GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • American Association for Cancer Research (AACR)  (16)
  • English  (16)
Material
Publisher
  • American Association for Cancer Research (AACR)  (16)
Person/Organisation
Language
  • English  (16)
Years
Subjects(RVK)
  • 1
    Online Resource
    Online Resource
    Deep Sequencing of T-cell Receptor DNA as a Biomarker of Clonally Expanded TILs in Breast Cancer after Immunotherapy
    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Immunology Research Vol. 4, No. 10 ( 2016-10-01), p. 835-844
    Details
    In: Cancer Immunology Research, American Association for Cancer Research (AACR), Vol. 4, No. 10 ( 2016-10-01), p. 835-844
    Abstract: In early-stage breast cancer, the degree of tumor-infiltrating lymphocytes (TIL) predicts response to chemotherapy and overall survival. Combination immunotherapy with immune checkpoint antibody plus tumor cryoablation can induce lymphocytic infiltrates and improve survival in mice. We used T-cell receptor (TCR) DNA sequencing to evaluate both the effect of cryoimmunotherapy in humans and the feasibility of TCR sequencing in early-stage breast cancer. In a pilot clinical trial, 18 women with early-stage breast cancer were treated preoperatively with cryoablation, single-dose anti–CTLA-4 (ipilimumab), or cryoablation + ipilimumab. TCRs within serially collected peripheral blood and tumor tissue were sequenced. In baseline tumor tissues, T-cell density as measured by TCR sequencing correlated with TIL scores obtained by hematoxylin and eosin (H & E) staining. However, tumors with little or no lymphocytes by H & E contained up to 3.6 × 106 TCR DNA sequences, highlighting the sensitivity of the ImmunoSEQ platform. In this dataset, ipilimumab increased intratumoral T-cell density over time, whereas cryoablation ± ipilimumab diversified and remodeled the intratumoral T-cell clonal repertoire. Compared with monotherapy, cryoablation plus ipilimumab was associated with numerically greater numbers of peripheral blood and intratumoral T-cell clones expanding robustly following therapy. In conclusion, TCR sequencing correlates with H & E lymphocyte scoring and provides additional information on clonal diversity. These findings support further study of the use of TCR sequencing as a biomarker for T-cell responses to therapy and for the study of cryoimmunotherapy in early-stage breast cancer. Cancer Immunol Res; 4(10); 835–44. ©2016 AACR.
    Type of Medium: Online Resource
    ISSN: 2326-6066 , 2326-6074
    URL: Article
    DOI: 10.1158/2326-6066.CIR-16-0013
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
    detail.hit.zdb_id: 2732517-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    A Pilot Study of Preoperative Single-Dose Ipilimumab and/or Cryoablation in Women with Early-Stage Breast Cancer with Comprehensive Immune Profiling
    American Association for Cancer Research (AACR) ; 2016
    In:  Clinical Cancer Research Vol. 22, No. 23 ( 2016-12-01), p. 5729-5737
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 22, No. 23 ( 2016-12-01), p. 5729-5737
    Abstract: Purpose: To assess the safety and tolerability of preoperative cryoablation-mediated tumor antigen presentation and/or ipilimumab-mediated immune modulation in women with operable breast cancer. Experimental Design: In this pilot study, 19 women with breast cancer for whom mastectomy was planned were treated with preoperative tumor cryoablation (n = 7), single-dose ipilimumab at 10 mg/kg (n = 6), or both (n = 6). The primary outcome for this pilot study was safety/tolerability as defined as freedom from delays in pre-planned, curative-intent mastectomy. Exploratory studies of immune activation were performed on peripheral blood and tumor. Results: Preoperative cryoablation and/or ipilimumab were safe and tolerable, with no delays in pre-planned surgery. Grade III toxicity was seen in 1 of 19 (unrelated rash after ipilimumab). Combination therapy was associated with sustained peripheral elevations in: Th1-type cytokines, activated (ICOS+) and proliferating (Ki67+) CD4+ and CD8+ T cells, and posttreatment proliferative T-effector cells relative to T-regulatory cells within tumor. Conclusions: Preoperative cryoablation and single-dose ipilimumab are safe alone or in combination with no surgical delays incurred. Potentially favorable intratumoral and systemic immunologic effects were observed with the combination, suggesting the possibility for induced and synergistic antitumor immunity with this strategy. Clin Cancer Res; 22(23); 5729–37. ©2016 AACR.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-16-0190
