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  • American Association for Cancer Research (AACR)  (6)
  • English  (6)
  • 2020-2024  (6)
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  • American Association for Cancer Research (AACR)  (6)
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  • English  (6)
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  • 2020-2024  (6)
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  • 1
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 7_Supplement ( 2023-04-04), p. 376-376
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 376-376
    Abstract: As part of our previous studies on the anti-tumor mechanisms of sorafenib, one of the primary treatments for advanced hepatocellular carcinoma (HCC), we found that suppression of cyclin E1 in HCC cells correlates with sensitivity to sorafenib (Chiun Hsu et al. Clin Cancer Res. 2016:2555). Furthermore, the combination of sorafenib and a cyclin-dependent kinase inhibitor was found to have synergistic anti-tumor effects. Specifically, we found that inhibiting DKK1 (dickkopf1), an essential regulator of Wnt signaling, had a synergistic effect. In sorafenib-sensitive HCC cells, DKK1 mRNA and protein expressions were suppressed following treatment with sorafenib, but not in sorafenib-resistant cells. HCC cells resistant to sorafenib were induced to apoptosis with knockdown of DKK1 expression. The apoptosis-inducing effects of sorafenib were enhanced by DKK1 inhibitors, and beta-catenin suppression was found to be crucial to this effect. In addition, mouse tumors secrete DKK1 into the blood and its presence correlates positively with tumor size and survival during sorafenib treatment. Suppression of DKK1 in hepatocellular carcinoma cells may serve as a pharmacodynamic biomarker for predicting sorafenib or CDK inhibitor efficacy. Sorafenib combined with a DKK1 inhibitor may improve sorafenib's efficacy in hepatocellular carcinoma. (Supported by MOST 106-2314-B-002-229-MY3, MOST 109-2634-F-002-043, MOST 109-2314-B-002-229 -MY3, MOST 110-2634-F-002-044 from Ministry of Science and Technology, Taiwan) Citation Format: Lin Li, Chia-Lang Hsu, Liang-In Lin, Bin-Shyun Lee, Ping-Yun Ou, Ann-Lii Cheng, Chiun Hsu, Da-Liang Ou. DKK1 inhibition can overcome sorafenib resistance in hepatocellular carcinoma cells through beta-catenin suppression [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 376.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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  • 2
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 7_Supplement ( 2023-04-04), p. 1355-1355
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 1355-1355
    Abstract: Background: Previous studies have revealed esophageal dysplasia, a precancerous lesion of ESCC, harbors similar mutations and markers of genomic instability as ESCC does. This observation suggests that other factors such as evasion of immune surveillance may be involved in the progression of esophageal dysplasia to ESCC. The study aimed to identify the key differences in the immune TME between esophageal dysplasia and ESCC. Methods: Patients with a history of diagnosing with esophageal dysplasia for at least two times prior to the diagnosis of ESCC were enrolled. Formalin-fixed paraffin-embedded tissues from esophageal dysplasia diagnosed more than 6 months prior to the diagnosis of ESCC (denoted as dysplasia-1), esophageal dysplasia diagnosed within 6 months prior to the diagnosis of ESCC (denoted as dysplasia-2), and ESCC were retrieved. Transcriptomic data of esophageal dysplasia and ESCC tissues were generated by NanoString nCounter platform with Human PanCancer Immune Profiling panel, and were further analyzed for the expression levels of infiltrating immune cells by CIBERSORT. Results Six ESCC patients (M:F= 6:0), with median age of 56.6 (range: 43.3-79.1) years, were enrolled. The median time between the diagnosis of dysplasia-1 and that of ESCC was 10.2 months (range 6.0-38.6) and the median time between the diagnosis of dysplasia-2 and that of ESCC was 2.3 months (range 0.0-6.0). The analysis of immune cell signatures defined by NanoString platform revealed that multiple cell types were significantly increased in ESCC compared with dysplasia-1 (mast cell, macrophage, CD8 T cell, B cell and dendritic cell, all P & lt; 0.05) and in ESCC compared with dysplasia-2 (macrophage, mast cell, dendritic cell, B cell, T cell, CD4 T cell, regulatory T cell, cytotoxic T cell, NK CD56dim cell, and T helper cell, all P & lt; 0.05). There was no significant difference in the immune cell signatures between dysplasia-1 and dysplasia-2. Immune cells classified by CIBERSORT showed an increase of M2 macrophage and a decrease of M1/M2 ratio in ESCC compared with dysplasia-1 or dysplasia-2 (both P & lt; 0.05). Conclusions: Our data, showing an increase of M2 macrophage in TME of ESCC compared with its precancerous esophageal dysplasia, suggest that evolution of immune TME may play a role in the progression of esophageal dysplasia to ESCC. (Funded by MOST 108-2314-B-002-076-MY3, MOST 109-2314-B-002-231-, MOHW 111-TDU-B-221-114006, NTUCCS-110-10, and NTUCCS-111-05) Citation Format: Jhe-Cyuan Guo, Chia-Lang Hsu, Yen-Lin Huang, Tsung-Che Wu, Chih-Hung Hsu. Evolution of immune tumor microenvironment (TME) from esophageal dysplasia to esophageal squamous cell carcinoma (ESCC) [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 1355.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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  • 3
