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Article ; Online: Efficient 330-Gb/s PAM-8 modulation using silicon microring modulators.

Chan, David W U / Wu, Xiong / Lu, Chao / Lau, Alan Pak Tao / Tsang, Hon Ki

Optics letters

2022 Volume 48, Issue 4, Page(s) 1036–1039

Abstract: We propose and demonstrate a high-efficiency silicon microring modulator for next-generation optical transmitters operating at line rates above 300 Gb/s. The modulator supports high-order PAM-8 modulation up to 110 Gbaud (330 Gb/s), with a driving ... ...

Abstract	We propose and demonstrate a high-efficiency silicon microring modulator for next-generation optical transmitters operating at line rates above 300 Gb/s. The modulator supports high-order PAM-8 modulation up to 110 Gbaud (330 Gb/s), with a driving voltage of 1.8 V
Language	English
Publishing date	2022-09-28
Publishing country	United States
Document type	Journal Article
ISSN	1539-4794
ISSN (online)	1539-4794
DOI	10.1364/OL.479046
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Article ; Online: The Impact of the Tumor Microenvironment on Macrophage Polarization in Cancer Metastatic Progression.

Wang, Huogang / Yung, Mingo M H / Ngan, Hextan Y S / Chan, Karen K L / Chan, David W

International journal of molecular sciences

2021 Volume 22, Issue 12

Abstract: Rather than primary solid tumors, metastasis is one of the hallmarks of most cancer deaths. Metastasis is a multistage event in which cancer cells escape from the primary tumor survive in the circulation and disseminate to distant sites. According to ... ...

Abstract	Rather than primary solid tumors, metastasis is one of the hallmarks of most cancer deaths. Metastasis is a multistage event in which cancer cells escape from the primary tumor survive in the circulation and disseminate to distant sites. According to Stephen Paget's "Seed and Soil" hypothesis, metastatic capacity is determined not only by the internal oncogenic driving force but also by the external environment of tumor cells. Throughout the body, macrophages are required for maintaining tissue homeostasis, even in the tumor milieu. To fulfill these multiple functions, macrophages are polarized from the inflammation status (M1-like) to anti-inflammation status (M2-like) to maintain the balance between inflammation and regeneration. However, tumor cell-enforced tumor-associated macrophages (TAMs) (a high M2/M1 ratio status) are associated with poor prognosis for most solid tumors, such as ovarian cancer. In fact, clinical evidence has verified that TAMs, representing up to 50% of the tumor mass, exert both protumor and immunosuppressive effects in promoting tumor metastasis through secretion of interleukin 10 (IL10), transforming growth factor β (TGFβ), and VEGF, expression of PD-1 and consumption of arginine to inhibit T cell anti-tumor function. However, the underlying molecular mechanisms by which the tumor microenvironment favors reprogramming of macrophages to TAMs to establish a premetastatic niche remain controversial. In this review, we examine the latest investigations of TAMs during tumor development, the microenvironmental factors involved in macrophage polarization, and the mechanisms of TAM-mediated tumor metastasis. We hope to dissect the critical roles of TAMs in tumor metastasis, and the potential applications of TAM-targeted therapeutic strategies in cancer treatment are discussed.
MeSH term(s)	Animals ; Cell Differentiation ; Humans ; Immunotherapy/methods ; Neoplasm Metastasis ; Neoplasms/immunology ; Neoplasms/pathology ; Neoplasms/therapy ; Tumor Microenvironment ; Tumor-Associated Macrophages/immunology ; Tumor-Associated Macrophages/pathology
Language	English
Publishing date	2021-06-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22126560
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Article ; Online: New Insights into Ferroptosis Initiating Therapies (FIT) by Targeting the Rewired Lipid Metabolism in Ovarian Cancer Peritoneal Metastases.

Zhan, Shijie / Yung, Mingo M H / Siu, Michelle K Y / Jiao, Peili / Ngan, Hextan Y S / Chan, David W / Chan, Karen K L

International journal of molecular sciences

2022 Volume 23, Issue 23

Abstract: Ovarian cancer is one of the most lethal gynecological cancers worldwide. The poor prognosis of this malignancy is substantially attributed to the inadequate symptomatic biomarkers for early diagnosis and effective remedies to cure the disease against ... ...

