Abstract:
:Mechanisms of estrogen-induced tumorigenesis in the target organ are not well understood. It has been suggested that oxidative stress resulting from metabolic activation of carcinogenic estrogens plays a critical role in estrogen-induced carcinogenesis. We tested this hypothesis by using an estrogen-induced hamster renal tumor model, a well established animal model of hormonal carcinogenesis. Hamsters were implanted with 17beta-estradiol (betaE2), 17alpha-estradiol (alphaE2), 17alpha-ethinylestradiol (alphaEE), menadione, a combination of alphaE2 and alphaEE, or a combination of alphaEE and menadione for 7 months. The group treated with betaE2 developed target organ specific kidney tumors. The kidneys of hamsters treated with alphaE2, alphaEE, or menadione alone did not show any gross evidence of tumor. Kidneys of hamsters treated with a combination of alphaE2 and alphaEE showed early signs of proliferation in the interstitial cells. Kidneys of hamsters treated with a combination of menadione and alphaEE showed foci of tumor with congested tubules and atrophic glomeruli. betaE2-treated tumor-bearing kidneys showed >2-fold increase in 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) levels compared with untreated controls. Kidneys of hamsters treated with a combination of menadione and alphaEE showed increased 8-iso-PGF(2alpha) levels compared with untreated controls, whereas no increase in 8-iso-PGF(2alpha) was detected in kidneys of alphaEE-treated group. A chemical known to produce oxidative stress or a potent estrogen with poor ability to produce oxidative stress, were nontumorigenic in hamsters, when given as single agents, but induced renal tumors, when given together. Thus, these data provide evidence that oxidant stress plays a crucial role in estrogen-induced carcinogenesis.
journal_name
Proc Natl Acad Sci U S Aauthors
Bhat HK,Calaf G,Hei TK,Loya T,Vadgama JVdoi
10.1073/pnas.0437929100keywords:
subject
Has Abstractpub_date
2003-04-01 00:00:00pages
3913-8issue
7eissn
0027-8424issn
1091-6490pii
0437929100journal_volume
100pub_type
杂志文章abstract::Excited states of proteins may play important roles in function, yet are difficult to study spectroscopically because of their sparse population. High hydrostatic pressure increases the equilibrium population of excited states, enabling their characterization [Akasaka K (2003) Biochemistry 42:10875-85]. High-pressure ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1320124110
更新日期:2013-12-03 00:00:00
abstract::We introduced radioactive precursors directly into identified neurons of Aplysia californica. [(3)H]-Choline and L-[(3)H]tryptophan were injected with pressure into nerve cell bodies to study synthesis of acetylcholine and serotonin. We confirmed the cholinergic nature of R2, L10, and L11, identified neurons of the ab...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.70.12.3371
更新日期:1973-12-01 00:00:00
abstract::The oxidative capacity of cat skeletal muscles (soleus, gracilis, and gracilis chronically stimulated for 28 days) was derived from the total mitochondrial content in the muscle, the surface area of mitochondrial inner membranes, and respiratory activities of isolated mitochondria. Mitochondrial content was estimated ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.5.1583
更新日期:1989-03-01 00:00:00
abstract::Monoclonal antibodies can block cellular interactions that negatively regulate T-cell immune responses, such as CD80/CTLA-4 and PD-1/PD1-L, amplifying preexisting immunity and thereby evoking antitumor immune responses. Ibrutinib, an approved therapy for B-cell malignancies, is a covalent inhibitor of BTK, a member of...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1500712112
更新日期:2015-03-03 00:00:00
abstract::It is proved that the well known Nagata automorphism of the polynomial ring in three variables over a field of characteristic zero is wild, that is, it can not be decomposed into a product of elementary automorphisms. ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1735483100
更新日期:2003-10-28 00:00:00
abstract::West Nile virus, which is transmitted by Culex mosquitoes while feeding on birds and humans, has emerged as the dominant vector borne disease in North America. We have identified natural compounds from humans and birds, which are detected with extreme sensitivity by olfactory receptor neurons (ORNs) on the antennae of...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0906932106
更新日期:2009-11-03 00:00:00
abstract::Bruton tyrosine kinase (EC 2.7.1.112) [Btk, encoded by Btk in mice and BTK in humans (formerly known as atk, BPK, or emb)], which is variously mutated in chromosome X-linked agammaglobulinemia patients and X-linked immunodeficient (xid) mice, has the pleckstrin homology (PH) domain at its amino terminus. The PH domain...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.19.9175
