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  • American Association for Cancer Research (AACR)  (4)
  • 1
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Research Vol. 72, No. 20 ( 2012-10-15), p. 5386-5395
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 20 ( 2012-10-15), p. 5386-5395
    Abstract: The mammalian Hippo signaling pathway has been implicated in oncogenesis in the context of solid tumors such as hepatocellular carcinoma. Mammalian sterile 20–like kinase 1 (MST1), the core component of the Hippo signaling pathway, is highly expressed in hematopoietic cells. However, its possible impact on tumorigenesis in this setting is unknown. In this study, we provide evidence that Mst1 loss in the mouse enhances chemically and genetically induced lymphoma development by inducing chromosomal instability. Mst1 deficiency increased susceptibility to T-cell acute lymphoblastic leukemia induced by mutagen exposure. Notably, before transformation Mst1−/− normal thymocytes showed no changes in proliferation or apoptosis in vitro and in vivo, but they displayed elevated levels of abnormal mitotic chromosomes and aneuploidy, conditions known to promote tumorigenesis. Mst1−/− mice also showed accelerated formation of spontaneous lymphomas in a p53-deficient background, accompanied by severe aneuploidy. In clinical specimens of lymphoma and leukemia, we documented frequent downregulation of MST1 expression, consistent with our findings. Taken together, our findings reveal a tumor suppressive function of Mst1 based on its ability to prevent chromosomal instability in lymphocytes. Cancer Res; 72(20); 5386–95. ©2012 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
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  • 2
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. P3-12-25-P3-12-25
    Abstract: Purpose:This study was performed to analyze the risk of second non-breast primary cancers (2nd_PrimaryCa) among Korean women who had received curative treatment for breast cancer. Methods:By using data from the Korean National Health Insurance Service Database between 2002 and 2017, we identified 399,621 women with invasive breast cancer. To analyze the long-term risk of 2nd_PrimaryCa, we included 52,506 women who underwent curative surgery between 2003 and 2008, and no history of cancers before the date of breast cancer surgery. The cumulative incidence of 2nd_PrimaryCa was estimated using the Kaplan-Meier analysis. Cox regression analysis was used to analyze the association between 2nd_PrimaryCa occurrence and factors including age, income level, receipt of systemic treatment or radiotherapy, family history of cancers, alcohol intake, and BRCA gene mutations.Results:A total of 3,084 (5.87%) patients developed 2nd_PrimaryCa. The 10-year incidence of 2nd_PrimaryCa was 5.78% (range, 5.56 – 6.00%). The median time to 2nd_PrimaryCa was 7.61 years (range, 6.22 – 9.31 years). Types of organs involved by 2nd_PrimaryCa were as followings: thyroid (18.84%), gynecological organs (12.78%), hepatobiliary structures (12.48%), thorax (11.25%), lower gastrointestinal (GI) tract (9.63%), upper GI tract (9.18%), skin (4.22%), lymphoma or leukemia (4.09%), brain (3.15%), head and neck (2.56%), and others (11.84%). The risk of 2nd_PrimaryCa was significantly associated with ≥ 60 years of age (hazard ratio (HR) = 2.15, 95% confidence interval (CI) = 1.60 – 2.90, p & lt; 0.01), Medical Aid recipients (HR = 8.79, 95% CI = 6.73 – 10.85, p & lt; 0.01), and receipt of chemotherapy and endocrine therapy (HR = 1.27, 95% CI = 1.12 – 1.43, p & lt; 0.01). Radiotherapy was related to lower incidence of 2nd_PrimaryCa (HR = 0.87, 95% CI = 0.81 – 0.94, p & lt; 0.01). Alcohol intake, family history of cancer, or carrying BRCA gene mutations was not related to the risk of 2nd_PrimaryCa. Among the patients with 2nd_PrimaryCa, the 5-year overall survival (OS) rate was 67.28% after the diagnosis of 2nd_PrimaryCa. Age of ≥ 60 years (HR = 1.67, 95% CI = 1.01 – 2.78, p = 0.04) and receiving chemotherapy and endocrine therapy (HR = 1.88, 95% CI = 1.43 – 2.46, p & lt; 0.01) were significantly related to inferior OS. Conclusions:The risk of 2nd_PrimaryCa was associated with personal and treatment factors in Korean patients with breast cancer. These factors are needed to be considered in the surveillance of breast cancer survivors. Citation Format: Haeyoung Kim, Su SSan Kim, Ji Sung Lee, Jae Sun Yoon, Hyuk Jai Shin, Jeong Eon Lee, Sei Kyung Lee, Il Yong Chung, So-Youn Jung, Young Jin Choi, Korean Breast Cancer Society. Risk of second primary cancers after curative treatment of breast cancer: A Korean nationwide 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 P3-12-25.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 3
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 13_Supplement ( 2017-07-01), p. 3385-3385
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 3385-3385