Abstract	Ovarian cancer is one of the most lethal gynecological cancers worldwide. The poor prognosis of this malignancy is substantially attributed to the inadequate symptomatic biomarkers for early diagnosis and effective remedies to cure the disease against chemoresistance and metastasis. Ovarian cancer metastasis is often relatively passive, and the single clusters of ovarian cancer cells detached from the primary ovarian tumor are transcoelomic spread by the peritoneal fluid throughout the peritoneum cavity and omentum. Our earlier studies revealed that lipid-enriched ascitic/omental microenvironment enforced metastatic ovarian cancer cells to undertake metabolic reprogramming and utilize free fatty acids as the main energy source for tumor progression and aggression. Intriguingly, cell susceptibility to ferroptosis has been tightly correlated with the dysregulated fatty acid metabolism (FAM), and enhanced iron uptake as the prominent features of ferroptosis are attributed to the strengthened lipid peroxidation and aberrant iron accumulation, suggesting that ferroptosis induction is a targetable vulnerability to prevent cancer metastasis. Therefore, the standpoints about tackling altered FAM in combination with ferroptosis initiation as a dual-targeted therapy against advanced ovarian cancer were highlighted herein. Furthermore, a discussion on the prospect and challenge of inducing ferroptosis as an innovative therapeutic approach for reversing remedial resistance in cancer interventions was included. It is hoped this proof-of-concept review will indicate appropriate directions for speeding up the translational application of ferroptosis-inducing compounds (FINs) to improve the efficacy of ovarian cancer treatment.
Language	English
Publishing date	2022-12-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232315263
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Article ; Online: Orchestrated Action of AMPK Activation and Combined VEGF/PD-1 Blockade with Lipid Metabolic Tunning as Multi-Target Therapeutics against Ovarian Cancers.

Yung, Mingo M H / Siu, Michelle K Y / Ngan, Hextan Y S / Chan, David W / Chan, Karen K L

International journal of molecular sciences

2022 Volume 23, Issue 12

Abstract: Ovarian cancer is one of the most lethal gynecological malignancies worldwide, and chemoresistance is a critical obstacle in the clinical management of the disease. Recent studies have suggested that exploiting cancer cell metabolism by applying AMP- ... ...

Abstract	Ovarian cancer is one of the most lethal gynecological malignancies worldwide, and chemoresistance is a critical obstacle in the clinical management of the disease. Recent studies have suggested that exploiting cancer cell metabolism by applying AMP-activated protein kinase (AMPK)-activating agents and distinctive adjuvant targeted therapies can be a plausible alternative approach in cancer treatment. Therefore, the perspectives about the combination of AMPK activators together with VEGF/PD-1 blockade as a dual-targeted therapy against ovarian cancer were discussed herein. Additionally, ferroptosis, a non-apoptotic regulated cell death triggered by the availability of redox-active iron, have been proposed to be governed by multiple layers of metabolic signalings and can be synergized with immunotherapies. To this end, ferroptosis initiating therapies (FITs) and metabolic rewiring and immunotherapeutic approaches may have substantial clinical potential in combating ovarian cancer development and progression. It is hoped that the viewpoints deliberated in this review would accelerate the translation of remedial concepts into clinical trials and improve the effectiveness of ovarian cancer treatment.
MeSH term(s)	AMP-Activated Protein Kinases/metabolism ; Carcinoma, Ovarian Epithelial ; Female ; Humans ; Lipids/therapeutic use ; Ovarian Neoplasms/pathology ; Programmed Cell Death 1 Receptor ; Vascular Endothelial Growth Factor A/therapeutic use
Chemical Substances	Lipids ; Programmed Cell Death 1 Receptor ; Vascular Endothelial Growth Factor A ; AMP-Activated Protein Kinases (EC 2.7.11.31)
Language	English
Publishing date	2022-06-20
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23126857
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Article ; Online: C-band 67 GHz silicon photonic microring modulator for dispersion-uncompensated 100 Gbaud PAM-4.

