissue oxygen status and redox status can be extracted and coregistered with the spatial distribution of the spin probe, to the anatomy, or both by suitable means. Ultimately, the images obtained from EPRI may be used to overlay the functional information (containing spatial tissue physiology information) onto detailed anatomical maps. With its ability to enable whole animal imaging in mice, EPRI will be a useful imaging technique that complements other techniques such as MRI and positron emission tomography in obtaining valuable functional/physiological images.

Anatomy, Cross-Sectional↗
PubMed2001

Adaptation to eccentric exercise: neutrophils and E-selectin during early recovery.

The purpose was to determine the responses of blood neutrophils and E-selectin concentrations during early recovery (<24hr) from 2 bouts of eccentric exercise. Subjects (N=9) completed 2 bouts of eccentric arm exercise using their non-dominant arm (Bout 1 and Bout 2) and 1 non-exercise control condition. The exercise bouts were separated by 4 weeks, and the control condition preceded bout 1. Neutrophil concentrations were significantly higher at 3, 6, and 9-hr post-exercise for Bout 1 relative to Bout 2 and control. No significant changes in blood E-selectin concentrations were observed. Isometric strength deficit was similar for Bout 1 and Bout 2 at 5 min and 3 hr post exercise and was significantly great for Bout 1 relative to Bout 2 at 6, 9, and 24-hr post-exercise. The adaptation to eccentric exercise is associated with a lower concentration of blood neutrophils during early recovery. The neutrophilia associated with novel eccentric arm exercise precedes secondary changes in isometric strength and is not associated with changes in the concentration of blood E-selectin.

Adaptation, Physiological↗
PubMed2001

Is Smad3 a major player in signal transduction pathways leading to fibrogenesis?

Transforming growth factor (TGF)-beta plays a central role in fibrosis, contributing both to the influx and activation of inflammatory cells, as well as to activation of fibroblasts to elaborate extracellular matrix. In the past few years, new insight has been gained into signal transduction pathways downstream of the TGF-beta receptor serine-threonine kinases with the identification of a family of evolutionarily conserved Smad proteins. Two receptor-activated Smad proteins, Smad2 and Smad3, are phosphorylated by the activated TGF-beta type I receptor kinase, after which they partner with the common mediator, Smad4, and are translocated to the nucleus to where they participate in transcriptional complexes to control expression of target genes. We have shown in wound healing studies of mice null for Smad3, that loss of this key signaling intermediate interferes with the chemotaxis of inflammatory cells to TGF-beta as well as with their ability to autoinduce TGF-beta. Moreover, studies with mouse embryo fibroblasts null for Smad3 show that TGF-beta-dependent induction of c-Jun and c-Fos, important in induction of collagen as well as in autoinduction of TGF-beta, is mediated by Smad3. Based on these observations, we hypothesize that loss of Smad3 will confer resistance to fibrosis and result in reduced inflammatory cell infiltrates, reduced autoinduction of TGF-beta, important to sustain the process, and reduced elaboration of collagen. Preliminary observations in a model of radiation-induced fibrosis confirm this hypothesis and suggest that inhibitors of Smad3 might have clinical application both to improve wound healing and to reduce fibrosis.

DNA-Binding Proteins↗
PubMed2001

Impact of the Oregon Health Plan on children with special health care needs.

OBJECTIVE: Although an increasing number of Medicaid children are enrolled in Medicaid managed care plans, little is known about how children with special health care needs fare under such programs. Of particular concern is the ability of such children to navigate a managed care system and gain access to specialty and other services. This study compares the managed care experiences of children with and without special care needs in the Oregon Health Plan. METHODOLOGY: Telephone surveys were conducted with a sample of parents of children enrolled in the Oregon Health Plan. Three groups of children were sampled: Supplemental Security Income (SSI) children with disabilities, children with asthma, and children without special health care needs. Descriptive and multivariate analyses were conducted to determine the impact of Medicaid managed care on access and satisfaction. RESULTS: Children with disabilities in managed care plans did not experience any more difficulty accessing needed specialty care than did those without special health care needs. Children with asthma, however, reported higher levels of unmet need. There were no differences in access between children with disabilities enrolled in managed care and those children with disabilities remaining in fee-for-service. CONCLUSIONS: Unlike SSI children with disabilities, children who were not SSI-eligible but had asthma seemed to have difficulty obtaining some services. These children were not eligible for the same consumer protections afforded SSI children by Oregon. If states want to enroll all children with special health care needs into managed care programs, they must develop mechanisms for identifying such children and ensuring that they receive medically necessary services.

Asthma↗
PubMed2001

The influence of different external cooling methods on thermoregulatory responses before and after intense intermittent exercise in the heat.

