Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 5 de 5
Filter
Add more filters










Database
Language
Publication year range
1.
Ann Oncol ; 24(12): 2994-8, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24114856

ABSTRACT

BACKGROUND: Some studies investigating the prognostic value of lymph vascular space invasion (LVSI) have shown an association between LVSI and disease-free survival. Definitive criteria and optimal determination of this parameter remain unclear, however, especially regarding the clinical relevance of LVSI quantification. PATIENTS AND METHODS: A subset of node-negative breast carcinomas from premenopausal patients from the European Organization for the Research and Treatment of Cancer trial 10854 (assessing efficacy of perioperative chemotherapy patients with T1-T3, N0-2, and M0 breast cancer (BC) was selected and scored for LVSI. In 358 evaluable breast carcinomas, the number of LVSI foci and tumor cells was determined in the largest tumor embolus within the lymph vessels. These two parameters were multiplied to calculate the LVSI tumor burden (LVSI TB). The optimal cutoff for this parameter was calculated in a test set (N = 120), tested in a validation set (N = 238), and compared with simple quantitation of the number of LVSI foci. RESULTS: Tumors with a single LVSI focus are not associated with increased risk for relapse [hazard ratio (HR) 1.423, 95% confidence interval (CI) 0.762-2.656]. The LVSI TB had higher sensitivity and specificity compared with simple determination of the number of LVSI foci. LVSI TB was independently associated with disease-free survival in the validation set (HR 2.366, 95% CI 1.369-4.090, P = 0.002) in multivariate analysis and provided prognostic information in both the low- and high-risk node-negative BC groups (P < 0.001 and P = 0.007, respectively). CONCLUSION: The determination of the number of LVSI foci multiplied by the number of tumor cells gives the most reliable quantitative assessment of this parameter, which can provide prognostic information in node-negative BC.


Subject(s)
Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Lymphatic Vessels/pathology , Adult , Breast Neoplasms/therapy , Carcinoma, Ductal, Breast/therapy , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Neoplasm Invasiveness , Prognosis , Proportional Hazards Models , Risk , Treatment Outcome , Young Adult
2.
J Biol Chem ; 273(48): 32038-41, 1998 Nov 27.
Article in English | MEDLINE | ID: mdl-9822677

ABSTRACT

Hepatic lipase (HL) and scavenger receptor type B class I (SR-BI) have both been implicated in high density lipoprotein (HDL)-cholesteryl ester uptake in cholesterol-utilizing tissues. Inactivation of HL by gene-directed targeting in mice results in up-regulation of SR-BI expression in adrenal gland (Wang, N., Weng, W., Breslow, J. L., and Tall, A. R. (1996) J. Biol. Chem. 271, 21001-21004). The net effect on HDL-cholesteryl ester uptake is not known. We determined the impact of acute in vivo inhibition of rat adrenal HL activity by antibodies on SR-BI expression and on human and rat HDL-[3H]cholesteryl ether (CEth) uptake in the adrenal gland. Rat HDL was isolated from rats in which HL activity had been inhibited for 1 h. The rats were studied under basal conditions (not ACTH-treated) and after previous treatment with ACTH for 6 days (ACTH-treated). Intravenous injection of anti-HL resulted in 70% lowering of adrenal HL activity in both conditions which were maintained for at least 8 h. In not ACTH-treated rats, inhibition of adrenal HL increased adrenal SR-BI mRNA (5.2-fold) and mass (1. 6-fold) within 4 h. HL inhibition resulted in 41% and 14% more adrenal accumulation of human HDL-[3H]CEth during 4 and 24 h, respectively. The adrenal uptake of rat HDL-[3H]CEth increased by 68%, 4 h after the antibody injection. ACTH treatment increased total adrenal HL activity from 3.7 +/- 0.5 milliunits to 34.0 +/- 17. 2 milliunits, as well as adrenal SR-BI mRNA from 2.9 +/- 0.7 arbitrary units (A.U.) to 86.8 +/- 41.1 A.U. and SR-BI mass from 7.7 +/- 1.8 A.U. to 63.16 +/- 46.7 A.U. The human HDL-[3H]CEth uptake by adrenals was also significantly increased from 0.58 +/- 0.11% of injected dose to 7.24 +/- 1.58% of injected dose. Inhibition of adrenal HL activity did not result in further induction of SR-BI expression and did not affect human HDL-[3H]CEth uptake. These findings indicate that SR-BI expression may be influenced by changes in HL activity. HL activity is not needed for the SR-BI-mediated HDL-cholesteryl ester uptake by rat adrenal glands.