Chan, David W U / Wu, Xiong / Zhang, Zunyue / Lu, Chao / Lau, Alan Pak Tao / Tsang, Hon Ki

Optics letters

2022 Volume 47, Issue 11, Page(s) 2935–2938

Abstract: A very-high-bandwidth integrated silicon microring modulator (MRM) designed on a commercial silicon photonics (SiP) platform for C-band operation is presented. The MRM has a 3 dB electro-optic (EO) bandwidth of over 67 GHz and features a small footprint ... ...

Abstract	A very-high-bandwidth integrated silicon microring modulator (MRM) designed on a commercial silicon photonics (SiP) platform for C-band operation is presented. The MRM has a 3 dB electro-optic (EO) bandwidth of over 67 GHz and features a small footprint of 24 µm × 70 µm. Using the MRM, we demonstrate intensity modulation-direct detection (IM-DD) transmission with 4-level pulse amplitude modulation (PAM-4) signaling of over 100 Gbaud. By utilizing the optical peaking effect and negative chirp in the MRM, we extend the transmission distance, which is limited by the fiber-dispersion-induced frequency fading. Using a standard single-mode fiber (SSMF) for transmission across distances of up to 2 km, we measured the data transmission of 100 Gbaud PAM-4 signals with a bit error rate (BER) under the general 7% hard-decision forward-error correction (HD-FEC) threshold. The MRM enables an extended transmission distance for 100 Gbaud signaling in the C-band without dispersion compensation.
Language	English
Publishing date	2022-05-25
Publishing country	United States
Document type	Journal Article
ISSN	1539-4794
ISSN (online)	1539-4794
DOI	10.1364/OL.460602
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Article: The Stress-Inducible BCL2A1 Is Required for Ovarian Cancer Metastatic Progression in the Peritoneal Microenvironment.

Liang, Rui / Yung, Mingo M H / He, Fangfang / Jiao, Peili / Chan, Karen K L / Ngan, Hextan Y S / Chan, David W

Cancers

2021 Volume 13, Issue 18

Abstract: Emerging evidence indicates that hypoxia plays a critical role in governing the transcoelomic metastasis of ovarian cancer. Hence, targeting hypoxia may be a promising approach to prevent the metastasis of ovarian cancer. Here, we report that BCL2A1, a ... ...

Abstract	Emerging evidence indicates that hypoxia plays a critical role in governing the transcoelomic metastasis of ovarian cancer. Hence, targeting hypoxia may be a promising approach to prevent the metastasis of ovarian cancer. Here, we report that BCL2A1, a BCL2 family member, acts as a hypoxia-inducible gene for promoting tumor progression in ovarian cancer peritoneal metastases. We demonstrated that BCL2A1 was induced not only by hypoxia but also other physiological stresses through NF-κB signaling and then was gradually reduced by the ubiquitin-proteasome pathway in ascites-derived ovarian cancer cells. The upregulated BCL2A1 was frequently found in advanced metastatic ovarian cancer cells, suggesting its clinical relevance in ovarian cancer metastatic progression. Functionally, BCL2A1 enhanced the foci formation ability of ovarian cancer cells in a stress-conditioned medium, colony formation in an ex vivo omental tumor model, and tumor dissemination in vivo. Under stress conditions, BCL2A1 accumulated and colocalized with mitochondria to suppress intrinsic cell apoptosis by interacting with the BH3-only subfamily BCL2 members HRK/BAD/BID in ovarian cancer cells. These findings indicate that BCL2A1 is an early response factor that maintains the survival of ovarian cancer cells in the harsh tumor microenvironment.
Language	English
Publishing date	2021-09-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13184577
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Article ; Online: Identification of calcium and integrin-binding protein 1 as a reprogrammed glucose metabolism mediator to restrict immune cell infiltration in the stromal compartment of pancreatic ductal adenocarcinoma.

Ma, Junrui / Song, Yue / Zhuang, Tongtao / Yang, Hao / Yang, Xiaobao / Zheng, Juanjuan / Luo, Jiajun / Xia, Yihan / Fei, Xuefeng / Chan, David W / Wu, Di / Xu, Peiqing / Ni, Peihua / Dai, Jing / Xu, Dakang / Hu, Yiqun

Frontiers in immunology

2023 Volume 14, Page(s) 1158964

Abstract: An increasing body of evidence has suggested that reprogrammed metabolism plays a critical role in the progression of pancreatic ductal adenocarcinoma (PDAC) by affecting the tumor and stromal cellular components in the tumor microenvironment (TME). By ... ...

