Abstract Oophorectomy in a woman’s early adult years substantially lowers her risk of breast cancer.1–4 This is an example of the abundant epidemiological and endocrine data which indicate that estrogens are involved in sporadic breast cancer and promote growth.5–8 Oophorectomy also reduces the risk of breast cancer among BRCA1 mutation carriers,9 which hints at the general role of estrogens in the proliferation of breast epithelial cells. Due to the striking effect of ovariectomy, it is assumed that the majority of breast cancers originate as estrogen-dependent lesions and later progress gradually to a hormone-independent state. Since 1896,10 estrogen-deprivation treatment has been used for the treatment of breast cancer. On average, one-third of nonselected tumors and the majority of estrogen and progesterone receptorpositive tumors, in advanced disease respond to endocrine therapy based on blocking estrogen receptors and/or deprivation of the estrogenic ligand.

Oophorectomy

Raloxifene

10.1093/oso/9780195135763.003.0009

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Citations (4)

Patterns of Care for Locally Advanced Pancreatic Adenocarcinoma Using the National Cancer Database

Pancreas (2017)

Arya Amini Bernard L. Jones Priscilla K. Stumpf Stephen Leong Christopher H. Lieu

Objectives The role of radiotherapy (RT) in locally advanced pancreatic cancer (LAPC) is uncertain. This study examines patterns of care and survival outcomes of LAPC undergoing chemotherapy alone versus chemotherapy plus RT (C + RT). Methods The National Cancer Database was queried for nonmetastatic LAPC patients who received chemotherapy alone or C + RT. Results Of the 13,695 patients included, 5306 underwent chemotherapy alone and 4971, C + RT. Use of C + RT declined from 2003 to 2011 (73%–53%), whereas chemotherapy alone increased. Of those receiving RT, rates of intensity-modulated radiotherapy (IMRT) increased (27%–72%), whereas 3-dimensional (3D) RT decreased (73%–28%). Unadjusted 1-year overall survival (OS) was longer for versus chemotherapy (45.6% vs 38.7%), as was 2-year OS (12.9% vs 11.9%) (hazard ratio, 0.88; 0.85–0.91; P < 0.001). Under multivariate analysis, C + RT was associated with improved OS (hazard ratio, 0.84; 0.81–0.87; P < 0.001). On subgroup analysis comparing C + IMRT, C + 3D RT, and chemotherapy alone, 1-year OS was 49.1%, 45.1%, and 38.7%, and 2-year OS was 13.1%, 11.6%, and 11.9% accordingly. Conclusions Utilization of RT in LAPC is decreasing, whereas chemotherapy alone is increasing. Of patients undergoing RT, rates of IMRT are increasing. Whereas C + IMRT appeared to be associated with improved OS compared with chemotherapy alone, 3D RT was not.

10.1097/mpa.0000000000000876

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Citations (13)

Module structure of interphotoreceptor retinoid-binding protein (IRBP) may provide bases for its complex role in the visual cycle – structure/function study of Xenopus IRBP

BMC Biochemistry (2007)

Federico Gonzalez‐Fernandez Claxton Baer Debashis Ghosh

Interphotoreceptor retinoid-binding protein's (IRBP) remarkable module structure may be critical to its role in mediating the transport of all-trans and 11-cis retinol, and 11-cis retinal between rods, cones, RPE and Müller cells during the visual cycle. We isolated cDNAs for Xenopus IRBP, and expressed and purified its individual modules, module combinations, and the full-length polypeptide. Binding of all-trans retinol, 11-cis retinal and 9-(9-anthroyloxy) stearic acid were characterized by fluorescence spectroscopy monitoring ligand-fluorescence enhancement, quenching of endogenous protein fluorescence, and energy transfer. Finally, the X-ray crystal structure of module-2 was used to predict the location of the ligand-binding sites, and compare their structures among modules using homology modeling. The full-length Xenopus IRBP cDNA codes for a polypeptide of 1,197 amino acid residues beginning with a signal peptide followed by four homologous modules each ~300 amino acid residues in length. Modules 1 and 3 are more closely related to each other than either is to modules 2 and 4. Modules 1 and 4 are most similar to the N- and C-terminal modules of the two module IRBP of teleosts. Our data are consistent with the model that vertebrate IRBPs arose through two genetic duplication events, but that the middle two modules were lost during the evolution of the ray finned fish. The sequence of the expressed full-length IRBP was confirmed by liquid chromatography-tandem mass spectrometry. The recombinant full-length Xenopus IRBP bound all-trans retinol and 11-cis retinaldehyde at 3 to 4 sites with K d 's of 0.2 to 0.3 μM, and was active in protecting all-trans retinol from degradation. Module 2 showed selectivity for all-trans retinol over 11-cis retinaldehyde. The binding data are correlated to the results of docking of all-trans-retinol to the crystal structure of Xenopus module 2 suggesting two ligand-binding sites. However, homology modeling of modules 1, 3 and 4 indicate that both sites may not be available for binding of ligands in all four modules. Although its four modules are homologous and each capable of supporting ligand-binding activity, structural differences between their ligand-binding domains, and interactions between the modules themselves will be critical to understanding IRBP's complex role in the visual cycle.

10.1186/1471-2091-8-15

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Citations (21)

FLJ/P1 Is a New Mitochondrial Dehydrogenase Important in Respiration and Apoptosis.

Blood (2006)

Lionel Coignet Timothy R. Johnson Alain Nganga Pushpankur Ghoshal Christiane Houde

clone (Java method)

10.1182/blood.v108.11.4292.4292

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Citations (0)

Aromatase and steroid sulfatase from human placenta

Methods in enzymology on CD-ROM/Methods in enzymology (2023)