Article
Oncology
Zhuna Wu, Chunxian Huang, Ruixin Li, Hui Li, Huaiwu Lu, Zhongqiu Lin
Summary: Impaired radiosensitivity is a major cause of therapeutic failures in cervical cancer patients undergoing radical radiotherapy. The PRKCI gene, which exhibits tumor-specific copy number amplification in cervical cancer, is found to decrease radiosensitivity by modulating the Hh/GLI1 pathway.
FRONTIERS IN ONCOLOGY
(2022)
Article
Pharmacology & Pharmacy
Minyu Wang, Wanying Huang
Summary: This study found that FOXS1 activates the Hedgehog (Hh) signaling pathway by blocking the ubiquitination of Gli1, thereby promoting the growth and metastasis of prostate cancer cells. High levels of FOXS1 were associated with worse tumor stage and shorter survival in prostate cancer patients.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Oncology
Justin T. Avery, Ruowen Zhang, Rebecca J. Boohaker
Summary: GLI1, a transcriptional effector in the Hedgehog signaling pathway, is tightly regulated during normal tissue development but aberrant activation in cancer can promote hallmarks such as proliferation, metastasis, and chemoresistance. Its oncogenic activities mainly involve regulating cell cycle, DNA replication, and DNA damage repair processes. Understanding the mechanisms of GLI1 dysregulation can provide prognostic and diagnostic biomarkers for targeted therapy in cancer treatment.
FRONTIERS IN ONCOLOGY
(2021)
Article
Plant Sciences
Jing Chen, Da Ma, Cuicui Zeng, Lorenzo V. White, Huanqing Zhang, Yinglai Teng, Ping Lan
Summary: The steroidal alkaloid solasodine has been found to directly suppress Hh/Gli1 signaling, inhibiting the proliferation and self-renewal ability of cancer stem-like cells (CSCs). This compound may serve as a novel anticancer candidate targeting CSCs.
Article
Plant Sciences
Mengjie Li, Tingting Guo, Jiayi Lin, Xia Huang, Qiaodan Ke, Yujian Wu, Chunping Fang, Chenxia Hu
Summary: Curcumin, the main pharmacological component extracted from Curcuma longa L, has been found to inhibit proliferation and metastasis of TNBC cells via the Hedgehog/Gli1 pathway, providing potential therapeutic strategies for TNBC.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
ZhongWei Wang, YaLi Wang, XiuLong Ma, ChengXue Dang
Summary: The study revealed that elevated expression of RSPO2 in nasopharyngeal carcinoma promotes cell survival and proliferation, while its silencing inhibits migration and invasion through regulation of EMT-related proteins and the ZNRF3/Hedgehog-Gli1 signaling pathway.
Article
Cell & Tissue Engineering
Yekaterina Galat, Haigang Gu, Mariana Perepitchka, Robert Taylor, Joon Won Yoon, Xenia A. Glukhova, Xiao-Nan Li, Igor P. Beletsky, David O. Walterhouse, Vasiliy Galat, Philip M. Iannaccone
Summary: This study investigated the impact of editing GLI1 gene in human embryonic stem cells, revealing the critical role of GLI1 intronic region in the feedback loop and lineage-specific effects on stem cell differentiation. Editing this region resulted in delayed neural commitment, inhibition of endodermal and mesodermal differentiation, and altered expression of osteogenic markers and cancer-related genes. Inhibition of GLI1 had similar effects, indicating potential therapeutic implications.
Article
Medicine, General & Internal
Yake Liu, Shaohua Liu, Zhe Song, Daoyun Chen, Zoe Album, Samuel Green, Xianghua Deng, Scott A. Rodeo
Summary: The role of Gli1 in tendon-bone healing after ACLR has been investigated, and it has been found that Gli1 deficiency impairs the healing process. This finding provides insight into the molecular mechanism of tendon-bone healing and suggests Gli1 as a potential therapeutic target for improving ACLR outcomes.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Cell Biology
Taghi Manshouri, Ivo Veletic, Ping Li, C. Cameron Yin, Sean M. Post, Srdan Verstovsek, Zeev Estrov
Summary: GF1 is highly expressed in BM fibrocytes of MF patients, affecting fibrocyte-induced BM fibrosis by influencing MMP levels, and STAT3-activated GLI1 is also involved in the fibrosis process.