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Abstract 4509: Clinical genomic profiling of 1000 metastatic breast cancer patients: actionable targets, novel alterations, and clinical correlations
    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Research Vol. 76, No. 14_Supplement ( 2016-07-15), p. 4509-4509
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 14_Supplement ( 2016-07-15), p. 4509-4509
    Abstract: Most large genomic profiling efforts in breast cancer have focused on primary breast tumors. Profiling of metastatic breast cancer (MBC) could more accurately define actionable genomic alterations and reveal novel alterations that arise under the selective pressure and clonal evolution of prior therapy. Utilizing a 410-gene targeted capture-based sequencing platform (MSK-IMPACT), we analyzed 920 tumors (62% metastatic, 38% primary) from 874 MBC patients for somatic mutations, DNA copy number alterations, and structural rearrangements (planned final analysis 1000 patients). Detailed clinical data including treatment outcomes was collected for all patients. The cohort was representative of the well characterized clinical subtypes of breast cancer with 71% ER+ or PR+ and HER2-, 17% HER2+, and 12% triple negative breast cancer (TNBC). Our analysis revealed recurrent alterations in multiple pathways including PI3K/AKT/mTOR (56%), cell cycle regulation (42%), RTK signaling (40%), epigenetic regulation (33%) and MAPK/ERK (19%) pathways. The most frequent actionable alterations include: PIK3CA mutation (36%), ERBB2 amplification (15%), FGFR1 amplification (12%), ESR1 mutation (11%), PTEN mutation/deletion (10%), AKT1 mutation (6%), and ERBB2 mutation (5%). The genomic landscape was significantly different across breast cancer subtypes. For example, the PI3K/AKT/mTOR pathway was altered in ER+ MBC mainly through activating PIK3CA mutations whereas PTEN deletion/mutations were most common in TNBC. We also identified significant differences in the genomic profiles of metastatic and primary tumor samples. Gene enrichment analyses revealed a subset of genes more frequently altered in metastatic tumors (STK11: 13 vs 2; ROS1: 14 vs 2; FGFR4: 15 vs 1) suggesting that mutations in these genes may play a role in breast tumor metastasis and/or therapy resistance. ESR1 mutations were predominantly present in metastatic tumors (88%) and were significantly associated with duration of prior hormonal therapy (P & lt;0.0001). ESR1 mutations were also associated with a poor response to the ER degrader fulvestrant (median PFS: 4.8 vs 13.7 months, mutated vs wild type; P = 0.01). Analysis for potentially novel hotspot mutations revealed recurrent RHOA G17 mutations in 6 MBC patients, nominating RHOA, a GTPase transducer of membrane receptors, as a candidate driver in a subset of breast cancers. While identified previously in other tumors, RHOA G17 has never been implicated in breast cancer. In summary, our genomic analyses of this large cohort of MBC patients revealed actionable alterations in over 60% of the patients. 29% of patients with these alterations were enrolled in clinical trials of matched targeted therapies to date (PIK3CA 27%, AKT1 30%, ESR1 23%, ERBB2 39%) suggesting that prospective genomic characterization can accelerate enrollment of patients with MBC onto therapeutic clinical trials. Citation Format: Pedram Razavi, Matthew T. Chang, Sumit Middha, Dara S. Ross, Ahmet Zehir, Tracy A. Proverbs-Singh, Cyriac Kandoth, Sarat Chandarlapaty, Maura N. Dickler, Jorge S. Reis-Filho, Sujata Patil, Venkatraman Seshan, Lillian Smyth, Neil M. Iyengar, Komal Jhaveri, Shanu Modi, Chau T. Dang, Mark E. Robson, Larry Norton, Clifford A. Hudis, Marc Ladanyi, Maurizio Scaltriti, Nikolaus Schultz, David Hyman, Michael F. Berger, Barry S. Taylor, David B. Solit, José Baselga. Clinical genomic profiling of 1000 metastatic breast cancer patients: actionable targets, novel alterations, and clinical correlations. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4509.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2016-4509