Abstract	An increasing body of evidence has suggested that reprogrammed metabolism plays a critical role in the progression of pancreatic ductal adenocarcinoma (PDAC) by affecting the tumor and stromal cellular components in the tumor microenvironment (TME). By analyzing the KRAS pathway and metabolic pathways, we found that calcium and integrin-binding protein 1 (CIB1) corresponded with upregulation of glucose metabolism pathways and was associated with poor prognosis in patients with PDAC from The Cancer Genome Atlas (TCGA). Elevated CIB1 expression combined with upregulated glycolysis, oxidative phosphorylation (Oxphos), hypoxia pathway activation, and cell cycle promoted PDAC tumor growth and increased tumor cellular com-ponents. Furthermore, we confirmed the mRNA overexpression of CIB1 and co-expression of CIB1 and KRAS mutation in cell lines from the Expression Atlas. Subsequently, immunohistochemistry staining from the Human Protein Atlas (HPA) showed that high expression of CIB1 in tumor cells was associated with an increased tumor compartment and reduced stromal cellular abundance. Furthermore, using multiplexed immunohistochemistry (mIHC), we verified that low stromal abundance was correlated with low infiltration of CD8
MeSH term(s)	Humans ; Calcium/metabolism ; Carcinoma, Pancreatic Ductal/pathology ; Glucose ; Integrins/metabolism ; Pancreatic Neoplasms/pathology ; Proto-Oncogene Proteins p21(ras)/genetics ; Tumor Microenvironment ; Pancreatic Neoplasms
Chemical Substances	Calcium (SY7Q814VUP) ; Glucose (IY9XDZ35W2) ; Integrins ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; CIB1 protein, human
Language	English
Publishing date	2023-04-28
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1158964
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Article ; Online: Tumor-secreted exosomal miR-141 activates tumor-stroma interactions and controls premetastatic niche formation in ovarian cancer metastasis.

Mo, Yulan / Leung, Leanne L / Mak, Celia S L / Wang, Xueyu / Chan, Wai-Sun / Hui, Lynn M N / Tang, Hermit W M / Siu, Michelle K Y / Sharma, Rakesh / Xu, Dakang / Tsui, Stephen K W / Ngan, Hextan Y S / Yung, Mingo M H / Chan, Karen K L / Chan, David W

Molecular cancer

2023 Volume 22, Issue 1, Page(s) 4

Abstract: Background: Metastatic colonization is one of the critical steps in tumor metastasis. A pre-metastatic niche is required for metastatic colonization and is determined by tumor-stroma interactions, yet the mechanistic underpinnings remain incompletely ... ...

Abstract	Background: Metastatic colonization is one of the critical steps in tumor metastasis. A pre-metastatic niche is required for metastatic colonization and is determined by tumor-stroma interactions, yet the mechanistic underpinnings remain incompletely understood. Methods: PCR-based miRNome profiling, qPCR, immunofluorescent analyses evaluated the expression of exosomal miR-141 and cell-to-cell communication. LC-MS/MS proteomic profiling and Dual-Luciferase analyses identified YAP1 as the direct target of miR-141. Human cytokine profiling, ChIP, luciferase reporter assays, and subcellular fractionation analyses confirmed YAP1 in modulating GROα production. A series of in vitro tumorigenic assays, an ex vivo model and Yap1 stromal conditional knockout (cKO) mouse model demonstrated the roles of miR-141/YAP1/GROα/CXCR1/2 signaling cascade. RNAi, CRISPR/Cas9 and CRISPRi systems were used for gene silencing. Blood sera, OvCa tumor tissue samples, and tissue array were included for clinical correlations. Results: Hsa-miR-141-3p (miR-141), an exosomal miRNA, is highly secreted by ovarian cancer cells and reprograms stromal fibroblasts into proinflammatory cancer-associated fibroblasts (CAFs), facilitating metastatic colonization. A mechanistic study showed that miR-141 targeted YAP1, a critical effector of the Hippo pathway, reducing the nuclear YAP1/TAZ ratio and enhancing GROα production from stromal fibroblasts. Stromal-specific knockout (cKO) of Yap1 in murine models shaped the GROα-enriched microenvironment, facilitating in vivo tumor colonization, but this effect was reversed after Cxcr1/2 depletion in OvCa cells. The YAP1/GROα correlation was demonstrated in clinical samples, highlighting the clinical relevance of this research and providing a potential therapeutic intervention for impeding premetastatic niche formation and metastatic progression of ovarian cancers. Conclusions: This study uncovers miR-141 as an OvCa-derived exosomal microRNA mediating the tumor-stroma interactions and the formation of tumor-promoting stromal niche through activating YAP1/GROα/CXCRs signaling cascade, providing new insight into therapy for OvCa patients with peritoneal metastases.
MeSH term(s)	Humans ; Animals ; Mice ; Female ; Chromatography, Liquid ; Proteomics ; Tandem Mass Spectrometry ; Ovarian Neoplasms/genetics ; MicroRNAs/genetics ; Adaptor Proteins, Signal Transducing/genetics ; Tumor Microenvironment
Chemical Substances	MicroRNAs ; Adaptor Proteins, Signal Transducing ; MIRN141 microRNA, human
Language	English
Publishing date	2023-01-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2091373-4
ISSN	1476-4598 ; 1476-4598
ISSN (online)	1476-4598
ISSN	1476-4598
DOI	10.1186/s12943-022-01703-9
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Article ; Online: SCD1/FADS2 fatty acid desaturases equipoise lipid metabolic activity and redox-driven ferroptosis in ascites-derived ovarian cancer cells.