CELL DEATH & DISEASE
(2022)
Review
Cell Biology
Dian Jing, Chaoyuan Li, Ke Yao, Xudong Xie, Peiqi Wang, Hu Zhao, Jian Q. Feng, Zhihe Zhao, Yafei Wu, Jun Wang
Summary: Gli1(+) MSCs, as a type of crucial mesenchymal stem cells, are responsible for various tissue developments, homeostasis, and injury repair. They play critical roles in the development and homeostasis of a variety of hard and soft tissues.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jiachen Wen, Radha Charan Dash, Angela M. Zaino, Noah J. Harrahill, Jackson T. Calhoun, Christopher O. Dusek, Shana R. Morel, Matthew Russolillo, Kyle Hadden
Summary: Aberrant activation of the Hedgehog (Hh) signaling pathway is common in various human malignancies. GLI1, the ultimate effector of the pathway, has been identified as a regulator of tumorigenic pathways in Hh-independent cancers. A systematic study on a GLI1 inhibitor led to the discovery of an enhanced inhibitor with improved activity (compound 39), and suggested a potential role for SRC family kinases in regulating oncogenic GLI1 transcriptional activity.
BIOORGANIC CHEMISTRY
(2023)
Article
Biotechnology & Applied Microbiology
Qing Wang, Wei Zhang, Xiaole Peng, Yunxia Tao, Ye Gu, Wenming Li, Xiaolong Liang, Liangliang Wang, Zerui Wu, Tianhao Wang, Haifeng Zhang, Xin Liu, Yaozeng Xu, Yu Liu, Jun Zhou, Dechun Geng
Summary: Wear particle-induced periprosthetic osteolysis poses a severe threat to global public health and is a major cause of joint arthroplasty failure and secondary surgery. The study reveals that the Hh-Gli1 signaling cascade, mediated through GSK-3 beta, is involved in titanium nanoparticle-induced osteolysis.
JOURNAL OF NANOBIOTECHNOLOGY
(2022)
Article
Cell Biology
Davide Vecchiotti, Daniela Verzella, Mauro Di Vito Nolfi, Daniel D'Andrea, Irene Flati, Barbara Di Francesco, Jessica Cornice, Edoardo Alesse, Daria Capece, Francesca Zazzeroni
Summary: The NF-kappa B-SHh-GLI1 axis plays an important role in advanced prostate cancer and its elevation is associated with worse prognosis, suggesting it could be a target for treating aggressive prostate cancer.
Article
Biochemistry & Molecular Biology
Xiangyang Li, Rui Sun, Hao Wu, Chaonan Zheng, Ya-Qiu Long
Summary: English Summary: The Hedgehog/Glioma-associated oncogene (Hh/Gli) signaling pathway is crucial for embryonic development and tissue homeostasis, and its dysregulation is associated with various human malignancies. Gli1, a downstream transcription factor of the Hh pathway, is a common regulator of tumorigenic pathways in Hh-independent cancers, making it a promising drug target. However, the development of small molecules that target Gli1 protein has been slow due to lack of efficacy and selectivity. In this study, researchers developed novel Gli1 degraders based on the hydrophobic tagging (HyT) strategy, which effectively inhibited the proliferation of colorectal cancer cells and induced Gli1 degradation. These small molecules showed stronger potency in suppressing Hh target genes compared to the canonical Hh antagonist Vismodegib, and they overcame resistance to current Smoothened (SMO) antagonists. This study provides a new avenue for developing therapeutic approaches targeting the Hh/Gli1 signaling pathway.
BIOORGANIC CHEMISTRY
(2023)
Article
Immunology
Guido Hernan Falduto, Annika Pfeiffer, Qunshu Zhang, Yuzhi Yin, Dean Darrel Metcalfe, Ana Olivera
Summary: The GLI proteins play a critical role in regulating the survival and proliferation of mast cells. Inhibition of GLI activity leads to increased apoptosis and reduced mast cell numbers. GLI silencing also inhibits the proliferation of neoplastic mast cell lines.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Emergency Medicine
Lee-Kwan Chuk, Josephine Yuen-Man Chung, Henry Hing-Wai Lau, Ling Yan Leung, Kevin K. C. Hung, Colin A. Graham
Summary: This study investigates the utility of a modified version of the Edinburgh Red Eye Diagnostic Algorithm used by emergency nurse practitioners. The results show that emergency nurse practitioners achieve similar patient-reported outcomes compared to emergency doctors in managing red eye patients using the algorithm. There was a reduction in symptom severity in both groups and no significant difference in symptom resolution between the two groups.