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Effect of Differing Levels of Tobacco-Specific Nitrosamines in Cigarette Smoke on the Levels of Biomarkers in Smokers
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 19, No. 6 ( 2010-06-01), p. 1389-1398
    Details
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 19, No. 6 ( 2010-06-01), p. 1389-1398
    Abstract: Background: Smokers are exposed to significant doses of carcinogens, including tobacco-specific nitrosamines (TSNA). Previous studies have shown significant global differences in the levels of TSNAs in cigarette smoke because of the variation in tobacco blending and curing practices around the world. Methods: Mouth-level exposure to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) measured in cigarette butts and urinary concentrations of its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) were examined among 126 daily smokers in four countries over a 24-hour study period. Results: As mouth-level exposure of NNK increased, the urinary NNAL increased even after adjustment for other covariates (β = 0.46, P = 0.004). The relationship between mouth-level exposure to nicotine and its salivary metabolite, cotinine, was not statistically significant (β = 0.29, P = 0.057), likely because of the very limited range of differences in mouth-level nicotine exposure in this population. Conclusions: We have shown a direct association between the 24-hour mouth-level exposure of NNK resulting from cigarette smoking and the concentration of its primary metabolite, NNAL, in the urine of smokers. Internal dose concentrations of urinary NNAL are significantly lower in smokers in countries that have lower TSNA levels in cigarettes such as Canada and Australia in contrast to countries that have high levels of these carcinogens in cigarettes, such as the United States. Impact: Lowering the levels of NNK in the mainstream smoke of cigarettes through the use of specific tobacco types and known curing practices can significantly affect the exposure of smokers to this known carcinogen. Cancer Epidemiol Biomarkers Prev; 19(6); 1389–98. ©2010 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    URL: Article
    DOI: 10.1158/1055-9965.EPI-10-0084
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Fetal Mouse Cyp1b1 and Transplacental Carcinogenesis from Maternal Exposure to Dibenzo( a,l )pyrene
    American Association for Cancer Research (AACR) ; 2008
    In:  Cancer Prevention Research Vol. 1, No. 2 ( 2008-07-01), p. 128-134
    Details
    In: Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 1, No. 2 ( 2008-07-01), p. 128-134
    Abstract: Dibenzo(a,l)pyrene (DBP) is among the most potent carcinogenic polycyclic aromatic hydrocarbons. Previously, we showed that DBP administration to pregnant mice resulted in high mortality of offspring from an aggressive T-cell lymphoma. All mice that survive to 10 months of age exhibit lung tumors with high multiplicity. Recombinant cytochrome P450 (cyp) 1b1 from mice and the homologue 1B1 in humans exhibit high activity toward the metabolic activation of DBP. Targeted disruption of the cyp1b1 gene protects against most DBP-dependent cancers. Mice heterozygous for the disrupted cyp1b1 allele were used to examine the effect of cyp1b1 gene dosage on DBP transplacental carcinogenesis. Dams were treated with 1 or 15 mg/kg of DBP or 50 mg/kg of benzo(a)pyrene. Cyp1b1-null offspring did not develop lymphoma, whereas wild-type and heterozygous siblings, born to dams given the high dose of DBP, exhibited significant mortalities between 10 and 30 weeks of age. At 10 months, all groups had lung adenomas or carcinomas [9.5%, 40.3%, 25.6%, and 100% incidences for controls, benzo(a)pyrene, 1 and 15 mg/kg DBP, respectively]. Cyp1b1 status did not alter benzo(a)pyrene-dependent carcinogenesis. At 1 mg/kg DBP, cyp1b1 status altered the incidence of lung tumors (19.0, 27.8, and 28.6% for nulls, heterozygous, and wild-type, respectively). At 15 mg/kg, tumor multiplicities in cyp1b1 wild-type (9.3) and heterozygous (9.5) offspring were nearly twice that of cyp1b1-null siblings (5.0). These data confirm that cyp1b1 bioactivation of DBP occurs in fetal target tissues, following transplacental exposure, with the thymus and lung as primary and secondary targets, respectively.
