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  • American Association for Cancer Research (AACR)  (3)
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  • American Association for Cancer Research (AACR)  (3)
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  • 1
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2004
    In:  Clinical Cancer Research Vol. 10, No. 20 ( 2004-10-15), p. 6887-6896
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 10, No. 20 ( 2004-10-15), p. 6887-6896
    Abstract: Purpose: French-American-British (FAB) classification of acute leukemia with genetic heterogeneity is important for treatment and prognosis. However, the distinct protein profiles that contribute to the subtypes and facilitate molecular definition of acute leukemia classification are still unclear. Experimental Design: The proteins of leukemic cells from 61 cases of acute leukemia characterized by FAB classification were separated by two-dimensional electrophoresis, and the differentially expressed protein spots were identified by both matrix-assisted laser desorption/ionization–time-of-flight–mass spectrometry (MALDI-TOF-MS) and tandem electrospray ionization MS (ESI-MS/MS). Results: The distinct protein profiles of acute leukemia FAB types or subtypes were successfully explored, including acute myeloid leukemia (AML), its subtypes (M2, M3, and M5) and acute lymphoid leukemia (ALL), which were homogeneous within substantial samples of the respective subgroups but clearly differed from all other subgroups. We found a group of proteins that were highly expressed in M2 and M3, rather than other subtypes. Among them, myeloid-related proteins 8 and 14 were first reported to mark AML differentiation and to differentiate AML from ALL. Heat shock 27 kDa protein 1 and other proteins that are highly expressed in ALL may play important roles in clinically distinguishing AML from ALL. Another set of proteins up-regulated was restricted to granulocytic lineage leukemia. High-level expression of NM23-H1 was found in all but the M3a subtype, with favorable prognosis. Conclusions: These data have implications in delineating the pathways of aberrant gene expression underlying the pathogenesis of acute leukemia and could facilitate molecular definition of FAB classification. The extension of the present analysis to currently less well-defined acute leukemias will identify additional subgroups.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2004
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 2
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 4_Supplement ( 2022-02-15), p. P2-10-10-P2-10-10
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. P2-10-10-P2-10-10
    Abstract: Background: Brain metastasis (BM) was traditionally considered to occur in the terminal stage of breast cancer (BC) and be associated with large tumor size and nodal involvement. However, evidence suggests in triple-negative BC patients, the effects of T stage and N stage on the risk of BM were not prominent. Besides, recent studies have identified some overlap in gene expression profiles between brain and lung metastasis, but further validation in clinical settings is lacking. Therefore, one objective of our study was to determine the risk factors associated with BM in BC patients on a population-based level, focusing on the relationship between extracranial metastasis and BM. We also intended to investigate whether the associations differ across different strata by evaluating the interactions among risk factors of BM. Methods: The Surveillance, Epidemiology, and End Results database was used to select BC patients diagnosed from 2010 to 2018. We calculated the incidence proportions of BM and performed univariate and multivariate logistic regression analyses to estimate odds ratios (ORs) and 95% confidence intervals (CI) for analyses of potential risk factors of BM. Interactive effects of any suspected risk factors were evaluated using a multiplicative interaction term and adjusting for all covariates. After the statistical interactions were found, we performed stratified analyses to further test the relationships between two risk factors. Results: A total of 527,525 BC patients were selected. For patients with only one extracranial metastatic site, lung was the most common metastatic site (6.37%), followed by bone (4.12%) and liver (3.42%). Multivariate logistic regression analysis among the whole population showed age, subtype, grade, T stage, N stage, histology, and pattern of extracranial metastasis are independent predictors of BM, while sex, race, and laterality did not significantly influence risks of BM. We found significant interactions between