更新日期:1994-09-13 00:00:00
abstract::The "disease-specific" (dsp) region next to the hrp gene cluster of Erwinia amylovora is required for pathogenicity but not for elicitation of the hypersensitive reaction. A 6.6-kb apparent operon, dspEF, was found responsible for this phenotype. The operon contains genes dspE and dspF and is positively regulated by h...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.3.1325
更新日期:1998-02-03 00:00:00
abstract::Hormones and nutrients often induce genetic programs via signaling pathways that interface with gene-specific activators. Activation of the cAMP pathway, for example, stimulates cellular gene expression by means of the PKA-mediated phosphorylation of cAMP-response element binding protein (CREB) at Ser-133. Here, we us...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0501076102
更新日期:2005-03-22 00:00:00
abstract::A general procedure is described for the production of human monoclonal antibodies from peripheral blood lymphocytes immunized in vitro against T-cell-dependent antigens. These lymphocytes immunized in culture were used to produce human-human or human-mouse hybridomas secreting monoclonal antibodies specific for digox...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.11.3995
更新日期:1988-06-01 00:00:00
abstract::Modulation of cholesterol absorption in the intestine, the primary site of dietary cholesterol uptake in humans, can have profound clinical implications. We have undertaken a reverse genetic approach by disrupting putative cholesterol processing genes in zebrafish larvae by using morpholino (MO) antisense oligonucleot...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,收录出版
doi:10.1073/pnas.0400441101
更新日期:2004-03-09 00:00:00
abstract::Transcriptional regulation by nuclear hormone receptors is thought to involve interactions with putative cofactors that may potentiate receptor function. Here we show that human thyroid hormone receptor alpha purified from HeLa cells grown in the presence of thyroid hormone (T3) is associated with a group of distinct ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.16.8329
更新日期:1996-08-06 00:00:00
abstract::Although mind wandering occupies a large proportion of our waking life, its neural basis and relation to ongoing behavior remain controversial. We report an fMRI study that used experience sampling to provide an online measure of mind wandering during a concurrent task. Analyses focused on the interval of time immedia...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0900234106
更新日期:2009-05-26 00:00:00
abstract::Activation of the androgen receptor (AR) may play a role in androgen-independent progression of prostate cancer. Multiple mechanisms of AR activation, including stimulation by tyrosine kinases, have been postulated. We and others have recently shown involvement of activated Cdc42-associated tyrosine kinase Ack1 in adv...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0700420104
更新日期:2007-05-15 00:00:00
abstract::Fetal cells, potentially usable for prenatal diagnosis, were sorted from maternal blood samples taken as early as 15 weeks of gestation. Immunogenetic and cytogenic criteria established the fetal origin of the observed cells: Y-chromatin-containing (male) cells were detected in the sorted sample if and only if the new...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.76.3.1453
更新日期:1979-03-01 00:00:00
abstract::In adult rat testes, the blood-testis barrier (BTB) in the seminiferous epithelium must "open" (or "disassemble") to accommodate the migration of preleptotene spermatocytes from the basal to the adluminal compartment that occurs at stage VIII of the epithelial cycle. However, the molecule(s) and/or mechanism(s) that r...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0610100104
更新日期:2007-03-06 00:00:00
abstract::In nearly all eukaryotes, at least some individuals inherit mitochondrial and chloroplast genes from only one parent. There is no single mechanism of uniparental inheritance: organelle gene inheritance is blocked by a variety of mechanisms and at different stages of reproduction in different species. Frequent changes ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,评审
doi:10.1073/pnas.92.25.11331
更新日期:1995-12-05 00:00:00
abstract::We have determined the general constraints that govern sequence divergence in proteins that retain entirely, or very largely, the same structure and function. To do this we collected data from three different groups of orthologous sequences: those found in humans and mice, in humans and chickens, and in Escherichia co...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0703737104
更新日期:2007-06-12 00:00:00
