Tumor Angiogenesis and the Role of Paracrine Mediators: Molecular Basis of Oncology

Chapter: Tumor Angiogenesis and the Role of Paracrine Mediators Summary: Designed for the non-scientist, this volume, Molecular Basis of Oncology, explores the exciting new applications of molecular biology to cancer care. Especially important are the ability to make an early diagnosis using genetic markers and the knowledge of tumor biology giving hope for cure. The most exciting changes have been in prostate, colon, lung and breast cancer, and leukemia which are all covered here in an accessible format for the clinician with all the complex terminology and techniques explained and the findings put into clinical perspective. The book crosses interface between molecular biology and clinical medicine; explores new screening, diagnosis, and treatment possibilities; and begins with an overview for non-experts then progresses to specific clinical diseases where molecular biology has been of use in diagnosis and management

Basic fibroblast growth factor and fibroblast growth factor receptor I are implicated in the growth of human astrocytomas.

Malignant astrocytomas are highly invasive, vascular neoplasms that comprise the majority of nervous system tumors in humans. A strong association has previously been made between malignancy in human astrocytic tumors and increased expression of certain fibroblast growth factor (FGF) family members, including basic and acidic FGF. The influence of endogenous basic FGF on glioblastoma cell growth in vitro was evaluated using basic FGF-specific antisense oligonucleotides. These studies indicated that human glioblastoma cell growth in vitro, can be inhibited by suppressing basic FGF expression. Human astrocytomas also exhibited changes in FGF receptor (FGFR) expression during the course of their progression from a benign to a malignant phenotype. FGFR2 (bek) expression was abundant in normal white matter and in all low grade astrocytomas, but was not observed in glioblastomas. Conversely, FGFR1 (flg) expression was absent or barely detectable in normal white matter, but was significantly elevated in glioblastomas. Glioblastomas also expressed an alternatively spliced form of FGFR1 containing two immunoglobulin-like disulfide loops (FGFR1 beta), whereas normal human adult and fetal brain expressed a form of the receptor containing three immunoglobulin-like disulfide loops (FGFR1 alpha). Intermediate grades of astrocytic tumors exhibited a gradual loss of FGFR2 and a shift in expression from FGFR1 alpha to FGFR1 beta as they progressed from a benign to a malignant phenotype. The underlying cytogenetic changes that contribute to these alterations are not entirely understood, but abnormalities in the p53 tumor suppressor gene may influence expression of bFGF as well as the FGFR. These results suggest that alterations in FGFR signal transduction pathways may play a critical role in the malignant progression of astrocytic tumors

Conjugated desferoxamine attenuates hepatic microvascular injury following ischemia/reperfusion.

Iron-dependent oxy radicals have been implicated in reperfusion injury. Although the iron chelator desferoxamine (DFO) is beneficial, its hemodynamic effects and short vascular retention limit its use in vivo. We tested whether DFO conjugated to a high-molecular-weight starch might ameliorate in vivo hepatic microvascular injury without adverse side effects following 120 min of ischemia. Prior to reperfusion, conjugated DFO (100 mg/kg), vehicle (Veh), or saline (I/R) was administered. After 90 min of reperfusion, blood was collected for serum transaminase determination (ALT; U/liter), and fluorescein-albumin was injected to label perfused microvessels, which were quantified in frozen sections by a point-count technique. Tissue edema was estimated by wet to dry weight ratios (W/D). Reperfusion results in hepatocyte injury (rise in ALT and W/D) and a 30% loss of perfused microvessels. Intravenous administration of conjugated DFO produces no significant change in systemic hemodynamics, whereas both ALT and tissue edema were decreased by approximately 50%. Moreover, perfused microvessels were restored virtually to nonischemic control levels. Enhanced perfusion and attenuated cell injury with DFO suggest that microvascular failure and resultant cell death are mediated, at least in part, by iron-dependent mechanisms in reperfusion

Susceptibility of Hepatic Microcirculation to Reperfusion Injury: A Comparison of Adult and Suckling Rats.