    Abstract: Pulmonary sclerosing hemangioma (PSH) is a benign tumor that usually presents as a solitary, well-defined mass in the lung. The PSH predominantly affects females with a higher incidence in the Far East. Histologically, the tumor cells in PSH consist of two cell types (cuboidal epithelial and polygonal stromal cells). Immunohistochemical and ultrastructural studies have identified that both cells are derived from undifferentiated respiratory epithelium that is the histologic origin of lung adenocarcinoma as well. Previous studies have shown that PSH and adenocarcinoma in the lung share some immunohistochemical and genetic features. However, as for somatic mutations, whereas many driver genes for lung adenocarcinomas have been identified, there have not been any candidate driver mutations identified in PSHs, except for low frequency mutations in β-catenin and TP53. Frequent somatic mutations identified in lung adenocarcinomas such as KRAS and EGFR have not been detected in PSH, suggesting that genomic alterations of these two lung tumors might be different from each other. Also, there is no evidence of PSH progression to lung cancers. These earlier data indicate that despite the common cellular origin of PSH and lung adenocarcinoma, genetic mechanisms for their development may be different. Based on the established concept that PSH is a true tumor, we hypothesize that it may harbor somatic mutations. In this study, we conducted whole exome sequencing of 44 PSHs and identified recurrent somatic mutations of AKT1 (43.2%) and β-catenin (4.5%). We used a second subset of 24 PSHs to confirm the high frequency of AKT1 mutations (overall 31/68, 45.6%; p.E17K, 33.8%) and recurrent β-catenin mutations (overall 3/68, 4.4%). Of the PSHs without AKT1 mutations, two exhibited AKT1 copy gain. AKT1 mutations existed in both epithelial and stromal cells. In two separate PSHs from one patient, we observed two different AKT1 mutations, indicating they were not disseminated but independent arising tumors. Since the AKT1 mutations were not found to co-occur with β-catenin mutations (or any other known driver alterations) in any of the PSHs studied, we speculate that this may be a single most common driver alteration to develop PSHs. Our study revealed genomic differences between PSHs and lung adenocarcinomas including a high rate of AKT1 mutation in PSHs. These genomic features of PSH discovered in the present study provide clues to understanding the biology of PSH and for differential genomic diagnosis of lung tumors. Citation Format: Seung-Hyun Jung, Min Sung Kim, Sun Shin, Mi-Ryung Han, Yu Jin Cho, So Youn Kim, Sug Hyung Lee, Yeun-Jun Chung. Genomic landscapes of pulmonary sclerosing hemangioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3385. doi:10.1158/1538-7445.AM2017-3385
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 4
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 1684-1684
    Abstract: Resistance to platinum-based chemotherapy is one of major causes of therapy failure and tumor recurrence in ovarian cancer patients. However, the molecular mechanism of platinum resistance is not fully understood. Here, we compared gene expression between cisplatin-sensitive and -resistant ovarian cancer cells using gene expression microarray analysis and found the significantly up-regulated expression of SERPINE1 encoding plasminogen activator inhibitor-1 (PAI-1), a serine protease regulating the fibrinolysis and extracelluar matrix, in cisplatin-resistant ovarian cancer cells. The correlation of high PAI-1 expression with low cisplatin sensitivity was confirmed in ovarian cancer cells. PAI-1 overexpression in ovarian cancer cells significantly decreased the sensitivity to cisplatin, whereas PAI-1 down-regulation by SERPINE1 siRNA or PAI-1 inhibitor increased cisplatin sensitivity. PAI-1 inhibited cisplatin-induced apoptosis in ovarian cancer cells by suppressing reactive oxygen species (ROS) production and DNA damage. PAI-1 also decreased cisplatin-induced ferroptosis through the upregulation of GPX4 levels. Furthermore, Kaplan-Meier survival analysis using TGGA data demonstrated that high PAI-1 expression was significantly associated with shorter platinum-free survival of patients with ovarian cancer. Collectively, these results illustrate that PAI-1 promotes cisplatin resistance in ovarian cancer cells by inhibiting ROS-mediated apoptosis and ferroptosis, suggesting that targeting PAI-1 increases the sensitivity to cisplatin in ovarian cancer. Citation Format: Mi Jeong Kwon, Ha Yeong Chae, So Young Lee, Shin Ung Kang, Tae Woong Jung, Soo Youn Cho, Jinil Han, Hyojin Jeong, Chang Ohk Sung, Young Kee Shin. Plasminogen activator inhibitor-1 (PAI-1) promotes cisplatin resistance in ovarian cancer cells by inhibiting ROS-mediated apoptosis and ferroptosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1684.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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