Artykuły w czasopismach na temat „Guo min hui yi”

This study investigates the power dynamics in Fang Si-Chi's First Love Paradise, a work by the late Taiwanese author Lin Yi-Han, using the Foucauldian Discourse Analysis method. Specifically, it focuses on the linguistic interactions between the main characters to uncover the power structures at play. The analysis reveals that Li Guo-Hua's manipulation of language, within the context of classic Chinese literature, plays a pivotal role in establishing and perpetuating his power. Throughout the narrative, Li Guo-Hua subjects Fang Si-Chi to prolonged sexual and psychological abuse, thereby creating a power dynamic characteristic of Foucauldian discourse. He positions himself as her teacher, exerting control through the distortion of truthful knowledge, linguistic manipulation, and the denial of Fang's agency. This research sheds light on how power can be intricately woven into language and discourse, enabling the exploitation of individuals within intimate relationships. The findings underscore the importance of critically examining linguistic power dynamics in literary works, as they reflect broader societal constructs and behaviors.

Abstract Cancer cells reprogram their glucose metabolism from oxidative phosphorylation to aerobic glycolysis. This metabolic transformation is partly based on the activity alterations of a rate limiting enzyme known as the pyruvate kinase M2 (PKM2), which is responsible for the conversion of phosphoenolpyruvate (PEP) into pyruvate. Attributed to its critical regulatory role. PKM2 is recognized as the pivotal enzyme in cancer glucose metabolism By reducing the enzyme activity of PKM2, cancer cells attain a greater fraction of glycolytic metabolites for macromolecule synthesis needed for rapid proliferation. Hydrogen sulfide (H2S), an endogenously produced gasotransmitter that acts as a critical mediator in multiple physiological processes, modifies proteins mainly through the persulfide (-SSH) bond formation, which is called sulfhydration. Our preliminary study demonstrates that H2S stimulates PKM2 sulfhydration at multiple cysteine residues, including cysteine 326, leading to the destabilization of active tetrameric PKM2 form into dimers or monomers. The PKM2 dimer/monomer further translocates into the nucleus to simulate the activation of glycolytic related genes. Blocking PKM2 sulfhydration at cysteine 326 through amino acid mutation stabilizes PKM2 tetramer and crystal structure further indicates that the tetramer organization of PKM2C326S is different from the currently known T or R states, revealing PKM2C326S as a newly identified intermediate form. Blocking PKM2 sulfhydration at cysteine 326 inhibited cell proliferation and tumor growth in xenograft mouse model. In summary, our current study illustrates that H2S-mediated sulfhydration induces the dissociation of the PKM2 tetramer, resulting in the reduced PKM2 activity and subsequently inhibits breast cancer cell proliferation and tumor growth. Targeting the sulfhydration site of PKM2 emerges as a promising therapeutic target specific for cancer metabolism. Citation Format: Po-Chen Chien, Rong-Hsuan Wang, Pin-Ru Chen, Yue-Ting Chen, Yi-Chang Chen, Yu-Hsin Chu, Chia-Chen Chien, Shao-Yun Lo, Zhong-Liang Wang, Min-Chen Tsou, Ssu-Yu Chen, Guang-Shen Chiu, Wen-Ling Chen, Yi-Hsuan Wu, Hui-Ching Wang, Shu-Yi Lin, Wen-Ching Wang, Hsing-Jien Kung, Lu-Hai Wang, Hui-Chun Cheng, Kai-Ti Lin. Hydrogen sulfide switches the glucose metabolism through sulfhydration on pyruvate kinase M2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 437.

Abstract Background: Morpho-physiological alternations of platelets provided a rationale to harness RNA sequencing of tumor-educated platelets (TEPs) for preoperative diagnosis of cancer. Timely, accurate, and non-invasive detection of ovarian cancer in women with adnexal masses presents a significant clinical challenge. Patients and Methods: This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n=3; Netherlands, n=5; Poland, n=1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. Results: The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. Analysis of public datasets suggested that TEPs had potential to detect multiple malignancies (Table 1). Conclusions: TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, early-stage ovarian cancer as well as other malignancies. However, these observations warrant prospective validations in a larger population before clinical utilities. Table 1. Performance for TEPs in public pan-cancer datasets. Disease n Healthy Control AUC, area under the curve (95% CI) Women NSCLC (non-small-cell lung cancer) 126 77 0.758 (0.691-0.825) Breast cancer 38 77 0.817 (0.726-0.909) Colorectal cancer 18 77 0.973 (0.945-1.000) Pancreatic cancer 16 77 0.993 (0.981-1.000) Glioblastoma 10 77 0.923 (0.831-1.000) Men NSCLC 119 82 0.746 (0.677-0.815) Colorectal cancer 25 82 0.933 (0.884-0.982) Pancreatic cancer 22 82 0.993 (0.984-1.000) Glioblastoma 19 82 0.981 (0.959-1.000) All NSCLC 245 159 0.774 (0.728-0.820) Colorectal cancer 40 159 0.978 (0.961-0.996) Breast cancer 38 159 0.821 (0.736-0.906) Pancreatic cancer 35 159 0.987 (0.974-0.999) Glioblastoma 35 159 0.931 (0.890-0.972) Hepatobiliary carcinomas 14 159 0.991 (0.978-1.000) Citation Format: Yue Gao, Chun-Jie Liu, Hua-Yi Li, Xiao-Ming Xiong, Sjors G.j.g. In ‘t Veld, Gui-Ling Li, Jia-Hao Liu, Guang-Yao Cai, Gui-Yan Xie, Shao-Qing Zeng, Yuan Wu, Jian-Hua Chi, Qiong Zhang, Xiao-Fei Jiao, Lin-Li Shi, Wan-Rong Lu, Wei-Guo Lv, Xing-Sheng Yang, Jurgen M.j. Piek, Cornelis D de Kroon, C.a.r. Lok, Anna Supernat, Sylwia Łapińska-Szumczyk, Anna Łojkowska, Anna J. Żaczek, Jacek Jassem, Bakhos A. Tannous, Nik Sol, Edward Post, Myron G. Best, Bei-Hua Kong, Xing Xie, Ding Ma, Thomas Wurdinger, An-Yuan Guo, Qing-Lei Gao. Platelet RNA signature enables early and accurate detection of ovarian cancer: An intercontinental, biomarker identification study [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 LB168.

Abstract Background: CHASE001 (NCT05544123), a prospective, non-interventional multicenter study exploring real-world treatment and referral behavior of Chinese county patients (pts) with HER2+ or HR+/HER2– breast cancer is ongoing since September 2022. A prespecified interim analysis (IA) on 750 HER2+ and HR+/HER2- early breast cancer (eBC) was reported at the ESMO Congress 2023. In the 2nd IA from CHASE001, adjuvant treatment selection for patients with HR+/HER2- eBC will be evaluated. Methods: The study was designed to enroll 2500 pts, including four cohorts (HER2+ eBC, HR+/HER2-eBC, HER2+ advanced BC, and HR+/HER2- aBC). In this IA, HR+/HER2- eBC pts after surgery were included. Descriptive statistics reported patient demographics, clinical and disease characteristics and treatment patterns. To investigate the factors associated with chemotherapy-free regimen, non-anthracycline chemotherapy regimen and ovarian function suppression (OFS), univariate and multivariate logistic regression analyses were conducted. Results: At data cutoff (May 17, 2023), 697 HR+/HER2- eBC pts (median age 52 years, 45.77% pT2, 50.93% pN0, 56.10% G2) were included from 26 institutions in China county areas, 338 (48.49%) were premenopausal. 584 (83.79%) received adjuvant chemotherapy, with a few (47/584, 8.05%) initially developing their treatment plan at a higher level hospital (national or provincial tertiary hospital). AC-T (309/584, 52.91%) was the most commonly used regimen. 181 (30.99%) pts received non-anthracycline chemotherapy regimen (mainly TC), and pts with N0, age≥65 years and ki67 < 20% had the strongest association to this regimen (multivariate OR=0.082, 95%CI [0.037,0.179], OR=0.463, 95%CI [0.250,0.859], and OR=0.642, 95%CI [0.418,0.985], respectively). Interestingly, on univariate analysis pts initially diagnosed in a higher level hospital were significantly associated with non-anthracycline regimen (P=0.0109), however on multivariate analysis it was no longer significant. 483 pts received endocrine therapy, including 234 (48.45%) premenopausal pts. The most commonly used endocrine regimen for premenopausal pts was OFS/OFS+ (122/234, 52.14%) ,of which half (61, 50%) were prescribed OFS+TAM/TOR; followed by TAM/TOR monotherapy (69/234, 29.49%). The proportions of patients classified as low, intermediate, and high clinical risk for recurrence (investigator assessed)were 33.62%, 42.67% and 23.71%. The OFS rate were 39.74% in low, 61.62% in intermediate and 70.91% in high risk pts, respectively. Multivariable analyses found that high clinical risk, age < 45 years and ki67 < 20% were strongly associated with the use of OFS (OR=0.210, 95%CI [0.066,0.674], OR=0.327, 95%CI [0.165,0.649], and OR=0.405, 95%CI [0.194,0.845], respectively). For postmenopausal pts, AI monotherapy (84.74%) was the most commonly used endocrine regimen. Conclusions: To our knowledge, this is the first real-world study evaluating the treatment patterns and referral behavior of BC pts in China counties. The 2nd IA results presented showed the current systemic adjuvant treatment preferences and influence factors from a large sample of HR+/HER2- eBC pts in China counties, which were generally consistent with China BC treatment guidelines. Table 1. Utilization of adjuvant systemic therapy regimens in 697 HR+/HER2− eBC pts, China counties AC-T: (dd)doxorubicin/epirubicin, cyclophosphamide, followed by (dd)paclitaxel/docetaxel; TC: paclitaxel/docetaxel, cyclophosphamide; AC: doxorubicin/epirubicin, cyclophosphamide; TAC: docetaxel, doxorubicin/epirubicin, cyclophosphamide; TAM: tamoxifen; OFS: ovarian function suppression; AI: aromatase inhibitors; TOR: toremifene; CDK4/6i: cyclin-dependent kinase 4/6 inhibitors; “Other” category includes various therapies used in <1% of patients each Citation Format: Yinghua Ji, Honglan Qu, Feidu Zhou, Juan Wang, Qianfu Wu, Guohua Dai, Mengyou Liu, Wenbo He, Wei Liang, Qiuli Meng, Yun Ren, Guoxiang Luo, Hongjian Wang, Hui Liu, Zien Qin, Yingguo Tian, Huali Tang, Hongmei Liu, Jun Luo, Zengfeng Yu, Guinv Hu, Jianzhi Gao, Xiang Tan, Yi Liu, Yuanjiang Zhang, Ming Wang, Min Zhang, Ping Lu. Adjuvant Treatment Selection for County-Level Patients with HR+/HER2- Early Breast Cancer in a Real-Life Setting in China [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-16-08.