    Type of Medium: Online Resource
    ISSN: 1940-6207 , 1940-6215
    URL: Article
    DOI: 10.1158/1940-6207.CAPR-07-0004
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2008
    detail.hit.zdb_id: 2422346-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Levels of Tobacco-Specific Nitrosamines and Polycyclic Aromatic Hydrocarbons in Mainstream Smoke from Different Tobacco Varieties
    American Association for Cancer Research (AACR) ; 2008
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 17, No. 12 ( 2008-12-01), p. 3366-3371
    Details
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 17, No. 12 ( 2008-12-01), p. 3366-3371
    Abstract: It has been estimated that one in every five cancer deaths worldwide are related to tobacco use. According to the IARC, 10 polycyclic aromatic hydrocarbons (PAH) and 8 tobacco-specific nitrosamines (TSNA), as well as at least 45 other compounds or substances found in tobacco smoke, are potential human carcinogens. The levels of these carcinogens in contents of tobacco and smoke emissions vary between different tobacco products. We evaluated mainstream smoke emissions from cigarettes made with different types of tobacco to examine the relation between their deliveries of TSNAs and PAHs and any possible influence from tobacco nitrate content. To investigate the contribution of tobacco content to mainstream cigarette smoke deliveries without confounders such as filter design, filter ventilation, and paper porosity, we used custom-made, research-grade, unfiltered cigarettes that contained bright, burley, oriental, reconstituted, or mixtures of these tobaccos. Our findings confirm results from other researchers that tobacco type can influence the mainstream smoke delivery of nicotine, TSNAs, and PAHs. However, we found that the effect varies among individual compounds. In addition, we observed a statistically significant relationship between nitrate content and mainstream smoke 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK); nitrate level also influenced the mainstream smoke deliveries of the summed total of the 10 PAHs identified by IARC as potential human carcinogens. The influence of nitrate on mainstream smoke NNK and PAH levels were of different magnitude and direction. Our results tend to indicate an inverse relation exists between NNK and PAH deliveries when considering different tobacco blends. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3366–71)
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    URL: Article
    DOI: 10.1158/1055-9965.EPI-08-0320
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2008
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Pathologic Correlates of Primary Central Nervous System Lymphoma Defined in an Orthotopic Xenograft Model
    American Association for Cancer Research (AACR) ; 2009
    In:  Clinical Cancer Research Vol. 15, No. 6 ( 2009-03-15), p. 1989-1997
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 15, No. 6 ( 2009-03-15), p. 1989-1997
    Abstract: Purpose: The prospect for advances in the treatment of patients with primary central nervous system lymphoma (PCNSL) is likely dependent on the systematic evaluation of its pathobiology. Animal models of PCNSL are needed to facilitate the analysis of its molecular pathogenesis and for the efficient evaluation of novel therapeutics. Experimental Design: We characterized the molecular pathology of CNS lymphoma tumors generated by the intracerebral implantation of Raji B lymphoma cells in athymic mice. Lymphoma cells were modified for bioluminescence imaging to facilitate monitoring of tumor growth and response to therapy. In parallel, we identified molecular features of lymphoma xenograft histopathology that are evident in human PCNSL specimens. Results: Intracerebral Raji tumors were determined to faithfully reflect the molecular pathogenesis of PCNSL, including the predominant immunophenotypic state of differentiation of lymphoma cells and their reactive microenvironment. We show the expression of interleukin-4 by Raji and other B lymphoma cell lines in vitro and by Raji tumors in vivo and provide evidence for a role of this cytokine in the M2 polarization of lymphoma macrophages both in the murine model and in diagnostic specimens of human PCNSL. Conclusion: Intracerebral implantation of Raji cells results in a reproducible and invasive xenograft model, which recapitulates the histopathology and molecular features of PCNSL, and is suitable for preclinical testing of novel agents. We also show for the first time the feasibility and accuracy of tumor bioluminescence in the monitoring of a highly infiltrative brain tumor.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-08-2054
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2009
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    A Genomically and Clinically Annotated Patient-Derived Xenograft Resource for Preclinical Research in Non–Small Cell Lung Cancer
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 22 ( 2022-11-15), p. 4126-4138
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 22 ( 2022-11-15), p. 4126-4138