The purpose of this study was to determine the effect of different cooling methods on thermoregulation before and after intermittent anaerobic exercise in the heat (38 degrees C). On separate days, 10 men completed 4 conditions consisting of 2 sets of six 30-second sprints (with 30 seconds of rest) at 125% of maximal aerobic power with each set of sprints followed by a cooling procedure. The 4 conditions were the following: passive cooling at room temperature (22 degrees C; PRC), fan cooling (4.0 m x s(-1), 22 degrees C; FAC), fan cooling with water spraying (50 ml x min(-1); FWC), and a noncooling passive recovery in the heat chamber (38 degrees C; PCC). Each set of 6 sprints was followed by a 12-minute cooling period; after the second 12-minute period, cooling continued until esophageal temperature (Tes) was reduced by 1.0 degrees C. Tes and mean skin temperatures (Tsk) were taken before and during exercise and during all cooling phases. Cooling rates (mean +/- SEM) after the second set of sprints (based on Tes) were greater (p < 0.05) in PRC (0.043 +/- 0.007) than in the other conditions (FWC = 0.027 degrees +/- 0.005 degrees, FAC = 0.03 degrees +/- 0.004 degrees, and PCC = 0.021 degrees +/- 0.003 degrees C per minute). Overall decreases in heat content, however, were greater in the FWC (-332.2 +/- 27.8) and FAC (-129.9 +/- 14.7 kJ) conditions compared with the PRC condition (29.0 +/- 14.9 kJ). The time required to lower Tes by 1.0 degrees C with PRC (22.8 +/- 1.8) was less than with FAC (30.4 +/- 2.7 minutes). Finally, the rate of increase in Tes during the second set of sprints was less in the FAC and FWC conditions (0.15 degrees +/- 0.01 degrees and 0.11 degrees +/- 0.01 degrees C per minute) compared with the PCC and PRC conditions (0.19 degrees +/- 0.01 degrees and 0.18 degrees +/- 0.01 degrees C per minute), suggesting differences in pre-exercise cooling. Based on cooling rates and the time required to lower Tes by 1.0 degrees C, PRC was the most effective method of cooling. The conclusion is different, however, when taking into account changes in heat content since the FAC and FWC conditions were more effective in dissipating heat and in preventing heat gain during the second set of sprints

Adult↗
PubMed2000

S-nitrosoglutathione reduces nonocclusive thrombosis rate following balloon overstretch injury and intracoronary irradiation of porcine coronary arteries.

PURPOSE: Intracoronary radiation (IR) suppresses neointima formation following balloon injury in animal models. High doses of radiation exacerbate thrombosis and delay re-endothelialization. The free radical nitric oxide (NO) has been reported to inhibit platelet aggregation, reduce neointimal hyperplasia, and stimulate re-endothelialization. This study examined the effects of a chemical NO donor on neointima formation, thrombosis, and healing of irradiated porcine coronary arteries. METHODS AND MATERIALS: Vascular lesions were created in the coronary arteries of 59 domestic swine by overstretch balloon injury. Arteries were then left untreated or were treated with intracoronary gamma-radiation using Iridium-192 in each artery to deliver 5 or 15 Gy at 2 mm from the center of the source. The chemical NO donor S-nitrosoglutathione (GSNO) was infused i.v. at a rate of 250 microg/min for 10 min before injury, followed by a continuous infusion for 60 min. Animals were euthanized at 14 days and their arteries were analyzed for histomorphometric indices of proliferation and thrombosis. RESULTS: A dose of 15 Gy reduced the ratio of intimal area to medial fracture length (IA/FL) versus control (0.06 +/- 0.05 0.54 +/- 0.10 [p < 0. 001]) but increased the nonocclusive thrombosis rate compared to controls (85% vs. 30%; p < 0.05). A low dose of 5 Gy did not affect neointima formation. Treatment with GSNO reduced thrombosis in all treated groups: control, 15%; 5 Gy, 18%; and 15 Gy, 35% (p < 0.05) without affecting neointima formation. CONCLUSION: Systemic administration of GSNO during balloon injury and IR was tolerated well by the swine and resulted in reduction of the thrombosis rate, especially at high doses, without apparent effect on neointima formation.

Animals↗
PubMed2000

Radiation and the Apo2L/TRAIL apoptotic pathway preferentially inhibit the colonization of premalignant human breast cells overexpressing cyclin D1.

The role of cyclin D1 overexpression in human breast premalignancy was investigated using immortal, nontumorigenic MCF-10A cells. Previous work documented that cyclin D1 overexpression promoted in vitro anchorage-independent colonization. We now report that the colonization of MCF-10A cyclin D1 transfectants was preferentially inhibited by gamma-radiation and specific classes of apoptosis inducers [Apo-2 ligand (Apo-2L), but not tumor necrosis factor alpha]. Antibody inhibition studies and semiquantitative PCR indicated that radiation inhibition of colonization was partially mediated via the Apo2L/TRAIL pathway. The apoptotic removal of cyclin D1-overexpressing, colonization-competent premalignant breast cells by Apo2L/TRAIL or other biologicals may represent a novel approach to the prevention of breast cancer.

Apoptosis↗