Chen, Qiu-Hong, Ri-Li Ge, Xiao-Zhen Wang, Hui-Xin Chen, Tian-Yi Wu, Toshio Kobayashi, and Kazuhiko Yoshimura. Exercise performance of Tibetan and Han adolescents at altitudes of 3,417 and 4,300 m. J. Appl. Physiol. 83(2): 661–667, 1997.—The difference was studied between O2 transport in lifelong Tibetan adolescents and in newcomer Han adolescents acclimatized to high altitude. We measured minute ventilation, maximal O2 uptake, maximal cardiac output, and arterial O2 saturation during maximal exercise, using the incremental exercise technique, at altitudes of 3,417 and 4,300 m. The groups were well matched for age, height, and nutritional status. The Tibetans had been living at the altitudes for a longer period than the Hans (14.5 ± 0.2 vs. 7.8 ± 0.8 yr at 3,417 m, P < 0.01; and 14.7 ± 0.3 vs. 5.3 ± 0.7 yr at 4,300 m, P < 0.01, respectively). At rest, Tibetans had significantly greater vital capacity and maximal voluntary ventilation than the Hans at both altitudes. At maximal exercise, Tibetans compared with Hans had higher maximal O2 uptake (42.2 ± 1.7 vs. 36.7 ± 1.2 ml ⋅ min−1 ⋅ kg−1at 3,417 m, P < 0.01; and 36.8 ± 1.9 vs. 30.0 ± 1.4 ml ⋅ min−1 ⋅ kg−1at 4,300 m, P < 0.01, respectively) and greater maximal cardiac output (12.8 ± 0.3 vs. 11.4 ± 0.2 l/min at 3,417 m, P < 0.01; 11.5 ± 0.5 vs. 10.0 ± 0.5 l/min at 4,300 m, P < 0.05, respectively). Although the differences in arterial O2saturation between Tibetans and Hans were not significant at rest and during mild exercise, the differences became greater with increases in exercise workload at both altitudes. We concluded that exposure to high altitude from birth to adolescence resulted in an efficient O2 transport and a greater aerobic exercise performance that may reflect a successful adaptation to life at high altitude.

Abstract Collective cell migration has been demonstrated the importance in cancer metastasis. Instead of single cell migration, collective cell migration requires E-cadherin for the cohort cell migration. Rab11 the recycling vesicle protein plays the key role in E-cadherin dynamics and mediates collective cell migration. In this study, Src was hypothesized to regulate Rab11 mediated collective cell migration. Our results demonstrated Src inhibitor Dasatinib has less toxicity in HT-29 colon cancer cells, instead, the cell morphology was turned aggregated. The immunofluorescence image also showed E-cadherin polarity was lost after Dasatinib treatment and increased the potential of cell-cell contact inhibition. In transwell assay, Rab11 was found colocalized with E-cadherin in collective migrated cells. Dasatinib treatment can suppress collective cell migration and decrease the interaction of Rab11 and E-cadherin. This study demonstrated the important role of Src in Rab11 mediated collective cell migration through E-cadherin dynamics in colon cancer. Citation Format: Yi-Wen Lu, Xiang-Ling Hou, Hui Min Koo, Wei-Ting Chao. Src inhibitor suppresses rab11 mediated collective cell migration in colon cancer cells [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 5819.

Abstract B7-H3 (CD276) is a type I transmembrane protein belonging to the B7 family of immune-regulatory ligands. Initially reported as a costimulatory signal of human T cells, increasing evidence suggests that it may also have coinhibitory function. TLT-2 has been identified as a potential cognate receptor for B7-H3, but others may exist. Overexpression of B7-H3 protein is found in a variety of human cancers, including lung adenocarcinomas, neuroblastomas, gliomas, and pancreatic tumors—and is associated with poor prognosis and survival. While B7-H3 can promote T cell activation and anti-tumor responses in the context of CD3 stimulation, its coinhibitory function inhibits T and NK cell activity in the tumor microenvironment. We generated 6B5, a fully human B7-H3 monoclonal antibody, from murine B7-H3 knock-out RenMab™ mice, which contain the full human immunoglobulin variable domain. 6B5 is cross-reactive with rodent and cynomolgus monkey B7-H3. It displays higher affinity for tumor cell lines than Enoblituzumab. 6B5 has no staining on normal human tissues. In vitro antibody-dependent cellular cytotoxicity (ADCC) against H520 squamous cell carcinoma cells was potentiated by 6B5 relative to Enoblituzumab and, critically, did not exhibit the hook effect at high dosage. In vivo efficacy of 6B5 in humanized B7-H3 mice bearing murine EL4 lymphomas was comparable to Enoblituzumab. ADCC enhancement in vivo was comparable to afucosylation or five-point mutations. Epitope mapping revealed non-overlapping B7-H3 binding epitopes of 6B5 and Enoblituzumab. Taken together, these data suggest that 6B5 is a promising therapeutic anti-human B7-H3 IgG monoclonal antibody that may find clinical application in a range of cancers, including current refractory types. Citation Format: Yunyun Chen, Jiangmei Li, Yanan Guo, Wenqi Hu, Ting Mao, Li Hui, W. Frank An, Yi Yang, Feng Li. 6B5, an anti-human B7-H3 therapeutic antibody that enhances antibody-dependent cellular cytotoxicity and inhibits tumor growth in B7-H3-humanized mice [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 1528.

Abstract Cells release molecules through vesicles or into specific locations through exocytosis. Extracellular vesicle is divided into ectosomes and exosomes. Exosomes has been the main mechanism of discussion in recent studies and cancer research. As Exosomes with a diameter of ~30-160 nm (with an average diameter of 100 nm) carries intracellular molecules such as DNA, RNA, miRNA, proteins, and lipids. The physiological function of exosomes is not fully understood at present, it is important to understand the role of exosome in cancer. Src is highly activated in colon cancer and Src inhibition is the potential treatment strategy in colon cancer. In this study, colon cancer cells HT-29 were used to investigate the difference sizes of exosomes that response to Src inhibitor treatment. In the preliminary results, the exosome from HT-29 cultured medium were isolated and examined by transmission electron microscopy (TEM). The micrograph showed the average size of exosome is around 100 nm. When HT-29 were treated with Dasatinib (DST) the Src inhibitor, the drug resistant (DSTR) cells were grown, the secreted exosome from DSTR were collected and demonstrated the bigger size of exosome with average diameter of 130 nm. The role of the size changes of exosome in response to Dasatinib resistant will be further investigated, however, this study provides the clues that exosome detection can be applied in monitoring drug resistance. Citation Format: Hui Min Koo, Yi-Wen Lu, Yu-Chi Tseng, Kai-Yu Tseng, Yen-Tse Lu, Wei-Ting Chao. Visualizing exosome structure in Dasatinib resistant colon cancer cells [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 2365.

Abstract Cell adherens junction plays an important role in cell communication and regulation. E-cadherin is an important protein as adherens junctions. Loss of E-cadherin leads to epithelial cells transit to mesenchymal cells. Studies has demonstrated that E-cadherin dominates cell contact inhibition, which plays an important role in cell growth, however, recent studies demonstrated collective cell migration required E-cadherin expression escaping cell growth inhibition is important in metastasis. E-cadherin dynamics has been shown to be regulated by vesicle trafficking, however, the detail mechanism of vesicle trafficking in collective cell migration is not clear. This study is investigating the relationship between the endocytosis mechanism of E-cadherin and its dynamic expression resulting in collective cell migration. The expression of E-cadherin was controlled by regulating the concentration of calcium and EDTA to observe its effect on cell-cell contact. Through Transmission electron microscope, immunofluorescence staining and western blotting to observe the relationship between vesicle trafficking and E-cadherin. Collective cell migration is analyzed by transwell assay. When calcium concentration was increased, the E-cadherin in cell-cell contacts became stronger. Conversely, when EDTA concentration was increased, the E-cadherin in the cell-cell contacts became weaker. Meanwhile, we found colocalization occurs in Rab5 and Rab11 with E-cadherin. Besides, intracellular E-cadherin transported to the lysosome for degradation was also observed. We identified the role of E-cadherin is regulated in endocytosis mechanism and at cell-cell contacts through different regulatory, which provides a basis for the future use of drugs to affect E-cadherin expression to inhibit collective cell migration. Citation Format: Hui Min Koo, Xiang-Ling Hou, Yu-Lin Li, Yi-Wen Lu, Viriya Adhiguna Winarso, Yu-Cheng Weng, Wei-Ting Chao. Investigates the role of vesicle trafficking in E-cadherin dynamics in collective migrated colon cancer cells [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 1001.

Abstract Collective cell migration is one of the most important cellular events where a cluster of cells moves together in a coordinated way. Many studies have found this phenomenon as the hallmark of cancer progression and metastasis. In epithelial single cell migration, downregulation of adherens junction (AJ) molecule E-cadherin occurs at the initial step known as the Epithelial to Mesenchymal Transition (EMT). However, in collective cell migration, E-cadherin junction is maintained to provide adhesion between cells. Moreover, it also mediates the cell-cell intercommunication that is critical, for instance, to alter the group polarization through actin cytoskeleton remodeling. Interestingly, Epidermal Growth Factor Receptor (EGFR) was found to colocalize with E-cadherin in the cell-cell contact region, implicating that E-cadherin and EGFR might interact in the cell junction of collective cell migration. To address this, a human colorectal cancer cell line exhibiting epithelial phenotype HT-29 was used. The cell density and calcium presence were modified to infer the effect of differential expression and stability of E-cadherin on the cellular signaling of proliferation and migration. The results showed that stable and enhanced expression of E-cadherin downregulates EGFR expression and reduces its activity. Moreover, the Src phosphorylation increased when the cell-cell contact was strengthened via calcium addition and decreased when the cell-cell contact was diminished via calcium chelation. Overall, this indicates that E-cadherin expression at the cell-cell junction and contact stability determine the EGFR expression, activity, and Src phosphorylation. With the goal of deciphering the relationship of E-cadherin and EGFR in cell contact, proliferation, and migration, we intend to finally implement the knowledge as a strategy or approach in promoting alternative methods to inhibit metastasis. Citation Format: Viriya Adhiguna Winarso, Yi-Wen Lu, Yu-Cheng Weng, Xiang-Ling Hou, Hui Min Koo, Yu-n Li, Wei-Ting Chao. Interaction of E-cadherin and EGFR in the collective cell migration of colon cancer cells [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 1578.