Subject(s)
Adrenal Glands/metabolism , CD36 Antigens/biosynthesis , CD36 Antigens/genetics , Cholesterol, HDL/metabolism , Ethers/metabolism , Lipoprotein Lipase/antagonists & inhibitors , Membrane Proteins , Receptors, Immunologic , Adrenal Glands/drug effects , Adrenocorticotropic Hormone/pharmacology , Animals , Biological Transport , DNA Primers , Humans , Kinetics , Male , Mice , Polymerase Chain Reaction , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Rats , Rats, Wistar , Receptors, Lipoprotein/biosynthesis , Receptors, Lipoprotein/genetics , Receptors, Scavenger , Scavenger Receptors, Class B , Time Factors , Transcription, Genetic , Up-Regulation
3.
Mol Cell Endocrinol ; 126(1): 35-40, 1997 Jan 03.
Article in English | MEDLINE | ID: mdl-9027361

ABSTRACT

Hepatic lipase (HL) gene expression was studied in rat ovaries. A transcript lacking exons 1 and 2 could be detected by reverse transcription-polymerase chain reaction (RT-PCR) in the ovaries of mature cyclic females and of immature rats treated with pregnant mare serum followed by human chorionic gonadotropin (hCG) to induce superovulation. By competitive RT-PCR the HL transcript was quantified. Low levels of HL mRNA were detected in ovaries of mature cyclic females and of immature rats. During superovulation HL mRNA was several fold higher than in mature cyclic rats and transiently increased to a maximum at 2 days after hCG treatment. Pulse-labelling of ovarian cells and ovarian slices with [35S]methionine followed by immunoprecipitation with polyclonal anti-HL IgGs showed de novo synthesis of a 47 kDa HL-related protein. Expression of the protein was transiently induced by gonadotropins with a peak at 2 days after hCG treatment. Induction of liver-type lipase activity occurred only after HL mRNA and synthesis of the HL-related protein had returned to pre-stimulatory levels. We conclude that in rat ovaries the HL gene is expressed into a variant mRNA and a 47 kDa protein. The expression of the HL gene in ovaries is inducible and precedes the expression of the mature, enzymatically active liver-type lipase.


Subject(s)
Gene Expression/drug effects , Gonadotropins/pharmacology , Lipase/genetics , Liver/enzymology , Ovary/metabolism , Animals , Chorionic Gonadotropin/pharmacology , Female , Gonadotropins, Equine/pharmacology , Lipase/biosynthesis , Ovary/drug effects , Ovulation Induction , Polymerase Chain Reaction , RNA, Messenger/analysis , RNA-Directed DNA Polymerase , Rats , Rats, Wistar , Superovulation
4.
Biochem J ; 318 ( Pt 2): 463-7, 1996 Sep 01.
Article in English | MEDLINE | ID: mdl-8809034

ABSTRACT

Lipoprotein lipase (LPL) is functionally active only as a dimer. It is also generally assumed that the highly homologous hepatic lipase functions as a dimer, but no clear evidence has been presented. A hepatic lipase-like activity, also indicated as L-type lipase, is present in adrenal and ovary tissues. This enzyme is thought to originate from the liver and to be identical to hepatic lipase. We determined the functional molecular mass of hepatic lipase in rat liver, adrenal gland and ovary by radiation inactivation, a method for determining the functional size of a protein without the need of prior purification. Samples were exposed to ionizing radiation at -135 degrees C. Hepatic lipase activity in liver homogenate showed a single exponential decay. The functional molecular mass was calculated to be 63 +/- 10 kDa. Hepatic lipase activity in adrenal homogenate was found to have a functional molecular mass of 117 +/- 16 kDa. The functional molecular masses of the lipases partially purified from rat liver perfusate, adrenal homogenate or ovarian homogenate showed the same pattern, a target mass for the liver enzyme of 56 +/- 6 kDa and a target mass of 117 +/- 14 kDa for the enzyme from adrenal gland or ovary. In Western blot analysis the mass of the structural units of hepatic lipase in liver was 57 kDa and in adrenal and ovary tissue 51 kDa. We conclude that the functional unit of hepatic lipase in the liver is a monomer. The enzyme in adrenal gland and ovary is different from the liver and the functional unit may be a dimer.


Subject(s)
Adrenal Glands/enzymology , Lipase/chemistry , Liver/enzymology , Ovary/enzymology , Animals , Blotting, Western , Dose-Response Relationship, Radiation , Electrophoresis, Polyacrylamide Gel , Female , Kinetics , Lipase/antagonists & inhibitors , Lipase/radiation effects , Male , Molecular Weight , Organ Specificity , Rats , Rats, Wistar
5.
Trop Doct ; 22(2): 91, 1992 Apr.
Article in English | MEDLINE | ID: mdl-1604735
SELECTION OF CITATIONS
SEARCH DETAIL
...