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 31, No. 5 ( 2022-05-04), p. 1111-1118
    Abstract: To investigate the standardized incidence ratios (SIR) of stroke in patients with head and neck cancer and their relationship to radiotherapy. Methods: Patients with head and neck cancer ages 20–85 years were enrolled from 2007 to 2016 using the Taiwan Cancer Registry. The study endpoint was fatal and non-fatal ischemic stroke, ascertained by the National Health Insurance Research Database. Age- and sex-adjusted SIRs, categorized by 10-year age standardization, were used to compare the patients with head and neck cancer with a randomly selected 2,000,000 general population. We compared the risk of stroke in patients with head and neck cancer who received radiotherapy or surgery alone. Multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CI) were obtained from Cox regression analysis with competing risk. Results: Among 41,266 patients (mean age, 54.1 years; men, 90.6%) in the median follow-up period of 3.9 years, 1,407 strokes occurred. Compared with the general population, the overall SIR of stroke was 1.37 (95% CI, 1.30–1.44) in patients with head and neck cancer. In patients with head and neck cancer, the fully adjusted HR of stroke in those who received radiotherapy was 0.96 (95% CI, 0.83–1.10), compared with those who received surgery alone. Conclusions: Patients with head and neck cancer had a higher risk of fatal or non-fatal ischemic stroke. The risk of stroke was not higher in patients initially treated with radiotherapy. Impact: Oncologists should emphasize stroke prevention in all patients with head and neck cancer, not only in those who received radiotherapy.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 4
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. 1590-1590
    Abstract: Background: Immunotherapy targeting co-stimulatory receptors of T cells is under active clinical investigation. Inducible co-stimulator (ICOS) is an important co-stimulatory receptor on effector T cells (Teffs) that also promotes tumor growth due to its high expression on regulatory T cells (Tregs). Human IgG1 anti-ICOS therapeutic antibodies may therefore induce antitumor immunity by stimulating ICOSLow Teffs and depleting ICOSHigh Tregs. This study explored the clinical significance of ICOS expression and Treg content in hepatocellular carcinoma (HCC). Patients and Methods: We collected tumor tissues from HCC patients who received curative hepatectomy at the National Taiwan University Hospital, Taipei, Taiwan. Dual immunohistochemistry (IHC) was performed to evaluate the expression of ICOS and Foxp3. The cell density and distances between single- and dual-expressing cells in the tumor center, margin, and the peritumor area were quantitated by digital pathology. Associations between clinical outcome or clinical metadata and ICOS/Foxp3 expression were analyzed. Results: A total of 142 patients (male: female= 112: 30, median age of 61.0 years) were enrolled. Among them, 87 (61.3%) had chronic hepatitis B virus (HBV) infection, 33 (23.2%) had chronic hepatitis C (HCV) infection, and 22 (15.5%) had no HBV/HCV infection. In this cohort, low AFP level ( & lt; 20 ng/ml) and early stage, but not age, gender, or viral etiology, were significantly associated with improved overall survival (OS). However, the density of ICOS+Foxp3+ cells and the ratio of ICOS+Foxp3+/total Foxp3+ cells were significantly higher (p & lt;0.001) in the tumor center than in the peritumor area especially in viral-related HCC. Similarly, patients with a high ratio of ICOS+Foxp3+/total Foxp3+ cells (p=0.074) or with high ICOS expression (p & lt;0.05) in the tumor center were associated with a shorter OS. Finally, a shorter distance between ICOS+Foxp3+ cells and ICOS+Foxp3- cells in the tumor center was significantly associated with a shorter OS (p & lt;0.05) suggesting active immunosuppression of ICOS+ Tregs on ICOS+ Teff cells. Conclusions: A high proportion of Tregs in HCC tumors expresses ICOS, implying a strong immunosuppressive environment. Importantly, high ICOS expression in HCC tumors, a high ratio of ICOS+Foxp3+/total Foxp3+ cells and a shorter distance between ICOS+ Tregs and other ICOS+ cells are all associated with a poor OS, suggesting that targeting ICOS in this indication may provide clinical benefit (This work is partly supported by MOST 108-2314-B-002-073). Citation Format: Li-Chun Lu, Cecilia Deantonio, Laura Mitchell, Yi-Hsuan Lee, Yu-Yun Shao, Ron Chen, Marianne Cowan, Matthew Corser, Lorcan Sherry, Ann-Lii Cheng, Chia-Chi Lin, Sonia Quaratino, Richard C. Sainson, Chih-Hung Hsu. High ICOS/FOXP3 Tregs content in the tumor microenvironment is associated with poorer survival in patients with hepatocellular carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1590.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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  • 5