HONG KONG JOURNAL OF EMERGENCY MEDICINE
(2022)
Article
Emergency Medicine
Howard Tat Chun Chan, Ling Yan Leung, Alex Kwok Keung Law, Chi Hung Cheng, Colin A. Graham
Summary: This study investigated acute pyelonephritis patients treated in the emergency medicine ward at Prince of Wales Hospital in Hong Kong and found that elevated C-reactive protein levels and not receiving antibiotics in the emergency department were associated with prolonged hospital length of stay.
HONG KONG JOURNAL OF EMERGENCY MEDICINE
(2023)
Article
Emergency Medicine
Kei Ching Kevin Hung, Chun Yu Lai, Janice Hiu Hung Yeung, Marc Maegele, Po Shan Lily Chan, Ming Leung, Hay Tai Wong, John Kit Shing Wong, Ling Yan Leung, Marc Chong, Chi Hung Cheng, Nai Kwong Cheung, Colin Alexander Graham
Summary: The study compared the mortality prediction model using TRISS and RISC II for trauma center patients in Hong Kong, finding that RISC II was superior in predicting the 30-day mortality for adult blunt major trauma patients in Hong Kong.
EUROPEAN JOURNAL OF TRAUMA AND EMERGENCY SURGERY
(2022)
Article
Cell Biology
Jing Li, Ruiqin Wu, Mingo M. H. Yung, Jing Sun, Zhuqing Li, Hai Yang, Yi Zhang, Stephanie S. Liu, Annie N. Y. Cheung, Hextan Y. S. Ngan, John C. Braisted, Wei Zheng, Huiqiang Wei, Yingtang Gao, Peter Nemes, Huadong Pei, David W. Chan, Yiliang Li, Wenge Zhu
Summary: The JAK2/STAT pathway is hyperactivated in many cancers, leading to poor clinical prognosis and drug resistance. The protease SENP1 interacts with and deSUMOylates JAK2, promoting JAK2 accumulation in the cytoplasm for activation, which is critical for platinum-resistance in ovarian cancer.
CELL DEATH & DISEASE
(2021)
Article
Emergency Medicine
Kevin Kei Ching Hung, Timothy H. Rainer, Janice Hiu Hung Yeung, Catherine Cheung, Yuki Leung, Ling Yan Leung, Marc Chong, Hiu Fai Ho, Kwok Leung Tsui, Nai Kwong Cheung, Colin Graham
Summary: This study investigated the long-term health impacts of trauma among adult patients admitted to trauma centres in Hong Kong. The research found that the mortality rate remained consistently higher than expected, functional recovery was limited, and physical health status was worse up to 7 years post-injury.
EUROPEAN JOURNAL OF TRAUMA AND EMERGENCY SURGERY
(2022)
Review
Biochemistry & Molecular Biology
Huogang Wang, Mingo M. H. Yung, Hextan Y. S. Ngan, Karen K. L. Chan, David W. Chan
Summary: Metastasis, driven by tumor-associated macrophages (TAMs), is a key factor in most cancer deaths, with TAMs playing a crucial role in influencing tumor metastasis and treatment outcomes by polarizing metabolism patterns. Tumor cell-driven TAMs in the tumor microenvironment promote tumor metastasis and are associated with poor prognosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
David W. Chan, Wai-Yip Lam, Fushun Chen, Mingo M. H. Yung, Yau-Sang Chan, Wai-Sun Chan, Fangfang He, Stephanie S. Liu, Karen K. L. Chan, Benjamin Li, Hextan Y. S. Ngan
Summary: The study revealed a significant association of global DNA hypermethylation with poor prognosis and drug resistance in high-grade EOC, while demonstrating the potential of demethylating agents in cancer treatment.
CLINICAL EPIGENETICS
(2021)
Article
Cell Biology
Ming Yang, Michelle Grace Tsui, Jessica Kwan Wun Tsang, Rajesh Kumar Goit, Kwok-Ming Yao, Kwok-Fai So, Wai-Ching Lam, Amy Cheuk Yin Lo
Summary: This study reveals that both the GSH-GPx-4 and FSP1-CoQ(10)-NADH pathways inhibit retinal ferroptosis in RPE degeneration, suggesting potential treatment targets for RPE degenerative disorders.
