Abstract:
:Cancer relapse after surgery is a common occurrence, most frequently resulting from the outgrowth of minimal residual disease in the form of metastases. We examined the effectiveness of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockade as an adjunctive immunotherapy to reduce metastatic relapse after primary prostate tumor resection. For these studies, we developed a murine model in which overt metastatic outgrowth of TRAMP-C2 (C2) prostate cancer ensues after complete primary tumor resection. Metastatic relapse in this model occurs reliably and principally within the draining lymph nodes in close proximity to the primary tumor, arising from established metastases present at the time of surgery. Using this model, we demonstrate that adjunctive CTLA-4 blockade administered immediately after primary tumor resection reduces metastatic relapse from 97.4 to 44%. Consistent with this, lymph nodes obtained 2 weeks after treatment reveal marked destruction or complete elimination of C2 metastases in 60% of mice receiving adjunctive anti-CTLA-4 whereas 100% of control antibody-treated mice demonstrate progressive C2 lymph node replacement. Our study demonstrates the potential of adjunctive CTLA-4 blockade immunotherapy to reduce cancer relapse emanating from minimal residual metastatic disease and may have broader implications for improving the capability of immunotherapy by combining such forms of therapy with other cytoreductive measures including surgery.
journal_name
Proc Natl Acad Sci U S Aauthors
Kwon ED,Foster BA,Hurwitz AA,Madias C,Allison JP,Greenberg NM,Burg MBdoi
10.1073/pnas.96.26.15074keywords:
subject
Has Abstractpub_date
1999-12-21 00:00:00pages
15074-9issue
26eissn
0027-8424issn
1091-6490journal_volume
96pub_type
杂志文章abstract::A single animal group can display different types of collective motion at different times. For a one-dimensional individual-based model of self-organizing group formation, we show that repeated switching between distinct ordered collective states can occur entirely because of stochastic effects. We introduce a framewo...
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.0608270104
更新日期:2007-04-03 00:00:00
abstract::The seventh cholera pandemic caused by Vibrio cholerae O1 El Tor (ET) has been superseded in Asia and Africa by altered ET possessing the cholera toxin (CTX) gene of classical (CL) biotype. The CL biotype of V. cholerae was isolated, along with prototypic and altered ET, during the 1991 cholera epidemic in Mexico and ...
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.1323408111
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abstract::ATP-dependent DNA supercoiling catalyzed by Escherichia coli DNA gyrase was inhibited by oxolinic acid, a compound similar to but more potent than nalidixic acid and a known inhibitor of DNA replication in E. coli. The supercoiling activity of DNA gyrase purified from nalidixic acid-resistant mutant (nalA(R)) bacteria...
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.74.11.4772
更新日期:1977-11-01 00:00:00
abstract::Salicylic acid (SA) plays an important role in activating various plant defense responses, including expression of the pathogenesis-related (PR) genes and systemic acquired resistance. A critical positive regulator of the SA signaling pathway in Arabidopsis is encoded by the NPR1 gene. However, there is growing eviden...
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.151258398
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abstract::During meiosis, homologous chromosomes recombine and become closely apposed along their lengths within the synaptonemal complex (SC). In part because Spo11 is required both to make the double-strand breaks (DSBs) that initiate recombination and to promote normal SC formation in many organisms, it is clear that these t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.0400843101
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abstract::Unambiguous evidence is presented that two X-chromosome inversions produce lethality in X/O males because of position-effect suppression of genes in the basal heterochromatin. The data support the hypothesis that the ribosomal RNA cistrons are the genes suppressed. There is evidence for a region in the X basal heteroc...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.68.10.2472
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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.90.7.3108
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abstract::Effects of thyrotropin-releasing hormone (TRH; thyroliberin) on membrane electrical properties were studied in the clonal rat anterior pituitary cell (GH3) by continuous recording of the intracellular potential. Application of TRH, which stimulates the release of prolactin and growth hormone from the GH3 cell, elicite...
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.76.11.6017
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.131153098
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abstract::Small RNAs (sRNAs) are hypothesized to contribute to hybrid vigor because they maintain genome integrity, contribute to genetic diversity, and control gene expression. We used Illumina sequencing to assess how sRNA populations vary between two maize inbred lines (B73 and Mo17) and their hybrid. We sampled sRNAs from t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2012-06-26 00:00:00
abstract::Periodicities in the polar/apolar character of the amino acid sequence of a protein can be examined by assigning to each residue a numerical hydrophobicity and searching for periodicity in the resulting one-dimensional function. The strength of each periodic component is the quantity that has been termed the hydrophob...
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.81.1.140
更新日期:1984-01-01 00:00:00
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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.1317164110
更新日期:2013-10-29 00:00:00
abstract::Epidermal growth factor (EGF) receptor monomers and noncovalently associated dimers were isolated by sucrose density gradient centrifugation, and their respective binding and autophosphorylation activities were determined. We find that monomers are low-affinity receptors and dimers are high-affinity receptors. In the ...
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.84.22.7832
更新日期:1987-11-01 00:00:00
abstract::A conformational isoform of the mammalian prion protein (PrP(Sc)) is the sole component of the infectious pathogen that causes the prion diseases. We have obtained X-ray fiber diffraction patterns from infectious prions that show cross-beta diffraction: meridional intensity at 4.8 A resolution, indicating the presence...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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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.0803728105
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.74.12.5677
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2016-12-20 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2015-09-15 00:00:00
abstract::Homozygous uniparental mouse embryos, produced by microsurgical removal of the male pronucleus from fertilized eggs and diploidization of the female pronucleus with cytochalasin, were surrounded with blastomeres from normal embryos to produce chimeric embryos. A few of these chimeras developed into viable adults, and ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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abstract::CD4+ T cells recognize major histocompatibility complex (MHC) class II-bound peptides that are primarily obtained from extracellular sources. Endogenously synthesized proteins that readily enter the MHC class I presentation pathway are generally excluded from the MHC class II presentation pathway. We show here that en...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.92.16.7217
更新日期:1995-08-01 00:00:00
abstract::Over the past 50 years, the rising tree line along Jumpingpound Ridge in the Rocky Mountains of Alberta, Canada, has reduced the area of alpine meadows and isolated populations that reside within them. By analyzing an 11-year data set of butterfly population sizes for 17 subpopulations along the ridge, we show that fo...
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.0705511104
更新日期:2007-08-21 00:00:00