Abstract Collective cell migration is the cell cohort migrates toward the direction. Other than single cell migration, collective cell migration requires cell-cell connection with E-cadherin, however, E-cadherin is the epithelial marker in epithelial mesenchymal transition and acts as tumor suppressor function. Therefore, the role of E-cadherin in collective cell migration is still under investigated. In the collected cells, cell migration and cell division are coordinated for the cohort motility, the mechanism is still not clear. This study is to investigate the role of E-cadherin orientation in cell division dependent collective cell migration. Colorectal cancer cell line HT29 with epithelial morphology were used and treated with Cetuximab and Dasatinib to inhibit EGFR and Src activity. Cells were also incubated on fibronectin to monitor the matrix dependent environment. The polarity of E-cadherin distribution and cell contact inhibition were defined and detected by Immunofluorescence. The molecular expression of p-FAK, CDK4, and cell proliferation marker, Ki67 were revealed by Immunofluorescence confocal microscopy and Western blot. The collective cell migration is analyzed and compared by wound healing and transwell assay. In the results, the polarized distribution of E-cadherin in leading cells which revealed pFAK expression on the cell membrane was associated with Ki67 and CDK4 positive proliferated cells. When cells were grown on fibronectin, the proliferated cells in the leading were decreased. When cells were treated with cetuximab, the E-cadherin distribution were not changed and had fewer effect on cell migration. However, dasatinib treatment can modulate E-cadherin orientation and suppress cell proliferation and cell migration. These results suggested modulate E-cadherin orientation such as Src inhibition can be the potential treatment strategy in colon cancer Citation Format: Yu-Lin Li, Yu-Cheng Weng, Viriya Adhiguna Winarso, Yi-Wen Lu, Hui Min Koo, Xiang-Ling Hou, Kai-Yu Tseng, Wei-Ting Chao. The role of E-Cadherin mediated cell division in promoting collective colon cancer cell migration [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 2263.

Abstract Cell migration is regulated by multiple molecular pathways to change the morphology from epithelial to mesenchymal type and is important in cancer metastasis. In has been demonstrated epithelial mesenchymal transition (EMT) is related to E-cadherin expression level. The loss of E-cadherin expression results in tumor proliferation and metastasis. Recently, studies have been demonstrated the collective cancer cell migration which expresses high E-cadherin is a powerful mechanism of metastasis. Therefore, the role of E-cadherin in cancer metastasis is still not clear. Clathrin-mediated endocytosis (CME) was shown to regulate E-cadherin turnover on the membrane and the function of lysosome is also associated with cell vesicle trafficking, however, the role of lysosome in collective cell migration is not known. This study is investigating the role of lysosome in regulating E-cadherin dynamics through vesicle trafficking in collective colon cell migration. In the experiment, we used colon cancer cells with epithelial morphology and observed the relation of E-cadherin with endocytic protein clathrin, Rab5 and the recycling protein Rab11 in collective migrated cells. In the result, inhibition of lysosome activity by chloroquine treatment has great suppression effect on anchorage independent cell growth and inhibited collective cell migration. We observed that nocodazole treatment inhibited clathrin-mediated endocytosis, which caused E-cadherin to accumulate on the cell membrane. Western blot and confocal microscopy demonstrated chloroquine treatment induced Rab11 expression and accumulated in the cytosol which affected E-cadherin turnover. Our results demonstrated inhibits lysosome activity can suppress colon cancer cell growth and collective migration through lysosome mediated E-cadherin translocation. Chloroquine may be the potential treatment for colon cancer therapy. keywords: colon cancer, collective cell migration, E-cadherin, vesicle trafficking, lysosome Citation Format: Xiang-Ling Hou, Hui Min Koo, Yu-Cheng Weng, Yi-Wen Lu, Viriya Adhiguna Winarso, Yu-Lin Li, Wei-Ting Chao. Chloroquine inhibites Rab11 mediated E-cadherin transport in collective colon cancer cell migration [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 1582.

Abstract The most observed alteration in clear cell renal cell carcinoma (ccRCC) is the inactivation of the tumor suppressor von Hippel-Lindau (VHL) E3 ligase due to genetic predisposition, somatic mutations, or methylation. Loss of VHL can lead to hypoxia-inducible factor 2α (HIF-2α) accumulation and elevated expression of HIF target genes, such as VEGFA, many of which facilitate angiogenesis, proliferation, and metastasis of ccRCC. Therefore, inhibiting HIF-2α has become a new strategy for the treatment of ccRCC. Here, we present the discovery of BPI-452080, a selective small molecule HIF-2α inhibitor. In VHL defective ccRCC cell lines, BPI-452080 potently and selectively blocked the heterodimerization of HIF-2α with HIF-1β, but not that of HIF-1α with HIF-1β. It inhibited the downstream hypoxia-responsive gene transcription and VEGFA protein secretion. In multiple xenograft mouse models, oral administration of BPI-452080 significantly inhibited tumor growth in a dose-dependent manner. BPI-452080 demonstrated good PK/PD correlation in the 786-O xenograft model after a single dosing, as shown by a concentration-dependent inhibition of VEGFA secretion in plasma and a reduction of the mRNA levels of VEGFA, CXCR4, CCND1, and GLUT1 genes in tumor tissue. Moreover, BPI-452080 exhibited good bioavailability in multiple pre-clinical species, favorable ADME properties, and good tolerance in toxicology studies. In conclusion, BPI-452080 is a potent, selective, and orally bioavailable HIF-2α inhibitor which presents a novel therapeutic option for ccRCC, von Hippel-Lindau disease, and other solid tumors. BPI-452080 is planned to enter Phase I clinical trial in China in early 2023. Citation Format: Pingping Wang, Rongwen Yang, Yun Sun, Xuepeng Ju, Jiayu Zhao, Yanju Liu, Xiaoyun Liu, Zhengyao Zou, Jialin Ren, Min Wang, Haibo Chen, Xuegang Yi, Jian Zhang, Teng Ma, Gaoliang Cheng, Lijia Liu, Jing Guo, Xiangyong Liu, Hong Lan, Lieming Ding, Jiabing Wang. BPI-452080: A potent and selective HIF-2α inhibitor for the treatment of clear cell renal cell carcinoma, von Hippel-Lindau disease, and other solid tumors [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 494.

<p>「高文舉故事」始自形成，便以多元樣貌流播於各地聲腔，依據本文所較析的四個版本，彼此間存在著複雜關係，或有獨立發展者，如南管戲《高文舉》，或有屬古本系統者，如《水雲亭還魂記》，或有保留南戲原貌者莆仙戲《高文舉》，乃至於集大成者「文林閣本」《高文舉珍珠記》。南戲《高文舉》已亡佚，其中以《高文舉珍珠記》之影響最為深遠。「高文舉故事」主要情節有三：「珍珠米糷」、「還魂訴冤」、「包拯斷案」。在「文林閣本」與「莆仙本」皆有「珍珠米糷」、「龍圖斷案」，而「還魂本」有「玉真還魂」、「龍圖斷案」，至於「南管本」則一概具無，可知「南管本」在高文舉故事流變過程中之獨特性。本文主要針對各版本間之「關目情節」、「曲文賓白」等詳實比勘，剖析「高文舉」在不同聲腔劇種間之承繼與創新，並試圖重構各地聲腔在「高文舉」演化過程中之地位與價值。</p> <p>&nbsp;</p><p>Gao Wen Jyu of southern opera has been disappeared and present versions include Zhen Zhu Ji (Yi Yang tune), Gao Wen Jyu of Southern Pipes (Quan tune), Gao Wen Jyu of Pu Xian (Hsin Hua tune) and Revival After Death of Shui Yun Pavilion (Qing Yang tune). Among others, Zhen Zhu Ji is the most influential one. The plots such as &ldquo;Window Meeting&rdquo; and &ldquo;Zhen Zhu Mi Lan&rdquo; are not only the selected Zhe Zi operas for the later generations, but also the adapted texts of local operas. Main plots of &ldquo;story of Gao Wen Jyu&rdquo; are below: &ldquo;Zhen Zhu Mi Lan&rdquo;, &ldquo;Revival After Death to Appeal for Justice&rdquo; and &ldquo;Master Pao&rsquo;s Judgment&rdquo;. Zhen Zhu Ji and &ldquo;version of Pu Xian&rdquo; include &ldquo;Zhen Zhu Mi Lan&rdquo; and &ldquo;Master Pag&rsquo;s Judgment&rdquo;. &ldquo;Version of revival after death&rdquo; includes &ldquo;Revival After Death of Yu Chen&rdquo; and &ldquo;Master Pao&rsquo;s Judgment&rdquo;. &ldquo;Version of Southern Pipes&rdquo; does not include the above. Hence, it shows the uniqueness of &ldquo;version of Southern Pipes&rdquo; in the evolution of &ldquo;story of Gao Wen Jyu&rdquo;. Varieties of plots result in the richness of &ldquo;story of Gao Wen Jyu&rdquo;. The process of spread reveals flexibility and regionality of local common systematic tunes and varieties of operas. </p> <p> This study will treat four versions of Gao Wen Jyu as the subjects to significantly compare and analyze the original stories and difference and similarity of related work. First, it explores present versions to recognize the evolution of the story &ldquo;Gao Wen Jyu&rdquo;; secondly, it precisely compares &ldquo;plots&rdquo; and &ldquo;singing and talking&rdquo; of the versions to analyze the inheritance and innovation of &ldquo;story of Gao Wen Jyu&rdquo; in different common systematic tunes and varieties of Chinese operas. It, on the one hand, clarifies the relationship and origin of different versions of &ldquo;Gao Wen Jyu&rdquo; and, on the other hand, probes into cultural characteristics of &ldquo;time&rdquo; and &ldquo;region&rdquo; of operas; finally, it attmpets to reconstruct the positions and values of common systematic tunes in different regions in the evolution process of &ldquo;Gao Wen Jyu&rdquo;. </p> <p>&nbsp;</p>

Abstract Colorectal cancer is one of the most common cancer in the world. The mortality rate is the third among the top ten cancers. Among colorectal cancer patients, about 65-75% of patients have overexpression of epithelial growth factor receptors (EGFR). The antibody drug cetuximab that inhibits EGFR has also been developed. Moreover, overexpression of src protein is found in about 80% of patients with colorectal cancer. Higher levels of Src expression is related to the metastasis of colon cancer. Dasatinib is an oral taken tyrosine kinase inhibitor to inhibit the src phosphorylation. Therefore, in this study, the mechanism of cetuximab and dasatinib combined treatment in the orthotopic mouse model is investigated. The in vivo mechanism of EGFR and E-cadherin crosstalk in the mouse model is discussed. In this study, HT-29 colon cancer cells with BRAF V600E mutation were orthotopically injected into the cecum wall of BALB/c nude male mice. Two weeks later, cetuximab, dasatinib, and combined treatment of cetuximab and dasatinib were applied for three weeks. The tumor sizes were then recorded after sacrificed. Tumor Tissue were processed for tissue section with H&E staining. Immunohistochemistry (IHC) was applied to detect EGFR, p-Src, E-cadherin with specific antibodies. The protein expression levels were achieved by Western blot. In the results, the tumor size was smaller in cetuximab and dasatinib combined treated group. In IHC staining, the E-cadherin expression were not apparent in primary tumor site, however, were abundant in migrated cells. P-src expression was reduced in the dasatinib treated group and combined treatment group. In western blot result, the E-cadherin was increased after the treatment of dasatinib, and the p-src expression was inhibited after dasatinib treatment and combined treatment. Our results demonstrated cetuximab combined with dasatinib has the better result of suppression of BRAF mutated colon cancer cell growth and metastasis in the orthotopic mouse model. Citation Format: Yu-Cheng Weng, Yu-Lin Li, Xiang-Ling Hou, Hui Min Koo, Yi-Wen Lu, Viriya Adhiguna Winarso, Chia-Wen Lin, Wei-Ting Chao. The orthotopic mouse study of cetuximab and dasatinib treatment on BRAF mutated colon cancer cells [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 1626.