Xuan, Yang / Wang, Huogang / Yung, Mingo Mh / Chen, Fushun / Chan, Wai-Sun / Chan, Yau-Sang / Tsui, Stephen Kw / Ngan, Hextan Ys / Chan, Karen Kl / Chan, David W

Theranostics

2022 Volume 12, Issue 7, Page(s) 3534–3552

Abstract: Rationale: ...

Abstract	Rationale:
MeSH term(s)	Animals ; Ascites ; Carcinoma, Ovarian Epithelial ; Cisplatin/pharmacology ; Delta-5 Fatty Acid Desaturase ; Fatty Acid Desaturases/genetics ; Fatty Acid Desaturases/metabolism ; Fatty Acids, Unsaturated ; Female ; Ferroptosis ; Humans ; Iron ; Mice ; Ovarian Neoplasms/drug therapy ; Oxidation-Reduction ; Peritoneal Neoplasms ; Stearoyl-CoA Desaturase/genetics ; Stearoyl-CoA Desaturase/metabolism ; Tumor Microenvironment
Chemical Substances	Delta-5 Fatty Acid Desaturase ; Fatty Acids, Unsaturated ; Iron (E1UOL152H7) ; Fatty Acid Desaturases (EC 1.14.19.-) ; SCD1 protein, human (EC 1.14.19.1) ; Scd1 protein, mouse (EC 1.14.19.1) ; Stearoyl-CoA Desaturase (EC 1.14.19.1) ; FADS2 protein, human (EC 1.14.19.3) ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2022-04-24
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2592097-2
ISSN	1838-7640 ; 1838-7640
ISSN (online)	1838-7640
ISSN	1838-7640
DOI	10.7150/thno.70194
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Article: PFKFB3 Regulates Chemoresistance, Metastasis and Stemness

Jiang, Yu-Xin / Siu, Michelle K Y / Wang, Jing-Jing / Leung, Thomas H Y / Chan, David W / Cheung, Annie N Y / Ngan, Hextan Y S / Chan, Karen K L

Frontiers in oncology

2022 Volume 12, Page(s) 748403

Abstract: Glycolysis has been reported to be critical for cancer stem cells (CSCs), which are associated with tumor chemoresistance, metastasis and recurrence. Thus, selectively targeting glycolytic enzymes may be a potential therapy for ovarian cancer. 6- ... ...

Abstract	Glycolysis has been reported to be critical for cancer stem cells (CSCs), which are associated with tumor chemoresistance, metastasis and recurrence. Thus, selectively targeting glycolytic enzymes may be a potential therapy for ovarian cancer. 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), the main source of fructose-2,6-bisphosphate, controls the first committed step in glycolysis. We investigate the clinical significance and roles of PFKFB3 in ovarian cancer using
Language	English
Publishing date	2022-01-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.748403
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