abstract::Trigger factor (TF), the first chaperone in eubacteria to encounter the emerging nascent chain, binds to the large ribosomal subunit in the vicinity of the protein exit tunnel opening and forms a sheltered folding space. Here, we present the 3.5-A crystal structure of the physiological complex of the large ribosomal s...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0505581102
更新日期:2005-08-23 00:00:00
abstract::Autism spectrum disorders (ASDs) comprise a highly heritable, multifarious group of neurodevelopmental disorders, which are characterized by repetitive behaviors and impairments in social interactions. Point mutations have been identified in X-linked Neuroligin (NLGN) 3 and 4X genes in patients with ASDs and all of th...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1500501112
更新日期:2015-02-24 00:00:00
abstract::We report a measurement of the transverse momentum correlation between two photons by detecting only one of them. Our method uses two identical sources in an arrangement in which the phenomenon of induced coherence without induced emission is observed. In this way, we produce an interference pattern in the superpositi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1620979114
更新日期:2017-02-14 00:00:00
abstract::Acute glaucoma is a sight-threatening condition characterized by a sudden and substantial rise in intraocular pressure (IOP) and consequent retinal ganglion cell (RGC) death. Angle closure glaucoma, a common cause of glaucoma in Asia that affects tens of millions of people worldwide, often presents acutely with loss o...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1402819111
更新日期:2014-07-29 00:00:00
abstract::A hallmark of the pathology of Alzheimer's disease is the accumulation of the microtubule-associated protein tau into fibrillar aggregates. Recent studies suggest that they accumulate because cytosolic chaperones fail to clear abnormally phosphorylated tau, preserving a pool of toxic tau intermediates within the neuro...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0709180105
更新日期:2008-03-04 00:00:00
abstract::The transcription factor retinoic acid receptor beta(2) (RARbeta(2)) is a potent inhibitor of breast cancer cells in vitro, and studies suggest that RARbeta expression is lost in primary breast cancer. Although RARbeta(2) is selectively down-regulated at the mRNA level in breast tumor cells, we show that expression of...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.15.8651
更新日期:1999-07-20 00:00:00
abstract::The Bam complex assembles β-barrel proteins into the outer membrane (OM) of Gram-negative bacteria. These proteins comprise cylindrical β-sheets with long extracellular loops and create pores to allow passage of nutrients and waste products across the membrane. Despite their functional importance, several questions re...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1616576114
更新日期:2017-03-07 00:00:00
abstract::From the types of ring chromosomes induced in x-irradiated Chinese hamster ovary (CHO) cells, we deduce the existence of switches in the polarity of chromosomal DNA; if there is a continuous DNA double helix along the full length of the chromosome then the polarity switches imply 3'-3' and 5'-5' phosphodiester linkage...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.73.3.877
更新日期:1976-03-01 00:00:00
abstract::The only known product of the Snyder-Theilen strain of feline sarcoma virus (ST-FeSV) is a 85,000-dalton protein, designated ST P85, that contains feline leukemia virus gag gene encoded proteins (p15, p12, and a fragment of p30) and a sarcoma virus-specific polypeptide. Antibodies directed against the latter immunopre...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.9.5158
更新日期:1980-09-01 00:00:00
abstract::Pseudomonas aeruginosa is an opportunistic pathogen that requires preexisiting epithelial injury to cause acute infections. We report that P. aeruginosa inhibits mammalian cytokinesis in a type III secretion system and exotoxin T (ExoT)-dependent manner. ExoT is a bifunctional type III secretion system effector protei...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0605949103
更新日期:2006-10-17 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) is characterized by the presence of abundant desmoplastic stroma primarily composed of cancer-associated fibroblasts (CAFs). It is generally accepted that CAFs stimulate tumor progression and might be implicated in drug resistance and immunosuppression. Here, we have compared th...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1717802115
更新日期:2018-02-06 00:00:00
abstract::Organic agriculture promotes sustainability compared to conventional agriculture. However, the multifunctional sustainability benefits of organic farms might be mediated by landscape context. Assessing how landscape context affects sustainability may aid in targeting organic production to landscapes that promote high ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1906909117
更新日期:2020-02-11 00:00:00