Abstract The mortality rate due to metastasis in cancer is as high as 90%. The underlying mechanisms have been studied, however, the process of metastasis is complicated, current therapies still cannot inhibit metastasis efficiently. In recent years, studies have mentioned that extracellular vesicles play an important role in cancer cell metastasis and tumor microenvironment. Extracellular vesicles can be divided into microvesicles, apoptotic bodies and exosomes, which can carry different substances into the tumor microenvironment. Especially exosomes, whose diameter is around 30-160nm, can carry DNA, RNA, miRNA, membrane proteins, lipids and other intracellular molecules into the cell through endocytosis for regulation. The process of metastasis and the drug resistance were also been demonstrated can be regulated by exosomes. At present, the physiological functions of exosomes are not clear. HT29 colon cancer cells previously discovered in our laboratory can have different responses to dasatinib treatment, and cells can be isolated to dasatinib selected cells(DSTS) and resistant cells(DSTR). In this study, the role of exosome upon dasatinib treatment in HT29 cell is investigated. In the experiment, exosomes from HT29, DSTS, and DSTR were isolated by ExoQuick-TC. Transmission electron microscope was used to observe the difference in exosome size. Exosomes from different cells were treated in HT29 cells, and differences at the protein and mRNA levels were observed using western blot and reverse transcription-polymerase chain reaction(RT-PCR). In my results, the diameter of exosomes in DSTS cells was smaller than that in DSTR and HT29 cells. The protein expression levels of Cavoelin-1 and Clathrin in HT29 were also increased in the treatment of exosome that from three types of cells. In addition, the DSTR derived-exosomes can induce the expression of pFAK and Clathrin mRNA in HT29 cells. The preliminary results suggest that DSTR derived-exosomes may affect cell migration. This study provides the clues that through understanding exosomes that secreted from different cells, cancer diagnosis and treatment can be conducted according to their characteristics, so as to reduce the possibility of cell metastasis precisely. Citation Format: Hui Min Koo, Yi-Wen Lu, Xiang-Ling Hou, Wei-Ting Chao. Investigates the role of exosomes in dasatinib treated HT29 colon cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6973.

Abstract Background:Olive oil has long been considered a healthier edible oil, rich in 75% oleic acid (OA) as its main component. OA is a monounsaturated fatty acid, and recent studies have shown that it is no longer limited to protecting cardiovascular and cerebrovascular systems, but can also reduce the risk of cancer. However, there is limited research on the specific mechanism. After fatty acid is ingested into the body, through fatty acids β-oxidation produces acetyl-CoA, which is a donor of protein acetylation. EMT is an important process to regulate tumor metastasis, and Zeb1 is one of the important EMT transcription factors. Therefore, we explored whether OA could inhibit the progress of breast cancer by affecting the acetylation modification of Zeb1. Methods: Western blotting, CCK8 assay, and Transwell were used to test the impact of gradient doses of OA on breast cancer cells. Immunoprecipitation and Immunoprecipitation mass spectrum were used to determine the acetylation modification sites of Zeb1. Coimmunoprecipitation, IF, and pull-down were used to test and verify the acetylase and deacetylase of Zeb1. Knockdown endogenous ZEB1 and then reconstructed stable cell lines of Zeb1 wild-type (Zeb1K1108WT), acetylation activated (Zeb1K1108Q), and inactivated mutants (Zeb1K1108R) by lentivirus. Detection of Zeb1 acetylation in patient tissue samples and mouse models under OA treatment using Zeb1-specific acetylation-modified antibodies. Results: OA inhibits the proliferation and migration of breast cancer cells in a concentration gradient-dependent manner, and inhibits the expression of Zeb1, N Cadherin, and upregulates E Cadherin. Among numerous fatty acids, only OA can promote the acetylation of Zeb1 by adjusting the ratio of acetyl-CoA and NAD+/NADH. K1108 is a biologically functional acetylation site of Zeb1, Zeb1K1108R exerts the cancer promoting function of Zeb1, while Zeb1K1108Q does not. OA can promote acetylation of Zeb1K1108WT, but cannot promote acetylation of Zeb1K1108R. Conclusions: OA inhibits the development of breast cancer through K1108 acetylation of Zeb1. These results suggest that breast cancer may be ameliorated through dietary interventions. Citation Format: Min Guo, Yanjin Wang, Yi Shi, Shuang Yang. OA inhibits the development of breast cancer through K1108 acetylation of Zeb1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 200.

Abstract Introduction: Comprehensive molecular profiling with combined DNA-RNA next-generation sequencing (NGS) on tumor tissue is now increasingly being used as standard-of-care for sequence therapy selection to improve cancer survival. Combined DNA-RNA NGS is also considered standard-of-care for central nervous system (CNS) tumor classification. Despite the genetic heterogeneity and diversity of cancers, most commercial combined DNA/RNA NGS assays are validated in Western populations, resulting in knowledge gaps in patient outcomes. We report here for the first time a range of actionable outcomes from a comprehensive DNA/RNA tissue NGS assay designed specifically to probe Asian-prevalent cancers and biomarkers in an international multicenter real-world study in Asia. Methods: 1,002 formalin-fixed paraffin-embedded tissue samples from 995 Asian cancer patients across &gt;70 centers in 7 countries and/or territories underwent real-world DNA/RNA NGS testing in a CAP-accredited CLIA-certified laboratory. Genomic alterations including SNVs, INDELS, gene fusions, CNVs, TMB, and MSI were analyzed using an Asian-centric pan-cancer hybrid-capture NGS panel that comprehensively profiles 572 cancer-related genes and 91 RNA fusion partners (UNITED). Biomarkers were considered actionable if the therapeutic indication in any solid tumor or hematological cancer was FDA-approved, guidelines-recommended, or supported by well-powered phase III clinical trials. Results: 27 cancer types were represented in 1,002 tissue samples, with lung, breast, colorectal, and prostate cancers comprising 45.5% of clinical volume. 79.5% of samples harbored ≥1 actionable biomarker, with the most frequently altered genes being TP53, KRAS, PIK3CA, EGFR, and NF1. Overall, 42.6% of samples had ≥1 biomarker with an indication in the patient’s cancer type, including 81.5% of lung, 59.0% of breast, 61.8% of colorectal, and 42.1% of prostate cancers. Across the pan-cancer cohort, 13.3% was TMB-high and 1.9% was MSI-high. 26.3% of samples were from cancer types outside the original assay design; the top 3 were pancreatic cancer (7.3%), sarcoma (3.3%), and CNS tumor (3.1%). Cancers of unknown primary (CUP) also constituted a significant proportion (3.8%). In CNS tumors, 38.7% harbored an actionable mutation in IDH1, BRAF, or H3-3A. In CUP, 78.8% harbored an actionable mutation; 50% of samples harbored biomarkers that additionally informed potential tumor origin, including mutations in EGFR, MET, ALK, ROS1, and BRCA1. Conclusion: The use of an Asian-focused pan-cancer DNA/RNA NGS panel resulted in detection of actionable biomarkers in 79.5% of clinical cases. These findings support the utility of DNA/RNA NGS assays in informing standard-of-care therapeutic decisions in Asian cancer patients for maximizing cancer survival. Citation Format: Jason Yongsheng Chan, Jing Yi Lee, Zi Yi Wan, Abner Herbert Lim, Tun Kiat Ko, Cedric Chuan-Young Ng, Donald Poon, Jens Samol, Tsz Him So, Su Pin Choo, Ravindran Kanesvaran, Cheng-Vai Hui, Joseph Siu-Kie Au, Aya El Helali, Timothy Yip, Vikneswari Rajasegaran, Sandy Lim, Ruifen Weng, Puay Hoon Tan, Bin Tean Teh, Min-Han Tan, Jonathan Poh. Real-world experience of an Asian pan-cancer combined DNA/RNA next generation sequencing (NGS) tissue biopsy assay [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6399.