    Abstract: Patient-derived xenograft (PDX) models are an effective preclinical in vivo platform for testing the efficacy of novel drugs and drug combinations for cancer therapeutics. Here we describe a repository of 79 genomically and clinically annotated lung cancer PDXs available from The Jackson Laboratory that have been extensively characterized for histopathologic features, mutational profiles, gene expression, and copy-number aberrations. Most of the PDXs are models of non–small cell lung cancer (NSCLC), including 37 lung adenocarcinoma (LUAD) and 33 lung squamous cell carcinoma (LUSC) models. Other lung cancer models in the repository include four small cell carcinomas, two large cell neuroendocrine carcinomas, two adenosquamous carcinomas, and one pleomorphic carcinoma. Models with both de novo and acquired resistance to targeted therapies with tyrosine kinase inhibitors are available in the collection. The genomic profiles of the LUAD and LUSC PDX models are consistent with those observed in patient tumors from The Cancer Genome Atlas and previously characterized gene expression-based molecular subtypes. Clinically relevant mutations identified in the original patient tumors were confirmed in engrafted PDX tumors. Treatment studies performed in a subset of the models recapitulated the responses expected on the basis of the observed genomic profiles. These models therefore serve as a valuable preclinical platform for translational cancer research. Significance: Patient-derived xenografts of lung cancer retain key features observed in the originating patient tumors and show expected responses to treatment with standard-of-care agents, providing experimentally tractable and reproducible models for preclinical investigations.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-22-0948
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    In utero Exposure of Mice to Dibenzo[ a,l ]Pyrene Produces Lymphoma in the Offspring: Role of the Aryl Hydrocarbon Receptor
    American Association for Cancer Research (AACR) ; 2006
    In:  Cancer Research Vol. 66, No. 2 ( 2006-01-15), p. 755-762
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 66, No. 2 ( 2006-01-15), p. 755-762
    Abstract: Lymphoma and leukemia are the most common cancers in children and young adults; in utero carcinogen exposure may contribute to the etiology of these cancers. A polycyclic aromatic hydrocarbon (PAH), dibenzo[a,l] pyrene (DBP), was given to pregnant mice (15 mg/kg body weight, gavage) on gestation day 17. Significant mortalities in offspring, beginning at 12 weeks of age, were observed due to an aggressive T-cell lymphoblastic lymphoma. Lymphocytes invaded numerous tissues. All mice surviving 10 months, exposed in utero to DBP, exhibited lung tumors; some mice also had liver tumors. To assess the role of the aryl hydrocarbon receptor (AHR) in DBP transplacental cancer, B6129SF1/J (AHRb-1/d, responsive) mice were crossed with strain 129S1/SvIm (AHRd/d, nonresponsive) to determine the effect of maternal and fetal AHR status on carcinogenesis. Offspring born to nonresponsive mothers had greater susceptibility to lymphoma, irrespective of offspring phenotype. However, when the mother was responsive, an AHR-responsive phenotype in offspring increased mortality by 2-fold. In DBP-induced lymphomas, no evidence was found for TP53, β-catenin, or Ki-ras mutations but lung adenomas of mice surviving to 10 months of age had mutations in Ki-ras codons 12 and 13. Lung adenomas exhibited a 50% decrease and a 35-fold increase in expression of Rb and p19/ARF mRNA, respectively. This is the first demonstration that transplacental exposure to an environmental PAH can induce a highly aggressive lymphoma in mice and raises the possibility that PAH exposures to pregnant women could contribute to similar cancers in children and young adults. (Cancer Res 2006; 66(2): 755-62)
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-05-3390
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2006
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    p53 Expression in Node-Positive Breast Cancer Patients: Results from the Cancer and Leukemia Group B 9344 Trial (159905)
    American Association for Cancer Research (AACR) ; 2011
    In:  Clinical Cancer Research Vol. 17, No. 15 ( 2011-08-01), p. 5170-5178
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 17, No. 15 ( 2011-08-01), p. 5170-5178
    Abstract: Purpose: p53 as a prognostic and predictive factor in early-stage breast cancer has had mixed results. We studied p53 protein expression, by immunohistochemistry, in a randomized clinical trial of stage II patients treated with adjuvant doxorubicin and cyclophosphamide with or without paclitaxel [Cancer and Leukemia Group B (CALGB) 9344, INT0148]. Patients and Methods: Epithelial p53 expression was evaluated using two immunohistochemical antibodies (DO7 and 1801) in formalin-fixed, paraffin-embedded tissue from patients with node-positive breast cancer who were randomized to four cycles of cyclophosphamide and one of three doses of doxorubicin (60, 75, or 90 mg/m2; AC) and to receive four subsequent cycles of paclitaxel (T) or not. Prognostic and predictive value of p53 protein expression was assessed, independent of treatment assignment, for escalating doses of doxorubicin or addition of T with endpoints of relapse-free (RFS) and overall survival (OS). Results: Of 3,121 patients, 1,887 patient specimens treated on C9344 were obtained, passed quality control, and evaluated for p53 expression. Expression was 23% and 27% for mAbs 1801 and D07, respectively, with 92% concordance. In univariate analysis, p53 positivity was associated with worse OS with either antibody, but only p53 staining with monoclonal antibody 1801 had significantly worse RFS. In multivariate analysis, p53 was not predictive of RFS or OS from either doxorubicin dose escalation or addition of paclitaxel regardless of the antibody. Conclusion: Nuclear staining of p53 by immunohistochemistry is associated with worse prognosis in node-positive patients treated with adjuvant doxorubicin-based chemotherapy but is not a useful predictor of benefit from doxorubicin dose escalation or the addition of paclitaxel. Clin Cancer Res; 17(15); 5170–8. ©2011 AACR.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-11-0484
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...