ABSTRACT
Vascular endothelial growth factor (VEGF), a major factor mediating tumor stromal angiogenesis, is expressed as five splice variants encoded by a single gene (VEGF121, VEGF145, VEGF165, VEGF189 and VEGF206). Recently, we demonstrated that the cell-associated isoform, VEGF189, plays important roles in establishment of human colon and esophageal cancer xenografts. We have established 228 xenografts originating from various human solid tumors. In this study, we investigated the expression patterns of VEGF isoforms in those tumor xenografts by RT-PCR. The isoform patterns were VEGF121/VEGF165 in 27 xenografts (11.8%) and VEGF121/VEGF165/VEGF189 in 201 (88.2%). All human solid tumor xenografts expressed VEGF189 more frequently than primary tumors reported previously. These results suggest that VEGF189 contributes to the successful xenotransplantability of various human solid tumors via augmentation of stromal vascularization.
Subject(s)
Endothelial Growth Factors/biosynthesis , Lymphokines/biosynthesis , Neoplasms, Experimental/metabolism , Neoplasms, Experimental/pathology , Neoplasms/metabolism , Neoplasms/pathology , Animals , Endothelial Growth Factors/genetics , Humans , Lymphokines/genetics , Mice , Mice, Nude , Mice, SCID , Neoplasm Transplantation , Neoplasms, Experimental/blood supply , Neovascularization, Pathologic , Protein Isoforms/biosynthesis , Protein Isoforms/genetics , RNA Splicing , Transplantation, Heterologous , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth FactorsABSTRACT
A 32-year-old man of Irish descent presented with severe progressive headache and sensorineural hearing loss. MRI/magnetic resonance angiography head scans were normal. A length-dependent sensorimotor peripheral neuropathy with autonomic dysfunction predated these symptoms. Systemic organ involvement and transthyretin (TTR) amyloid immunostaining of bone marrow and fat aspirate were documented. Direct DNA sequencing revealed both the normal TTT (phenylalanine) and a new variant TCT (serine) at position 44 of the TTR gene. This case expands the genotypic and phenotypic variability within TTR amyloidosis.
Subject(s)
Amyloidosis/genetics , Hearing Loss, Sensorineural/genetics , Peripheral Nervous System Diseases/genetics , Point Mutation , Polymorphism, Single-Stranded Conformational , Prealbumin/genetics , Serine , Adult , Amino Acid Sequence , Amyloidosis/pathology , Amyloidosis/physiopathology , Base Sequence , Exons , Headache , Hearing Loss, Sensorineural/pathology , Hearing Loss, Sensorineural/physiopathology , Humans , Ireland/ethnology , Magnetic Resonance Angiography , Magnetic Resonance Imaging , Male , Peripheral Nervous System Diseases/pathology , Peripheral Nervous System Diseases/physiopathology , Polymerase Chain Reaction , Prealbumin/chemistry , United StatesABSTRACT
Effect of peribronchial lung parenchyma on bronchial collapsibility during the maximum expiration was studied in the dog lung. Maximum expiratory flow volume curve (MEFVC) was obtained from dogs with intact parenchyma (I), parenchyma being dissected away from main lobar bronchi 1.5 cm in depth (II) and the dissected parenchyma glued to the bronchi with adhesive substance (III). Lung elastic pressure-volume curve and airway resistance were almost unchanged in the three conditions. Maximum expiratory flow (V max) in condition II was considerably decreased and the ratio of decrease to the control value was high at the lower lung volumes. V max in condition III was significantly higher than the control values except at the very low lung volumes. It was proved that even if the airway down to segmental bronchi was dessected from peribronchial lung parenchyma, V max was significantly limited. It was concluded that the radial traction of peribronchial parenchyma to the bronchi reduced bronchial collapsibility considerably, and in the dissected bronchi of condition II dynamic airway collapse would occur very easily.