Abstract Background: Resistance to chemotherapy remains an obstacle for triple-negative breast cancer (TNBC) patients. The core components of the ubiquitin-proteasome system have been demonstrated to regulate chemoresistance of TNBC. As a novel deubiquitinase (DUB), ubiquitin-specific peptidase 51 (USP51) plays a pivotal role in chemotherapeutic resistance in multiple malignancies. Herein, we sought to better understand how USP51 performs a cell-intrinsic role in mediating chemotherapeutic resistance in TNBC. Methods: Western blotting, RNA-sequencing and CCK8 assays were used to identify the DUBs for chemoresistance of breast cancer. Coimmunoprecipitation, GST-pulldown, protein deubiquitination and immunohistochemistry assays were then used to determine the biological phenotypes of ectopic USP51 in TNBC chemoresistance and associated signaling pathways in several different cell lines, mouse models and patient tissue samples. Ubiquitin-7-amido-4-methylcoumarin (Ub-AMC)-based deubiquitinase activity, cellular thermal shift and surface plasmon resonance (SPR) analyses were performed to investigate the activity of USP51 inhibitors. Results: To identify the critical DUBs involved in breast cancer chemoresistance, we established doxorubicin-resistant Cal51 and MDA-MB-231 TNBC cell lines by multiple dose exposure. We found ectopic USP51 in doxorubicin-resistant cells compared with their parental cells. Moreover, USP51-interfered chemoresistant tumor cells exhibited impaired cell viability as well as increased DNA damage and cell apoptosis upon treatment with doxorubicin. On the contrary, overexpression of USP51 performed the opposite effects to enhance cell viability but decrease DNA damage and apoptosis in response to doxorubicin; however, these outcomes were not shown for its catalytically inactive mutant USP51C372S. At the molecular level, GRP78 was identified as a bona fide substrate of USP51. Importantly, knockdown USP51 increased doxorubicin-induced DNA damage and apoptosis, which was rescued by overexpression of GRP78 in vitro and in vivo. In addition, the activity of ABCB1, the main efflux pump of doxorubicin, was enhanced by GRP78. Consistently, the expression of USP51, GRP78 and ABCB1 were correlated with chemoresistant phenotypes in TNBC patients. Of note, we also explored a small molecular inhibitor of USP51, WCY-4-1, which conferred chemosensitization in TNBC. Conclusion: These findings collectively indicated that ectopic USP51 enhances the activity of ABCB1 by deubiquitinating and stabilizing GRP78, which leads to decreased accumulation of doxorubicin as well as decreased DNA damage and cell apoptosis in TNBC. Our results also revealed that specific inhibition of USP51 significantly impairs doxorubicin-resistance in TNBC. Citation Format: Yang Ou, Kun Zhang, Qiuying Shuai, Chenyang Wang, Huayu Hu, Lixia Cao, Chunchun Qi, Min Guo, Zhaoxian Li, Jie Shi, Yuxin Liu, Siyu Zuo, Xiao Chen, Yanjing Wang, Mengdan Feng, Hang Wang, Yi Shi, Guang Yang, Shuang Yang. USP51-GRP78-ABCB1 axis promotes chemoresistance of triple negative breast cancer by decreasing the accumulation of doxorubicin in cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4556.

Abstract Purpose: No targeted therapy has been approved for NRAS-mutant melanoma. We evaluated the safety and tolerability and determined the recommended phase 2 dose (RP2D) of FCN-159, a selective MEK1/2 inhibitor, in patients with NRAS-mutant advanced melanoma. Methods: This single-arm, open-label, dose-escalation, phase 1A study in China (NCT03932253) enrolled patients with unresectable stage III/IV melanoma harboring NRAS mutations. Patients received FCN-159 in doses escalating from 0.2 mg until the maximum tolerated dose (MTD). Oral FCN-159 was given once in the single-dose period and once daily (QD) in 28-day cycles in the continuous-dose period. The primary endpoint was the incidence of dose-limiting toxicity (DLT). Results: As of September 16, 2021, 33 patients were enrolled and received 0.2-15 mg FCN-159. All patients had received systemic treatments. One DLT event (grade 3 folliculitis) occurred in the 15 mg group, and no DLT occurred at other dose levels; MTD was defined as 15 mg QD. Grade ≥3 treatment-emergent adverse events (TEAEs) deemed related to FCN-159 were reported in 5 (15.2%) patients across dose levels; stomatitis (2; 6.1%) was the most common. No FCN-159-related TEAEs were serious or led to treatment discontinuation. Among 21 patients assigned to doses ≥6 mg, 4 had investigator-confirmed objective responses (objective response rate, 19.0%; 95% confidence interval [CI], 5.4-41.9); all were partial responses (Table). Median DOR was 4.8 months (95% CI, 2.8-NE). Seven patients had SD (CBR, 52.4%; 95% CI, 29.8-74.3). Median progression-free survival was 3.8 months (95% CI, 1.8-5.6). FCN-159 12 mg QD was determined to be the RP2D per assessment of safety, antitumor activity, and pharmacokinetic data. Conclusion: FCN-159 was well tolerated and showed antitumor activity in patients with NRAS-mutant advanced melanoma. FCN-159 12 mg QD as a treatment for NRAS-mutant advanced melanoma warrants future investigation. Tumor response was assessed by the investigators according to Response Evaluation Criteria in Solid Tumors version 1.1.BOR, best overall response; CBR, clinical benefit rate; CR, complete response; DOR, duration of response; NA, not applicable; NE, not evaluable; NR, not reached; ORR, objective response rate; PD, progressive disease; PR, partial response; SD, stable disease. Table. Confirmed best overall response 6 mg(n = 5) 8 mg(n = 4) 12 mg(n = 6) 15 mg(n = 6) Total(N = 21) Confirmed BOR, n (%) CR 0 0 0 0 0 PR 2 (40.0) 1 (25.0) 0 1 (16.7) 4 (19.0) SD 1 (20.0) 1 (25.0) 3 (50.0) 2 (33.3) 7 (33.3) PD 2 (40.0) 2 (50.0) 1 (16.7) 2 (33.3) 7 (33.3) NE 0 0 2 (33.3) 1 (16.7) 3 (14.3) ORR, n (%), 95% CI 2 (40.0), 5.3–85.3 1 (25.0), 0.6–80.6 0 1 (16.7), 0.4–64.1 4 (19.0), 5.4–41.9 CBR, n (%), 95% CI 3 (60.0), 14.7–94.7 2 (50.0), 6.8–93.2 3 (50.0), 11.8–88.2 3 (50.0), 11.8–88.2 11 (52.4), 29.8–74.3 Median DOR (95% CI), months 4.8 (2.8–NE) NR (NE–NE) NA NR (NE–NE) 4.8 (2.8–NE) Citation Format: Lili Mao, Jun Guo, Lingjun Zhu, Yu Jiang, Wangjun Yan, Jian Zhang, Ai-min Hui, Zhuli Wu, Yuchen Yang, Han Zhao, Yiqian Jiang, Lu Si. FCN-159, a MEK1/2 inhibitor, in patients with advanced melanoma harboring NRAS mutations: A phase 1A dose-escalation study [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 CT519.

Abstract Background: Plasma-based tests to quantify circulating cell-free DNA cancer signal have emerged as viable applications across the cancer continuum, from early detection to optimal disease management. Here we demonstrate the feasibility of a tissue-agnostic, genome-wide methylome enrichment platform based on cell-free methylated DNA immunoprecipitation and high throughput sequencing (cfMEDIP-seq) for cancer detection, cancer signal quantification, and prognostication in head and neck cancer (HNC). Methods: Pre-treatment plasma samples from individuals with newly diagnosed stage I-IV HPV+ or HPV- HNC were analyzed with a bisulfite-free, non-degradative, genome-wide methylome enrichment platform using 5-10 ng of cell-free DNA. For cancer detection, a machine learning classifier used differentially methylated regions to distinguish cancers from non-cancer controls. The area under the receiver operating characteristic curve (AUC) and 95% confidence intervals were calculated. Cancer signals were quantified from average normalized counts across informative methylated regions and a 95% specificity threshold. For prognostication, events were defined as recurrence, progression, or death due to HNC, whichever occurred earliest. Time to event was compared for samples with cancer signal quantities above versus below the threshold. Post-treatment and longitudinal plasma samples from individuals with Stage I-IVB HNC (HPV+ and HPV- included) will be analyzed for recurrence prediction and detection of relapse. More than 100 patients and 300 samples will be analyzed. Results: For cancer detection, 92 pre-treatment plasma samples from HNC cases were distinguished from 674 controls with an AUC of 0.96 (0.94, 0.98). The AUC was 0.93 (0.86, 1.0) for Stage I, 0.93 (0.83, 1.0) for Stage II, 0.96 (0.94, 0.99) for Stage III, and 0.97 (0.96, 0.99) for Stage IV. For prognostication, 91 pre-treatment samples were included (7 stage I, 16 stage II, 23 stage III, 45 stage IV). Median follow-up time was 50.6 months with 27 events. Likelihood of recurrence or progression was significantly higher in samples with cancer signal above the threshold [hazard ratio 5.4 (95% CI 2.25, 12.95), log-rank P&lt;0.001]. In the upcoming analysis, data will be reported on the ability to predict recurrence and relapse in post-treatment samples. Conclusions: The cfMeDIP-seq approach demonstrated robust detection of HNC, across all stages and subtypes, and the ability to predict recurrence and progression from pre-treatment samples. We will report training data with cross validation to predict recurrence and relapse using post-treatment and longitudinal sampling. Collectively, data from these studies indicate that genome wide methylome enrichment has multiple use cases across the care continuum for patients with HNC. Citation Format: Geoffrey Liu, Jun Min, Yarong Wang, Justin Burgener, Ben Brown, Karen Budhraja, Junjun Zhang, Owen Hall, Shu Yi Shen, Martha Pienkowski, Shao Hui Huang, Laurie Ailles, Katrina Rey-McIntyre, Jeremy B. Provance, Eduardo Sosa, Cynthia Frye, Scott Bratman, Brian Allen, Joshua T. Jones, Abel Licon, Jing Zhang, Anne-Renee Hartman, Daniel D. De Carvalho. The development of a tissue-agnostic genome-wide methylome enrichment MRD assay for applications across the cancer care continuum for head and neck malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2427.