CELL DEATH & DISEASE
(2022)
Review
Oncology
Daisy Wai-Ka Chan, Horace Cheuk-Wai Choi, Victor Ho-Fun Lee
Summary: This study conducted a systematic review and meta-analysis to investigate the treatment-related adverse events (trAEs) of combined epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI) and immune checkpoint inhibitor (ICI) in advanced non-small cell lung cancer (NSCLC). The results demonstrated a higher incidence of grade >= 3 trAEs in combination TKI and ICI, particularly in skin, gastrointestinal tract, and interstitial lung diseases. However, the interpretation of these results should be cautious due to the limited number of studies included in this meta-analysis.
Review
Biochemistry & Molecular Biology
Mingo M. H. Yung, Michelle K. Y. Siu, Hextan Y. S. Ngan, David W. Chan, Karen K. L. Chan
Summary: This article discusses a dual-targeted therapy for ovarian cancer, which involves the combination of AMPK activations with VEGF/PD-1 blockade. Additionally, ferroptosis initiating therapies and metabolic rewiring with immunotherapeutic approaches are proposed to have potential clinical significance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Emergency Medicine
Yan Ho Li, Janice Hiu Hung Yeung, Kevin Kei Ching Hung, Chun Yu Lai, Ling Yan Leung, Chi Hung Cheng, Nai Kwong Cheung, Colin A. Graham
Summary: This study analyzed the changes between AIS1998 and AIS2015, and their impact on injury severity scoring and survival prediction models. The results showed that AIS2015 had significant reductions in the classification of serious, severe, and critical categories, with an increase in the mild and moderate categories. Additionally, there were no significant differences in the number of cases, 30-day mortality, and discrimination of the prediction model between AIS2015 and AIS1998 at an ISS>15 threshold.
AMERICAN JOURNAL OF EMERGENCY MEDICINE
(2022)
Article
Emergency Medicine
Ronson Sze Long Lo, Le Elias Lyngholm, Mikkel Brabrand, Ling Yan Leung, Kevin Kei Ching Hung, Sune Laugesen, Stefan Posth, Tim Cooksley, Colin A. Graham, Christian H. Nickel
Summary: This study analyzed the performance of six clinical scoring systems in predicting 30-day all-cause mortality in two emergency departments. The results showed that these scoring systems had poor prediction ability, suggesting the need to supplement clinical scores with biochemical values or global markers of physiological reserve to improve performance.
HONG KONG JOURNAL OF EMERGENCY MEDICINE
(2023)
Article
Public, Environmental & Occupational Health
L. Yung, L. Y. Leung, K. H. Lee, S. Morrell, M. W. Fong, N. H. Y. Fung, K. L. Cheng, P. Kaewpreedee, Y. Li, B. J. Cowling, E. H. Y. Lau, D. S. C. Hui, C. A. Graham, H. -l. Yen
Summary: This study aims to monitor SARS-CoV-2 exposure risk among healthcare workers and identify risk factors associated with SARS-CoV-2 detection. Surface and air samples were collected longitudinally at an Emergency Department (ED) in Hong Kong, and viral RNA was detected using real-time reverse-transcription polymerase chain reaction. The results showed a low frequency of SARS-CoV-2 RNA detection, with crowding identified as the main risk factor. The study concludes that crowding in the ED may introduce SARS-CoV-2, but multiple factors contribute to low contamination.
JOURNAL OF HOSPITAL INFECTION
(2023)
Article
Medicine, Research & Experimental
Yang Xuan, Huogang Wang, Mingo M. H. Yung, Fushun Chen, Wai-Sun Chan, Yau-Sang Chan, Stephen K. W. Tsui, Hextan Y. S. Ngan, Karen K. L. Chan, David W. Chan
Summary: This study found that lipodynamic activity in malignant ascites derived from ovarian cancer is accelerated by upregulated expression of SCD1 and FADS2, leading to increased tumor aggressiveness. Inhibition of SCD1 and FADS2 can slow down tumor growth and increase sensitivity to chemotherapy drugs.
Article
Radiology, Nuclear Medicine & Medical Imaging
He An, Jose A. U. Perucho, Keith W. H. Chiu, Edward S. Hui, Mandy M. Y. Chu, Siew Fei Ngu, Hextan Y. S. Ngan, Elaine Y. P. Lee
Summary: This study investigated the association between functional tumor burden of peritoneal carcinomatosis derived from DWI and overall survival in patients with advanced ovarian carcinoma. The results showed that a high DWI-derived functional tumor burden was associated with decreased overall survival.
KOREAN JOURNAL OF RADIOLOGY
(2022)