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 12_Supplement ( 2022-06-15), p. 6386-6386
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 6386-6386
    Abstract: Pancreatic ductal adenocarcinoma (PDAC) is a common malignancy that shows high cancer-mortality and poor prognosis, in the absence of obvious symptoms and biomarkers for early diagnosis. Gemcitabine is a type of chemotherapy drug which commonly used to treat PDAC, however, the rapid acquisition of resistance to gemcitabine treatment has been observed in many of PDAC patients. The miRNA-producing enzymes Dicer is crucial for the maturation of miRNAs, and we found previously that ERK/Sp1 signaling transactivate both gene and protein expressions of Dicer, leading an acquisition of gemcitabine resistance in pancreatic cancer cells both in vitro and in vivo. In this study, we further identified that phosphomimetic S1016E of Dicer may regulate miRNAs maturation, resulting an imbalance of glutaminase (GLS) and glutamine synthetase (GS/GLUL). Metabolism analysis revealed that gemcitabine-resistant PANC-1 (PANC-1/GEM) cells have high glutamine dependence and GLS/GLUL ratio. Our study suggests that phosphomimetic Dicer S1016E plays a critical role in glutamine metabolism reprogramming and gemcitabine resistance of pancreatic cancer. Citation Format: Ching-Feng Chiu, Ji Min Park, Yu-Shiuan Shen, Chia-Ying Lin, Tung-Wei Hsu, Yen-Hao Su, Hsin-An Chen. Phosphomimetic Dicer rewires glutamine metabolism and gemcitabine resistance in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6386.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 6
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 7_Supplement ( 2023-04-04), p. 2211-2211
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 2211-2211
    Abstract: Introduction: The presence of TLS in tumors is associated with improved efficacy of immunotherapy in various types of cancer. The significance of TLS in patients with ESCC has been sporadically reported. The study aimed to investigate the prognostic significance of TLS in patients with locally advanced ESCC receiving neoadjuvant chemoradiotherapy (CRT). Patients and Methods: We included two cohorts of locally advanced ESCC patients from two referral centers of Taiwan. Cohort A consisted of 99 patients treated with paclitaxel/cisplatin-based CRT, 69 of them being neoadjuvant CRT and 30 of them being definitive CRT, between 2002 and 2015; cohort B consisted of 67 patients treated with paclitaxel/carboplatin-based neoadjuvant CRT between 2012 and 2018. Primary tumor tissues were retrospectively collected for immunohistochemical stains by CD20 (clone L26; Zytomed, Berlin, Germany) and CD23 (clone DAK-CD23; agilent Dako, California, U.S.A.). TLS was defined as aggregation of CD20 B cells, and mature TLS was defined as TLS with CD23-positively stained germinal center. Patients’ characteristics were compared between those with or without TLS or mature TLS. The impact of TLS or mature TLS on patients’ overall survival (OS) was analyzed by Kaplan-Meier method and log rank test. Results: In cohort A (median age of 56 years, M:F= 88:11), no TLS, immature TLS, and mature TLS were seen in 52, 35, and 12 patients, respectively. In cohort B (median age of 55 years, M:F= 64:3), no TLS, immature TLS, and mature TLS were seen in 27, 25, and 15, respectively. In cohort A, the presence of TLS is more commonly seen in ESCC with the primary site at upper (58%) and lower segments (63%) than middle segment of esophagus (35%) (p=0.039), and the mature TLS is more commonly seen at lower segment (25%) than other segments (8%) (p=0.033). The pathological complete response (pCR) was not significant different between patients with vs without TLS in cohort A (39% vs 43 %, p= 0.75), but trended to be lower in patients with TLS than without in cohort B (28% vs 52 %, p= 0.061). Besides, pCR rate trended to be lower in patients with mature TLS than without in both cohorts (13% vs 45 %, p= 0.080, for cohort A; 28% vs 43 %, p= 0.23, for cohort B). As patients with or without TLS did not differ in their OS in both cohorts, patients with mature TLS trended to have worse overall survival in both cohort A (HR: 1.4 [95% CI 0.33-3.05], p=0.29) and cohort B (HR: 1.6 [95% CI 0.81-2.98] , p=0.15). Conclusion: In two independent cohorts of locally advanced ESCC patients receiving paclitaxel/platinum-based CRT, we did not find the correlation of the presence of TLS or mature TLS in pre-treatment primary ESCC tumor tissue with the favorable treatment outcomes. (The study was supported by the grant NTUH 110-S5021, the grant MOST 108-2314-B-002-076-MY3, and grant MOHW 111-TDU-B-221-114006) Citation Format: Ta-Chen Huang, Cher-Wei Liang, Yu-I Li, Jhe-Cyuan Guo, Chia-Chi Lin, Jang-Ming Lee, Yin-Kai Chao, Chih-Hung Hsu. The prognostic role of tertiary lymphoid structure (TLS) in locally advanced esophageal squamous cell carcinoma (ESCC) [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 2211.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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