120 research outputs found
Biomechanical and molecular aspects of pulmonary vascular disease in children with congenital heart disease
Biomechanical and molecular aspects of pulmonary vascular disease in children with congenital heart disease
Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model
AbstractSmall cell lung cancer (SCLC) is a highly aggressive human tumor with a more than 95% mortality rate. Its ontogeny and molecular pathogenesis remains poorly understood. We established a mouse model for neuroendocrine (NE) lung tumors by conditional inactivation of Rb1 and Trp53 in mouse lung epithelial cells. Mice carrying conditional alleles for both Rb1 and Trp53 developed with high incidence aggressive lung tumors with striking morphologic and immunophenotypic similarities to SCLC. Most of these tumors, which we designate MSCLC (murine small cell lung carcinoma), diffusely spread through the lung and gave rise to extrapulmonary metastases. In our model, inactivation of both Rb1 and p53 was a prerequisite for the pathogenesis of SCLC
Changes in epidermal radiosensitivity with time associated with increased colony numbers
Epidermal clonogenic cell survival and colony formation following
irradiation were investigated and related to radiosensitivity. A rapid in
vivo/in vitro assay was developed for the quantification of colonies
arising from surviving clonogenic cells in pig epidermis after
irradiation. Bromodeoxyuridine (BrdU)-labelled cells in full thickness
epidermal sheets were visualized using standard immunohistochemistry. In
unirradiated skin, approximately 900 BrdU-positive cells mm(-2) were
counted. In a time sequence experiment, BrdU-positive cell numbers
increased from an average of 900 cells mm(-2) to approximately 1400 cells
mm(-2) after BrdU-labelling for 2-24 h. In irradiated skin, colonies
containing >/=16 BrdU-positive cells were seen for the first time at days
14/15 after irradiation. The number of these colonies per cm(2) as a
function of skin surface dose yielded a cell survival curve with a
D(0)-value (+/-SE) of 3.9+/-0.6 Gy. This relatively high D(0)-value is
possibly due to a rapid fall off in depth dose distribution for the
iridium-192 source and consequently a substantial contribution of hair
follicular epithelium to colony formation. At 14/15 days after
irradiation, the ED(50) level of 33.6 Gy for the in vivo response of moist
desquamation corresponded with 2.7 colonies cm(-2). Surprisingly, the
number of colonies increased with time after irradiation with an estimated
doubling time of approximately 4 days, while the D(0)-value remained
virtually unchanged. This increase in colony numbers could be due to
migration of clonogenic cells, to the recruitment of dormant clonogenic
cell survivors by elevated levels of cytokines, or to both. Although
frequent biopsying caused increased cytokine levels, which had a systemic
effect on unirradiated skin, it had no influence on colony formation in
irradiated skin. Smaller colonies, containing 4-8 cells or 9-15 cells,
were abundant, particularly after higher doses, which resulted in higher
D(0)-values. The majority of these small colonies were abortive and did
not progress to larger colonies. There was no statistical evidence for
significant variations in the interanimal responses
Primary Leiomyosarcoma of the Adrenal Gland
We report a rare case of a primary leiomyosarcoma of the adrenal gland. A 73-year-old woman presented with an inferior
vena cava syndrome. MR imaging was suggestive of a large tumour originating from the right adrenal gland. Angiography
revealed a tumour vascularised by the right adrenal artery. At explorative laparotomy a tumour of 27 cm in diameter was
found which was completely fixed to the liver; the tumour was therefore considered unresectable. As a consequence of the
mechanical problems caused by this large tumour, the patient died 3 weeks after the operation. Autopsy revealed no distant
metastases or other primary tumour site
Frequent germ-line succinate dehydrogenase subunit D gene mutations in patients with apparently sporadic parasympathetic paraganglioma
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