Primary graft failure and vascular thromboses are frequent complications of liver transplantation, yet the mechanisms responsible remain unclear. Previous work from our laboratory has shown that hepatic reperfusion injury results in damage at the microvessel level. The present study was performed to determine whether an increased susceptibility of immature animals to microvascular injury during reperfusion might be a contributing factor in these complications. Suckling (35 to 50 g) or adult (250 to 400 g) rats were subjected to 30 or 60 minutes of hepatic ischemia to the left and median lobes followed by 90 minutes of reperfusion. Control animals were sham-operated, time-matched rats. At the end of reperfusion, fluorescein-labeled albumin was injected systemically to mark perfused sinusoids. Frozen sections of liver biopsies were viewed under fluorescence microscopy. The perfused sinusoid density was determined by point count analysis and expressed as the number of intersections of perfused sinusoids with 25 randomly oriented points superimposed on the sinusoid field. In sham-operated rats, at both 30 and 60 minutes, there were no differences between sucklings and adults. After 30 minutes of ischemia and 90 minutes of reperfusion, adults showed a significantly decreased density of perfused sinusoids (4.5 +/- 0.1 intersections per field) when compared with suckling rats (6.0 +/- 0.3 intersections per field, P less than .001). However, in rats subjected to 60 minutes of ischemia followed by 90 minutes of reperfusion, the microvascular injury was more severe in suckling rats (2.7 +/- 0.2 intersections per field) than in adults (4.7 +/- 0.2 intersections per field, P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS

Park Views May-June 1960

Park Views May-June 1960 Topics: Practical Nurses Begin Training Radio is Gift of Lions Club Pediatrics Dept. Nurses Benefited Employees\u27 Picnic Service Awards Given Attendance Records White Cross News Comic on the Hospital Visitor (Smoke Screen Schmoe) Photographs with names: Cover: Philip Wasson First Class of Practical Nursing Students: Mrs. Janet Fritz, Mrs. Helen Alexander, Miss Ester Brueck, Mrs. Elizabeth Bennett, Mrs. Mallie Craig, Mrs. Barbara Fruechtenicht, Mrs. Verna Smith, Miss Eva Brooks, Mrs. Betty Funck Lions Club: Tony Competti, Herman Armstrong, Mrs. Margot Kayer, Stanley R. Nelson Pediatrics: Mrs. Florence Schafer, Miss Marie Kolter, Pediatrics: Mrs. Edmund Sembroski, Mrs. Tom Goulaff, Patrica Schindeldecker, Mrs. Howard Dennis Employee Picnic Cluster: David Perry, Don Wasson, Lana Baker, Lucille Morris Awards: Harold McMillen, Jennie Welshimer Awards: Stanley R. Nelson, Irene McConnell, Bob McConnell Council Officers: Mrs. Val Waggoner, Mrs. Dean Trainer, Mrs. W.O. Hughs, Mrs. Ralph Westrick, Mrs. Ralph Doctor, Mrs. Harry Cole, Mrs. Nelson McClurg, Mrs. Harry Magner, Mrs. Kenneth Richards, Mrs. Henry Reidenbach, Mrs. Gerald Botteron, Mrs. A. Paul Striaght White Cross: Bob Robinson, Ruth Cook, Mary Heymannhttps://researchrepository.parkviewhealth.org/archives/1001/thumbnail.jp

Park Views March-April 1960

Park Views Mar-Apr 1960 Topics: Surgical Hostess Service Begins Students Seek Lamp Sponsors Board of Directors Hospital Are People... Comic on the Hospital Visitor Photographs with names: Surgical Hostesses: Mrs. Mahlon Miller, Mrs. Basil Overton, Mrs. David Rolland Lamp staff members: Barbara Bowman, Dorothy Crow, Carol Fetters, Sharon Zawadske, Janet Cox, Kay Ancil, Kay Flegal, Dorothy Bowman, Judy Shindeldecker, Alice Drage, Joan Beaudway, Karon Holman, Mary Kay Hall, Beverly Stevens, Phyllis Trick Board of Directors: Harold McMillen, Harold MacKinnon, Harold Bobeck, Louis Wade, Clyde Cover, Rev. Gerald Jones, Sol Rothberg, Ermin Ruf, Allen Sheldon, Rev. Byron Stroh, Herbert Cooper, Rev. Bryant Howard Director of Nutrition: Lois Gumpper, Kay Stephanoff Isolette: Mrs. Walter Shady, Mrs. Harry Magner, Mrs. Adena Carneyhttps://researchrepository.parkviewhealth.org/archives/1000/thumbnail.jp