Cell Kinetic, Molecular and Clinical Analysis of Growth Factor Sensitization of Myeloid Leukemia1

2015 ◽  
pp. 112-136
Author(s):  
Michael Andreeff ◽  
Johannes Drach ◽  
Shourong Zhao ◽  
Ugo Consoli ◽  
Susan Escudier ◽  
...  
Keyword(s):  
Growth Factor ◽  
Clinical Analysis ◽  
Cell Kinetic

Molecular and Clinical Analysis of Locally Advanced Dermatofibrosarcoma Protuberans Treated With Imatinib: Imatinib Target Exploration Consortium Study B2225

2005 ◽  
Vol 23 (4) ◽  
pp. 866-873 ◽  
Author(s):  
Grant A. McArthur ◽  
George D. Demetri ◽  
Allan van Oosterom ◽  
Michael C. Heinrich ◽  
Maria Debiec-Rychter ◽  
...  
Keyword(s):  
Growth Factor ◽  
Clinical Response ◽  
Metastatic Disease ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Dermatofibrosarcoma Protuberans ◽  
Clinical Analysis ◽  
Platelet Derived Growth Factor ◽  
Clinical Activity ◽  
Clinical Responses

Purpose The cutaneous malignant tumor dermatofibrosarcoma protuberans (DFSP) is typically associated with a translocation between chromosomes 17 and 22 that places the platelet-derived growth factor–B (PDGFB) under the control of the collagen 1A1 promoter. The purpose of this study was to evaluate molecular, cytogenetic, and kinase activation profiles in a series of DFSPs and to determine whether these biologic parameters are correlated with the clinical responses of DFSP to imatinib. Patients and Methods We analyzed the objective radiologic and clinical response to imatinib at 400 mg twice daily in eight patients with locally advanced DFSP and two patients with metastatic disease. Results Each of eight patients with locally advanced DFSP had evidence of t(17;22) and showed a clinical response to imatinib. Four of these patients had complete clinical responses. The two patients with metastatic disease had fibrosarcomatous histology and karyotypes that were substantially more complex than those typically associated with localized DFSP. One patient with metastatic DFSP and an associated t(17;22) had a partial response to imatinib but experienced disease progression after 7 months of therapy. In contrast, the other patient with metastatic disease had a tumor lacking t(17;22), and there was no clinical response to imatinib. Unexpectedly, there was minimal platelet-derived growth factor receptor–beta phosphorylation in the untreated DFSP, despite the documented presence of a PDGFB autocrine mechanism. Conclusion Imatinib has clinical activity against both localized and metastatic DFSP with t(17;22). However, fibrosarcomatous variants of DFSP lacking t(17;22) may not respond to imatinib.

scholarly journals Cell kinetic studies in the murine ventral tongue epithelium: the effects of repeated exposure to keratinocyte growth factor

2002 ◽  
Vol 35 ◽  
pp. 22-31 ◽  
Author(s):  
C. S. Potten ◽  
D. Booth ◽  
N. J. Cragg ◽  
J. A. O'Shea ◽  
G. L. Tudor ◽  
...  
Keyword(s):  
Growth Factor ◽  
Keratinocyte Growth Factor ◽  
Kinetic Studies ◽  
Repeated Exposure ◽  
Cell Kinetic ◽  
Tongue Epithelium

Quantitative Microscopic Comparison of the Organization of the Lung in Transgenic Mice Expressing Transforming Growth Factor-α (TGF-α)

1996 ◽  
Vol 54 ◽  
pp. 14-15
Author(s):  
C. G. Plopper ◽  
C. Helton ◽  
A. J. Weir ◽  
J. A. Whitsett ◽  
T. R. Korfhagen
Keyword(s):  
Growth Factor ◽  
Pulmonary Fibrosis ◽  
Transgenic Mice ◽  
Blood Vessels ◽  
Lung Parenchyma ◽  
Lung Maturation ◽  
Alveolar Air ◽  
Parenchymal Tissue ◽  
Air Space ◽  
Conducting Airways

A wide variety of growth factors are thought to be involved in the regulation of pre- and postnatal lung maturation, including factors which bind to the epidermal growth factor receptor. Marked pulmonary fibrosis and enlarged alveolar air spaces have been observed in lungs of transgenic mice expressing human TGF-α under control of the 3.7 KB human SP-C promoter. To test whether TGF-α alters lung morphogenesis and cellular differentiation, we examined morphometrically the lungs of adult (6-10 months) mice derived from line 28, which expresses the highest level of human TGF-α transcripts among transgenic lines. Total volume of lungs (LV) fixed by airway infusion at standard pressure was similar in transgenics and aged-matched non-transgenic mice (Fig. 1). Intrapulmonary bronchi and bronchioles made up a smaller percentage of LV in transgenics than in non-transgenics (Fig. 2). Pulmonary arteries and pulmonary veins were a smaller percentage of LV in transgenic mice than in non-transgenics (Fig. 3). Lung parenchyma (lung tissue free of large vessels and conducting airways) occupied a larger percentage of LV in transgenics than in non-transgenics (Fig. 4). The number of generations of branching in conducting airways was significantly reduced in transgenics as compared to non-transgenic mice. Alveolar air space size, as measured by mean linear intercept, was almost twice as large in transgenic mice as in non-transgenics, especially when different zones within the lung were compared (Fig. 5). Alveolar air space occupied a larger percentage of the lung parenchyma in transgenic mice than in non-transgenic mice (Fig. 6). Collagen abundance was estimated in histological sections as picro-Sirius red positive material by previously-published methods. In intrapulmonary conducting airways, collagen was 4.8% of the wall in transgenics and 4.5% of the wall in non-transgenic mice. Since airways represented a smaller percentage of the lung in transgenics, the volume of interstitial collagen associated with airway wall was significantly less. In intrapulmonary blood vessels, collagen was 8.9% of the wall in transgenics and 0.7% of the wall in non-transgenics. Since blood vessels were a smaller percentage of the lungs in transgenics, the volume of collagen associated with the walls of blood vessels was five times greater. In the lung parenchyma, collagen was 51.5% of the tissue volume in transgenics and 21.2% in non-transgenics. Since parenchyma was a larger percentage of lung volume in transgenics, but the parenchymal tissue was a smaller percent of the volume, the volume of collagen associated with parenchymal tissue was only slightly greater. We conclude that overexpression of TGF-α during lung maturation alters many aspects of lung development, including branching morphogenesis of the airways and vessels and alveolarization in the parenchyma. Further, the increases in visible collagen previously associated with pulmonary fibrosis due to the overexpression of TGF-α are a result of actual increases in amounts of collagen and in a redistribution of collagen within compartments which results from morphogenetic changes. These morphogenetic changes vary by lung compartment. Supported by HL20748, ES06700 and the Cystic Fibrosis Foundation.

A role for the actin cytoskeleton in the hormonal and growth-factor-mediated activation of protein kinase B

2001 ◽  
Vol 353 (3) ◽  
pp. 735
Author(s):  
K. PEYROLLIER ◽  
E. HAJDUCH ◽  
A. GRAY ◽  
G. J. LITHERLAND ◽  
A. R. PRESCOTT ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Actin Cytoskeleton ◽  
Protein Kinase B
Sign in / Sign up

Export Citation Format

Share Document