The need for clean and sustainable energy sources has witnessed a sudden upsurge in recent years owing to rising environmental degradation and climate disruption brought on by an overdependence on fossil fuels [1-3]. Electrochemical energy conversion technology is a crucial complement to the storage and on-demand utilization of renewable energy resources [4-6]. Rechargeable aqueous zinc ion batteries (AZIBs) have gained a significant research upsurge in recent times owing to their attractive potential for large-scale energy storage applications. In addition to low cost and naturally abundant raw materials, AZIBs technology offers competitive electrochemical performance and compatibility with water-based electrolyte systems, thereby eliminating the safety concerns associated with prevalent lithium-based battery technology. Moreover, multivalent AZIBs offer the opportunity to attain high energy and power density by permitting multiple electron transfers during reversible electrochemical operations [7]. In the context of AZIBs, significant research efforts are being actively pursued to develop high energy density cathode materials and to address the issue of Zn dendrite formation [8]. However, the selection of stable and low-cost current collectors is equally important as it serves as a bridge between the battery components and the external circuit, thereby influencing the battery capacity and its rate capability [9-10]. In this work, we have analyzed the electrochemical behavior of potential current collectors that are used globally in battery applications, namely Ni, Al, carbon paper, Cu mesh, graphite, and stainless steel in near-neutral aqueous ZnSO4 electrolyte (pH value = 5-6). The electrochemical stability of different current collectors has been investigated using linear sweep voltammetry and chronoamperometry techniques for their application as anode and cathode collectors. Scanning electron microscopy analysis has also been performed to understand the sign of corrosion post-electrochemical study. With stability up to 2.3 V w.r.t. Zn/Zn2+, Ni has proved to be the most corrosion-resistant current collector among the tested collectors on the cathode side. Although Zn itself is sufficiently stable at the anode side than any other current collector under the ZnSO4 electrolyte environment, Ni has shown considerable stability. Nonetheless, understanding the electrochemical stability of current collectors for AZIBs is a vital step in their design and future practical applications. References [1] Anand, Abhas, and Amitabh Shankar. "Study of Coal Cake Bulk Density and Its Shear Strength for Stamp Charging Coke Making Technique at Tata Steel." Coke and Chemistry 64, no. 7 (2021): 311-321. [2] Mukherjee, Subhrajit, Soumendu Boral, Hammad Siddiqi, Asmita Mishra, and Bhim Charan Meikap. "Present cum future of SARS-CoV-2 virus and its associated control of virus-laden air pollutants leading to potential environmental threat–A global review." Journal of Environmental Chemical Engineering 9, no. 2 (2021): 104973. [3] Singh, Manish Kr, Jayashree Pati, Deepak Seth, Jagdees Prasad, Manish Agarwal, M. Ali Haider, Jeng-Kuei Chang, and Rajendra S. Dhaka. "Diffusion mechanism and electrochemical investigation of 1T phase Al-MoS2@ rGO nano-composite as a high-performance anode for sodium-ion batteries." Chemical Engineering Journal (2022): 140140. [4] Dixit, Ram Ji, Kaustava Bhattacharyya, Vijay K. Ramani, and Suddhasatwa Basu. "Electrocatalytic hydrogenation of furfural using non-noble-metal electrocatalysts in alkaline medium." Green Chemistry 23, no. 11 (2021): 4201-4212. [5] Dixit, Ram Ji, and C. B. Majumder. "CO2 capture and electro-conversion into valuable organic products: A batch and continuous study." Journal of CO2 Utilization 26 (2018): 80-92. [6] Tiwari, Pankaj Kr, and Suddhasatwa Basu. "Testing of 5x5 cm2 Solid Oxide Fuel Cell in Direct Methane." ECS Transactions 91, no. 1 (2019): 349. [7] Li, Tian Chen, Daliang Fang, Jintao Zhang, Mei Er Pam, Zhi Yi Leong, Juezhi Yu, Xue Liang Li, Dong Yan, and Hui Ying Yang. "Recent progress in aqueous zinc-ion batteries: a deep insight into zinc metal anodes." Journal of Materials Chemistry A 9, no. 10 (2021): 6013-6028. [8] Guo, Na, Wenjie Huo, Xiaoyu Dong, Zhefei Sun, Yutao Lu, Xianwen Wu, Lei Dai et al. "A review on 3D zinc anodes for zinc ion batteries." Small Methods 6, no. 9 (2022): 2200597. [9] Kühnel, Ruben-Simon, and Andrea Balducci. "Comparison of the anodic behavior of aluminum current collectors in imide-based ionic liquids and consequences on the stability of high voltage supercapacitors." 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LANGUAGE NOTE | Document text in Chinese; abstract also in English. 本文主要分析香港20世紀六十年代的一本重要左派文藝刊物《海光文藝》中的流行小説。之前對《海光文藝》的研究主要在於它作爲左派的灰色刊物在冷戰時期的意義，本文則對其中的流行小説部分進行細讀，大致分爲兩個部分，第一部分討論《海光文藝》中對流行文學的研究，包括梁羽生、金庸對於武俠小説的討論，盈若思對瓊瑤及郭良蕙的言情小説的分析等。第二部分以文本細讀的方法，分析《海光文藝》刊登的流行短篇小説，特别是選取鄭慧、依達、亦舒這三個分别在五十年代、六十年代及七十年代最爲流行的言情作家作品來討論他們所寫作的言情小説中所反映的不同世代的創作特色。文章認爲《海光文藝》在評論及創作兩個方面均對當時的流行文學研究做出貢獻。它以一種嚴肅的、論文探討式的方式來分析時下的流行文學類型，同時，在創作上，刊物中發表的流行文學在世代、性别、背景上也有多樣化的特點，因此在香港六十年代流行文學的研究及創作上具有重要價值。 This paper discussed the popular fiction in Haiguang wenyi, one of the most important literary journals by the leftist in the 1960s Hong Kong. Previously the studies of this journal mainly focused on its significance as a grey journal of the leftists during the cold war, this paper, however, conducted a detailed analysis in its texts of popular fiction. It consisted two parts. Part one discussed the essays on the theory of popular literature published in this journal, including discussions on martial art fiction by Liang Yusheng and Jing Yong, the analysis by Ying Ruosi on the topic of romances of Qiong Yao and Guo Lianghui. Part two did a detailed readings of the popular fiction in this journal, especially the stories written by Zheng Hui, Yi Da and Yi Shu. These three writers were the most popular romance writers of the 50s, 60s and 70s each. In general, this paper argued that Haiguang wenyi contributed greatly to the popular literature writings in the 1960s Hong Kong literature. Not only did it take a serious attitude to treat popular literature at that time, but also the popular stories published in this journal exhibited the diversity of genres and generations at that time.

Graphene-based composites have received a great deal of attention in recent year because the presence of graphene can enhance the conductivity, strength of bulk materials and help create composites with superior qualities. Moreover, the incorporation of metal oxide nanoparticles such as Fe3O4 can improve the catalytic efficiency of composite material. In this work, we have synthesized a composite material with the combination of reduced graphene oxide (rGO), and Fe3O4 modified tissue-paper (mGO-PP) via a simple hydrothermal method, which improved the removal efficiency of the of methylene blue (MB) in water. MB blue is used as the model of contaminant to evaluate the catalytic efficiency of synthesized material by using a Fenton-like reaction. The obtained materials were characterized by SEM, XRD. The removal of materials with methylene blue is investigated by UV-VIS spectroscopy, and the result shows that mGO-PP composite is the potential composite for the color removed which has the removal efficiency reaching 65% in acetate buffer pH = 3 with the optimal time is 7 h. Keywords Graphene-based composite, methylene blue, Fenton-like reaction. References [1] Ma Joshi, Rue Bansal, Reng Purwar, Colour removal from textile effluents, Indian Journal of Fibre & Textile Research, 29 (2004) 239-259 http://nopr.niscair.res.in/handle/123456789/24631.[2] Kannan Nagar, Sundaram Mariappan, Kinetics and mechanism of removal of methylene blue by adsorption on various carbons-a comparative study, Dyes and pigments, 51 (2001) 25-40 https://doi.org/10.1016/S0143-7208(01)00056-0.[3] K Rastogi, J. N Sahu, B. C Meikap, M. N Biswas, Removal of methylene blue from wastewater using fly ash as an adsorbent by hydrocyclone, Journal of hazardous materials, 158 (2008) 531-540.https://doi.org/10.1016/j.jhazmat.2008.01. 105.[4] Qin Qingdong, Ma Jun, Liu Ke, Adsorption of anionic dyes on ammonium-functionalized MCM-41, Journal of Hazardous Materials, 162 (2009) 133-139 https://doi.org/10.1016/j.jhazmat. 2008.05.016.[5] Mui Muruganandham, Rps Suri, Sh Jafari, Mao Sillanpää, Lee Gang-Juan, Jaj Wu, Muo Swaminathan, Recent developments in homogeneous advanced oxidation processes for water and wastewater treatment, International Journal of Photoenergy, 2014 (2014). http://dx. doi.org/10.1155/2014/821674.[6] Herney Ramirez, Vicente Miguel , Madeira Luis Heterogeneous photo-Fenton oxidation with pillared clay-based catalysts for wastewater treatment: a review, Applied Catalysis B: Environmental, 98 (2010) 10-26 https://doi.org/ 10.1016/j.apcatb.2010.05.004.[7] Guo Rong, Jiao Tifeng, Li Ruifei, Chen Yan, Guo Wanchun, Zhang Lexin, Zhou Jingxin, Zhang Qingrui, Peng Qiuming, Sandwiched Fe3O4/carboxylate graphene oxide nanostructures constructed by layer-by-layer assembly for highly efficient and magnetically recyclable dye removal, ACS Sustainable Chemistry & Engineering, 6 (2017) 1279-1288 https://doi.org/10.1021/acssuschemeng.7b03635.[8] Sun Chao, Yang Sheng-Tao, Gao Zhenjie, Yang Shengnan, Yilihamu Ailimire, Ma Qiang, Zhao Ru-Song, Xue Fumin, Fe3O4/TiO2/reduced graphene oxide composites as highly efficient Fenton-like catalyst for the decoloration of methylene blue, Materials Chemistry and Physics, 223 (2019) 751-757 https://doi.org/ 10.1016/j.matchemphys.2018.11.056.[9] Guo Hui, Ma Xinfeng, Wang Chubei, Zhou Jianwei, Huang Jianxin, Wang Zijin, Sulfhydryl-Functionalized Reduced Graphene Oxide and Adsorption of Methylene Blue, Environmental Engineering Science, 36 (2019) 81-89 https://doi. org/10.1089/ees.2018.0157.[10] Zhao Lianqin, Yang Sheng-Tao, Feng Shicheng, Ma Qiang, Peng Xiaoling, Wu Deyi, Preparation and application of carboxylated graphene oxide sponge in dye removal, International journal of environmental research and public health, 14 (2017) 1301 https://doi.org/10.3390/ijerph14111301.[11] Yu Dandan, Wang Hua, Yang Jie, Niu Zhiqiang, Lu Huiting, Yang Yun, Cheng Liwei, Guo Lin, Dye wastewater cleanup by graphene composite paper for tailorable supercapacitors, ACS applied materials & interfaces, 9 (2017) 21298-21306 https://doi.org/10.1021/acsami.7b05318.[12] Wang Hou, Yuan Xingzhong, Wu Yan, Huang Huajun, Peng Xin, Zeng Guangming, Zhong Hua, Liang Jie, Ren MiaoMiao, Graphene-based materials: fabrication, characterization and application for the decontamination of wastewater and wastegas and hydrogen storage/generation, Advances in Colloid and Interface Science, 195 (2013) 19-40 https://doi. org/10.1016/j.cis.2013.03.009.[13] Marcano Daniela C, Kosynkin Dmitry V, Berlin Jacob M, Sinitskii Alexander, Sun Zhengzong, Slesarev Alexander, Alemany Lawrence B, Lu Wei, Tour James M, Improved synthesis of graphene oxide, ACS nano, 4 (2010) 4806-4814 https://doi.org/10.1021/nn1006368.[14] Zhang Jiali, Yang Haijun, Shen Guangxia, Cheng Ping, Zhang Jingyan, Guo Shouwu, Reduction of graphene oxide via L-ascorbic acid, Chemical Communications, 46 (2010) 1112-1114 http://doi. org/10.1039/B917705A [15] Gong Ming, Zhou Wu, Tsai Mon-Che, Zhou Jigang, Guan Mingyun, Lin Meng-Chang, Zhang Bo, Hu Yongfeng, Wang Di-Yan, Yang Jiang, Nanoscale nickel oxide/nickel heterostructures for active hydrogen evolution electrocatalysis, Nature communications, 5 (2014) 4695 https:// doi.org/10.1038/ncomms5695.[16] Wu Zhong-Shuai, Yang Shubin, Sun Yi, Parvez Khaled, Feng Xinliang, Müllen Klaus, 3D nitrogen-doped graphene aerogel-supported Fe3O4 nanoparticles as efficient electrocatalysts for the oxygen reduction reaction, Journal of the American Chemical Society, 134 (2012) 9082-9085 https://doi.org/10.1021/ja3030565.[17] Nguyen Son Truong, Nguyen Hoa Tien, Rinaldi Ali, Nguyen Nam Van, Fan Zeng, Duong Hai Minh, Morphology control and thermal stability of binderless-graphene aerogels from graphite for energy storage applications, Colloids and Surfaces A: Physicochemical and Engineering Aspects, 414 (2012) 352-358 https://doi.org/ 10.1016/j.colsurfa.2012.08.048.[18] Deng Yang, Englehardt James D, Treatment of landfill leachate by the Fenton process, Water research, 40 (2006) 3683-3694 https://doi.org/ 10.1016/j.watres.2006.08.009.