subtype and T stage (p = 0.004) and between subtype and N stage (p = 0.002) that increased the risk of BM. In stratified analyses, the associations of BM with T stage were significant in all subtypes except HR-/HER2- (Table 1). Only in HR+/HER2+ and HR-/HER2- patients, the associations of N stage with BM were significant (p & lt; 0.001 for both groups). The associations of T stage and N stage with BM did not differ by age. For patients with only one extracranial metastatic site, pattern of extracranial metastasis significantly interacted with subtype (p = 0.013). The association of extracranial metastatic pattern with BM was significant only among HR-/HER2- patients. Compared to patients with extracranial metastasis only to the bone, patients with extracranial metastasis only to the liver had a lower risk of BM (OR = 0.455, 95% CI: 0.219-0.948, p = 0.035), while patients with extracranial metastasis only to the lung had a higher risk of BM (OR = 1.936, 95% CI: 1.300-2.882, p = 0.001). Conclusion: Breast subtypes can modify the associations of BM with tumor size, nodal status, and pattern of extracranial metastasis. Risk elevations with higher T stage are significant among all subtypes except HR-/HER2-, indicating BM in HR-/HER2- patients may not be driven by larger tumor size. HR-/HER2- patients with lung metastasis are more susceptible to BM, providing clinical evidence for pathway overlap between brain and lung metastases. Table 1.Stratified associations between T stage and brain metastasismultivariable-adjusted OR (95% CI)p for trendp for interactionT1T2T3T4T-unknownSubtype0.004HR+/HER2-Reference1.550 (1.221-1.968)1.641 (1.227-2.194)1.816 (1.399-2.358)2.097 (1.575-2.793) & lt; 0.001HR+/HER2+Reference0.979 (0.660-1.452)1.185 (0.741-1.894)1.605 (1.065-2.418)1.686 (1.048-2.712)0.009HR-/HER2+Reference1.410 (0.862-2.305)1.187 (0.658-2.141)1.733 (1.050-2.858)3.489 (2.030-5.998) & lt; 0.001HR-/HER2-Reference0.993 (0.701-1.407)1.300 (0.863-1.958)1.402 (0.959-2.052)1.499 (0.940-2.388)0.126 Citation Format: Bo Shen, Jieqing Li, Mei Yang, Junsheng Zhang, Weiping Li, Kun Wang. The associations between brain metastasis and tumor size, nodal status, and patterns of extracranial metastasis vary by subtypes in breast cancer patients: A population-based study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-10-10.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    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
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  • 3
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2014
    In:  Clinical Cancer Research Vol. 20, No. 6 ( 2014-03-15), p. 1489-1501
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 20, No. 6 ( 2014-03-15), p. 1489-1501
    Abstract: Purpose: Human DNA topoisomerase III alpha (hTOP3α) is involved in DNA repair surveillance and cell-cycle checkpoints possibly through formatting complex with tumor suppressors. However, its role in cancer development remained unsolved. Experimental Design: Coimmunoprecipitation, sucrose gradient, chromatin immunoprecipitation (ChIP), real time PCR, and immunoblotting analyses were performed to determine interactions of hTOP3α with p53. Paired cell lines with different hTOP3α levels were generated via ectopic expression and short hairpin RNA (shRNA)-mediated knockdown approaches. Cellular tumorigenic properties were analyzed using cell counting, colony formation, senescence, soft agar assays, and mouse xenograft models. Results: The hTOP3α isozyme binds to p53 and cofractionizes with p53 in gradients differing from fractions containing hTOP3α and BLM. Knockdown of hTOP3α expression (sh-hTOP3α) caused a higher anchorage-independent growth of nontumorigenic RHEK-1 cells. Similarly, sh-hTOP3α and ectopic expression of hTOP3α in cancer cell lines caused increased and reduced tumorigenic abilities, respectively. Genetic and mutation experiments revealed that functional hTOP3α, p53, and p21 are required for this tumor-suppressive activity. Mechanism-wise, ChIP data revealed that hTOP3α binds to the p53 and p21 promoters and positively regulates their expression. Two proteins affect promoter recruitments of each other and collaborate in p21 expression. Moreover, sh-hTOP3α and sh-p53 in AGS cells caused a similar reduction in senescence and hTOP3α mRNA levels were lower in gastric and renal tumor samples. Conclusion: We concluded that hTOP3α interacts with p53, regulates p53 and p21 expression, and contributes to the p53-mediated tumor suppression. Clin Cancer Res; 20(6); 1489–501. ©2014 AACR.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Location Call Number Limitation Availability
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