Nasopharyngeal carcinoma (NPC) is a head and neck cancer involving epithelial squamous-cell carcinoma of the nasopharynx that mainly occurs in individuals from East and Southeast Asia. We investigated whether Chinese herbal medicine (CHM) as a complementary therapy offers benefits to these patients. We retrospectively evaluated the Taiwan Cancer Registry (Long Form) database for patients with advanced NPC, using or not using CHM, between 2007–2013. Cox proportional-hazard model and Kaplan‒Meier survival analyses were applied for patient survival. CHM-users showed a lower overall and cancer-related mortality risk than non-users. For advanced NPC patients, the overall mortality risk was 0.799-fold for CHM-users, after controlling for age, gender, and Charlson comorbidity index (CCI) score (Cancer stages 3 + 4: adjusted hazard ratio [aHR]: 0.799, 95% confidence interval [CI]: 0.676–0.943, p = 0.008). CHM-users also showed a lower cancer-related mortality risk than non-users (aHR: 0.71, 95% CI: 0.53–0.96, p = 0.0273). Association rule analysis showed that CHM pairs were Ban-Zhi-Lian (BZL; Scutellaria barbata D.Don) and For single herbs, Bai-Hua-She-She-Cao (Herba Hedyotis Diffusae; Scleromitrion diffusum (Willd.) R.J.Wang (syn. Hedyotis diffusa Willd.) and Mai-Men-Dong (MMD; Ophiopogon japonicus (Thunb.) Ker Gawl.), and Gan-Lu-Yin (GLY) and BHSSC. Network analysis revealed that BHSSC was the core CHM, and BZL, GLY, and Xin-Yi-Qing-Fei-Tang (XYQFT) were important CHMs in cluster 1. In cluster 2, ShengDH, MMD, Xuan-Shen (XS; Scrophularia ningpoensis Hensl.), and Gua-Lou-Gen (GLG; Trichosanthes kirilowii Maxim.) were important CHMs. Thus, as a complementary therapy, CHM, and particularly the 8 CHMs identified, are important for the treatment of advanced NPC patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus , is causing a serious worldwide COVID-19 pandemic. The emergence of strains with rapid spread and unpredictable changes is the cause of the increase in morbidity and mortality rates. A number of drugs as well as vaccines are currently being used to relieve symptoms, prevent and treat the disease caused by this virus. However, the number of approved drugs is still very limited due to their effectiveness and side effects. In such a situation, medicinal plants and bioactive compounds are considered a highly valuable source in the development of new antiviral drugs against SARS-CoV-2. This review summarizes medicinal plants and bioactive compounds that have been shown to act on molecular targets involved in the infection and replication of SARS-CoV-2. Keywords: Medicinal plants, bioactive compounds, antivirus, SARS-CoV-2, COVID-19 References [1] R. Lu, X. Zhao, J. Li, P. Niu, B. Yang, H. 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Tencomnao, Anti-COVID-19 Drug Candidates: A Review on Potential Biological Activities of Natural Products in the Management of New Coronavirus Infection, Journal of Traditional and Complementary Medicine, Vol. 11, 2021, pp. 144-157, https://doi.org/10.1016/j.jtcme.2020.12.001.[6] R. E. Ferner, J. K. Aronson, Chloroquine and Hydroxychloroquine in Covid-19, BMJ, Vol. 369, 2020, https://doi.org/10.1136/bmj.m1432[7] J. Remali, W. M. Aizat, A Review on Plant Bioactive Compounds and Their Modes of Action Against Coronavirus Infection, Frontiers in Pharmacology, Vol. 11, 2021, https://doi.org/10.3389/fphar.2020.589044.[8] Y. Chen, Q. Liu, D. Guo, Emerging Coronaviruses: Genome Structure, Replication, and Pathogenesis, Medical Virology, Vol. 92, 2020, pp. 418‐423. https://doi.org/10.1002/jmv.25681.[9] B. Benarba, A. Pandiella, Medicinal Plants as Sources of Active Molecules Against COVID-19, Frontiers in Pharmacology, Vol. 11, 2020, https://doi.org/10.3389/fphar.2020.01189.[10] N. T. 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Introdução: O câncer é definido como uma proliferação descontrolada de células malignas em um hospedeiro e considerado uma das principais causas de morte em todo o mundo. No Brasil, o câncer colorretal é a segunda causa de morte mais comum entre mulheres e a terceira mais prevalente em homens. Muitas estratégias têm sido estudadas para auxiliar o tratamento antineoplásico. Dentro desse contexto, a ingestão de probióticos, representa uma nova opção terapêutica relevante no âmbito da nutrição. Objetivo: Realizar uma revisão sobre o uso dos probióticos no tratamento de pacientes com câncer colorretal. Material e Método: Trata-se de uma revisão realizada em 2018, utilizando-se 10 artigos, pesquisados nas bases indexadas BVS e PubMed e na ferramenta de pesquisa Google acadêmico. A pesquisa incluiu artigos em português e inglês publicados no período de 2010 a 2017. Resultados: O uso de probióticos demonstrou trazer efeitos positivos ao tratamento de pacientes com câncer colorretal, trazendo benefícios como: a diminuição de enterobactérias e enterococos, melhora na modulação da imunidade local, melhora dos sintomas intestinais, recuperação da função intestinal, entre outros. Conclusão: Conclui-se que apesar dos resultados positivos observados, há a necessidade de futuros estudos de longa duração para elucidar melhor essa relação.Descritores: Neoplasias Colorretais; Nutrientes; Probióticos.ReferênciasKahouli I, Malhotra M, Westfall S, Alaoui-Jamali MA, Prakash S. Design and validation of an orally administrated active L. fermentum-L. acidophilus probiotic formulation using colorectal cancer Apc Min/+ mouse model. Appl Microbiol Biotechnol. 2017;101(5):1999-2019.Oliveira RC, Rêgo MAV. Mortality risck of colorectal câncer in Brazil from 1980 to 2013. Arq Gastroenterol 2016;53(2)76-83.Instituto Nacional de Câncer (INCA). Tipos de câncer: colorretal. 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The curtain rose. The howling of desert wind filled the performance hall in the Shanghai Grand Theatre. Into the center stage, where a scenic construction of a mountain cliff and a desert landscape was dimly lit, entered the character of the Daoist priest Wang Yuanlu (1849–1931), performed by Chen Yizong. Dressed in a worn and dusty outfit of dark blue cotton, characteristic of Daoist priests, Wang began to sweep the floor. After a few moments, he discovered a hidden chambre sealed inside one of the rock sanctuaries carved into the cliff.Signaled by the quick, crystalline, stirring wave of sound from the chimes, a melodious Chinese ocarina solo joined in slowly from the background. Astonished by thousands of Buddhist sūtra scrolls, wall paintings, and sculptures he had just accidentally discovered in the caves, Priest Wang set his broom aside and began to examine these treasures. Dawn had not yet arrived, and the desert sky was pitch-black. Priest Wang held his oil lamp high, strode rhythmically in excitement, sat crossed-legged in a meditative pose, and unfolded a scroll. The sound of the ocarina became fuller and richer and the texture of the music more complex, as several other instruments joined in.Below is the opening scene of the award-winning, theatrical dance-drama Dunhuang, My Dreamland, created by China’s state-sponsored Lanzhou Song and Dance Theatre in 2000. Figure 1a: Poster Side A of Dunhuang, My Dreamland Figure 1b: Poster Side B of Dunhuang, My DreamlandThe scene locates the dance-drama in the rock sanctuaries that today are known as the Dunhuang Mogao Caves, housing Buddhist art accumulated over a period of a thousand years, one of the best well-known UNESCO heritages on the Silk Road. Historically a frontier metropolis, Dunhuang was a strategic site along the Silk Road in northwestern China, a crossroads of trade, and a locus for religious, cultural, and intellectual influences since the Han dynasty (206 B.C.E.–220 C.E.). Travellers, especially Buddhist monks from India and central Asia, passing through Dunhuang on their way to Chang’an (present day Xi’an), China’s ancient capital, would stop to meditate in the Mogao Caves and consult manuscripts in the monastery's library. At the same time, Chinese pilgrims would travel by foot from China through central Asia to Pakistan, India, Nepal, Bangladesh, and Sri Lanka, playing a key role in the exchanges between ancient China and the outside world. Travellers from China would stop to acquire provisions at Dunhuang before crossing the Gobi Desert to continue on their long journey abroad. Figure 2: Dunhuang Mogao CavesThis article approaches the idea of “abroad” by examining the present-day imagination of journeys along the Silk Road—specifically, staged performances of the various Silk Road journey-themed dance-dramas sponsored by the Chinese state for enhancing its cultural and foreign policies since the 1970s (Kuang).As ethnomusicologists have demonstrated, musicians, choreographers, and playwrights often utilise historical materials in their performances to construct connections between the past and the present (Bohlman; Herzfeld; Lam; Rees; Shelemay; Tuohy; Wade; Yung: Rawski; Watson). The ancient Silk Road, which linked the Mediterranean coast with central China and beyond, via oasis towns such as Samarkand, has long been associated with the concept of “journeying abroad.” Journeys to distant, foreign lands and encounters of unknown, mysterious cultures along the Silk Road have been documented in historical records, such as A Record of Buddhist Kingdoms (Faxian) and The Great Tang Records on the Western Regions (Xuanzang), and illustrated in classical literature, such as The Travels of Marco Polo (Polo) and the 16th century Chinese novel Journey to the West (Wu). These journeys—coming and going from multiple directions and to different destinations—have inspired contemporary staged performance for audiences around the globe.Home and Abroad: Dunhuang and the Silk RoadDunhuang, My Dreamland (2000), the contemporary dance-drama, staged the journey of a young pilgrim painter travelling from Chang’an to a land of the unfamiliar and beyond borders, in search for the arts that have inspired him. Figure 3: A scene from Dunhuang, My Dreamland showing the young pilgrim painter in the Gobi Desert on the ancient Silk RoadFar from his home, he ended his journey in Dunhuang, historically considered the northwestern periphery of China, well beyond Yangguan and Yumenguan, the bordering passes that separate China and foreign lands. Later scenes in Dunhuang, My Dreamland, portrayed through multiethnic music and dances, the dynamic interactions among merchants, cultural and religious envoys, warriors, and politicians that were making their own journey from abroad to China. The theatrical dance-drama presents a historically inspired, re-imagined vision of both “home” and “abroad” to its audiences as they watch the young painter travel along the Silk Road, across the Gobi Desert, arriving at his own ideal, artistic “homeland”, the Dunhuang Mogao Caves. Since his journey is ultimately a spiritual one, the conceptualisation of travelling “abroad” could also be perceived as “a journey home.”Staged more than four hundred times since it premiered in Beijing in April 2000, Dunhuang, My Dreamland is one of the top ten titles in China’s National Stage Project and one of the most successful theatrical dance-dramas ever produced in China. With revenue of more than thirty million renminbi (RMB), it ranks as the most profitable theatrical dance-drama ever produced in China, with a preproduction cost of six million RMB. The production team receives financial support from China’s Ministry of Culture for its “distinctive ethnic features,” and its “aim to promote traditional Chinese culture,” according to Xu Rong, an official in the Cultural Industry Department of the Ministry. Labeled an outstanding dance-drama of the Chinese nation, it aims to present domestic and international audiences with a vision of China as a historically multifaceted and cosmopolitan nation that has been in close contact with the outside world through the ancient Silk Road. Its production company has been on tour in selected cities throughout China and in countries abroad, including Austria, Spain, and France, literarily making the young pilgrim painter’s “journey along the Silk Road” a new journey abroad, off stage and in reality.Dunhuang, My Dreamland was not the first, nor is it the last, staged performances that portrays the Chinese re-imagination of “journeying abroad” along the ancient Silk Road. It was created as one of many versions of Dunhuang bihua yuewu, a genre of music, dance, and dramatic performances created in the early twentieth century and based primarily on artifacts excavated from the Mogao Caves (Kuang). “The Mogao Caves are the greatest repository of early Chinese art,” states Mimi Gates, who works to increase public awareness of the UNESCO site and raise funds toward its conservation. “Located on the Chinese end of the Silk Road, it also is the place where many cultures of the world intersected with one another, so you have Greek and Roman, Persian and Middle Eastern, Indian and Chinese cultures, all interacting. Given the nature of our world today, it is all very relevant” (Pollack). As an expressive art form, this genre has been thriving since the late 1970s contributing to the global imagination of China’s “Silk Road journeys abroad” long before Dunhuang, My Dreamland achieved its domestic and international fame. For instance, in 2004, The Thousand-Handed and Thousand-Eyed Avalokiteśvara—one of the most representative (and well-known) Dunhuang bihua yuewu programs—was staged as a part of the cultural program during the Paralympic Games in Athens, Greece. This performance, as well as other Dunhuang bihua yuewu dance programs was the perfect embodiment of a foreign religion that arrived in China from abroad and became Sinicized (Kuang). Figure 4: Mural from Dunhuang Mogao Cave No. 45A Brief History of Staging the Silk Road JourneysThe staging of the Silk Road journeys abroad began in the late 1970s. Historically, the Silk Road signifies a multiethnic, cosmopolitan frontier, which underwent incessant conflicts between Chinese sovereigns and nomadic peoples (as well as between other groups), but was strongly imbued with the customs and institutions of central China (Duan, Mair, Shi, Sima). In the twentieth century, when China was no longer an empire, but had become what the early 20th-century reformer Liang Qichao (1873–1929) called “a nation among nations,” the long history of the Silk Road and the colourful, legendary journeys abroad became instrumental in the formation of a modern Chinese nation of unified diversity rooted in an ancient cosmopolitan past. The staged Silk Road theme dance-dramas thus participate in this formation of the Chinese imagination of “nation” and “abroad,” as they aestheticise Chinese history and geography. History and geography—aspects commonly considered constituents of a nation as well as our conceptualisations of “abroad”—are “invariably aestheticized to a certain degree” (Bakhtin 208). Diverse historical and cultural elements from along the Silk Road come together in this performance genre, which can be considered the most representative of various possible stagings of the history and culture of the Silk Road journeys.In 1979, the Chinese state officials in Gansu Province commissioned the benchmark dance-drama Rain of Flowers along the Silk Road, a spectacular theatrical dance-drama praising the pure and noble friendship which existed between the peoples of China and other countries in the Tang dynasty (618-907 C.E.). While its plot also revolves around the Dunhuang Caves and the life of a painter, staged at one of the most critical turning points in modern Chinese history, the work as a whole aims to present the state’s intention of re-establishing diplomatic ties with the outside world after the Cultural Revolution. Unlike Dunhuang, My Dreamland, it presents a nation’s journey abroad and home. To accomplish this goal, Rain of Flowers along the Silk Road introduces the fictional character Yunus, a wealthy Persian merchant who provides the audiences a vision of the historical figure of Peroz III, the last Sassanian prince, who after the Arab conquest of Iran in 651 C.E., found refuge in China. By incorporating scenes of ethnic and folk dances, the drama then stages the journey of painter Zhang’s daughter Yingniang to Persia (present-day Iran) and later, Yunus’s journey abroad to the Tang dynasty imperial court as the Persian Empire’s envoy.Rain of Flowers along the Silk Road, since its debut at Beijing’s Great Hall of the People on the first of October 1979 and shortly after at the Theatre La Scala in Milan, has been staged in more than twenty countries and districts, including France, Italy, Japan, Thailand, Russia, Latvia, Hong Kong, Macao, Taiwan, and recently, in 2013, at the Lincoln Center for the Performing Arts in New York.“The Road”: Staging the Journey TodayWithin the contemporary context of global interdependencies, performing arts have been used as strategic devices for social mobilisation and as a means to represent and perform modern national histories and foreign policies (Davis, Rees, Tian, Tuohy, Wong, David Y. H. Wu). The Silk Road has been chosen as the basis for these state-sponsored, extravagantly produced, and internationally staged contemporary dance programs. In 2008, the welcoming ceremony and artistic presentation at the Olympic Games in Beijing featured twenty apsara dancers and a Dunhuang bihua yuewu dancer with long ribbons, whose body was suspended in mid-air on a rectangular LED extension held by hundreds of performers; on the giant LED screen was a depiction of the ancient Silk Road.In March 2013, Chinese president Xi Jinping introduced the initiatives “Silk Road Economic Belt” and “21st Century Maritime Silk Road” during his journeys abroad in Kazakhstan and Indonesia. These initiatives are now referred to as “One Belt, One Road.” The State Council lists in details the policies and implementation plans for this initiative on its official web page, www.gov.cn. In April 2013, the China Institute in New York launched a yearlong celebration, starting with "Dunhuang: Buddhist Art and the Gateway of the Silk Road" with a re-creation of one of the caves and a selection of artifacts from the site. In March 2015, the National Development and Reform Commission (NDRC), China’s top economic planning agency, released a new action plan outlining key details of the “One Belt, One Road” initiative. Xi Jinping has made the program a centrepiece of both his foreign and domestic economic policies. One of the central economic strategies is to promote cultural industry that could enhance trades along the Silk Road.Encouraged by the “One Belt, One Road” policies, in March 2016, The Silk Princess premiered in Xi’an and was staged at the National Centre for the Performing Arts in Beijing the following July. While Dunhuang, My Dreamland and Rain of Flowers along the Silk Road were inspired by the Buddhist art found in Dunhuang, The Silk Princess, based on a story about a princess bringing silk and silkworm-breeding skills to the western regions of China in the Tang Dynasty (618-907) has a different historical origin. The princess's story was portrayed in a woodblock from the Tang Dynasty discovered by Sir Marc Aurel Stein, a British archaeologist during his expedition to Xinjiang (now Xinjiang Uygur autonomous region) in the early 19th century, and in a temple mural discovered during a 2002 Chinese-Japanese expedition in the Dandanwulike region. Figure 5: Poster of The Silk PrincessIn January 2016, the Shannxi Provincial Song and Dance Troupe staged The Silk Road, a new theatrical dance-drama. Unlike Dunhuang, My Dreamland, the newly staged dance-drama “centers around the ‘road’ and the deepening relationship merchants and travellers developed with it as they traveled along its course,” said Director Yang Wei during an interview with the author. According to her, the show uses seven archetypes—a traveler, a guard, a messenger, and so on—to present the stories that took place along this historic route. Unbounded by specific space or time, each of these archetypes embodies the foreign-travel experience of a different group of individuals, in a manner that may well be related to the social actors of globalised culture and of transnationalism today. Figure 6: Poster of The Silk RoadConclusionAs seen in Rain of Flowers along the Silk Road and Dunhuang, My Dreamland, staging the processes of Silk Road journeys has become a way of connecting the Chinese imagination of “home” with the Chinese imagination of “abroad.” Staging a nation’s heritage abroad on contemporary stages invites a new imagination of homeland, borders, and transnationalism. Once aestheticised through staged performances, such as that of the Dunhuang bihua yuewu, the historical and topological landscape of Dunhuang becomes a performed narrative, embodying the national heritage.The staging of Silk Road journeys continues, and is being developed into various forms, from theatrical dance-drama to digital exhibitions such as the Smithsonian’s Pure Land: Inside the Mogao Grottes at Dunhuang (Stromberg) and the Getty’s Cave Temples of Dunhuang: Buddhist Art on China's Silk Road (Sivak and Hood). 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