Article
Cell Biology
Tian Xia, Di Chen, Xiaolong Liu, Huan Qi, Wen Wang, Huan Chen, Ting Ling, Wuxiyar Otkur, Chen-Song Zhang, Jongchan Kim, Sheng-Cai Lin, Hai-long Piao
Summary: In this study, it was found that intracellular MDK interacts with LKB1 and STRAD, leading to the disruption of the LKB1-STRAD-Mo25 complex. As a result, the activity of LKB1 is decreased, dampening the activation of AMPK. Additionally, MDK expression is significantly upregulated in liver, kidney, and breast cancers, and is inversely correlated with phosphorylated AMPK levels.
CELL DEATH & DISEASE
(2022)
Article
Chemistry, Multidisciplinary
Sheng Hong, Qian-Xiao Huang, Ping Ji, Xuan Pang, Yunxia Sun, Si-Xue Cheng, Xian-Zheng Zhang, Xuesi Chen
Summary: This study proposes a strategy to utilize the effects of Vadimezan-induced coagulation activation and hypoxia aggravation for targeted delivery and activation of a hypoxia-activated prodrug (HAP), thereby maximizing the therapeutic effect of Vadimezan. The results showed that this strategy achieved 80.0% suppression of tumor growth in a mouse tumor model, indicating its great potential in tumor treatment.
SCIENCE CHINA-CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Yu-jia Fang, Ming Wu, Hai-ni Chen, Tian-tian Wen, Jian-xin Lyu, Yao Shen
Summary: L-Carnosine has shown broad-spectrum anticancer activity against human glioma cells U87 and U251 by inhibiting glutamine synthetase expression, leading to decreased proliferation, migration, and invasion capabilities. This effect was independent of oxygen levels and may offer new treatment strategies for gliomas by targeting tumor metabolism.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Biochemistry & Molecular Biology
Daria Di Molfetta, Stefania Cannone, Maria Raffaella Greco, Rosa Caroppo, Francesca Piccapane, Tiago Miguel Amaral Carvalho, Concetta Altamura, Ilaria Saltarella, Diana Tavares Valente, Jean Francois Desaphy, Stephan J. J. Reshkin, Rosa Angela Cardone
Summary: Intracellular pH (pHi) regulation is crucial for the exocrine pancreas, and dysregulation of ion transporters, including bicarbonate transporters and NHE1, is observed in PDAC. The progression of PDAC is facilitated by the acidosis in Collagen-I rich ECM. Our study on organotypic cultures of normal human pancreatic cells (HPDE), parenchymal cancer cells (CPCs), and cancer stem cells (CSCs) reveals that the ECM composition and pHe fluctuations contribute to pHi dysregulation and the presence of NaHCO3 gradients similar to that in tumors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Xiuhui Shi, Min Wang, Yuqing Zhang, Xingjun Guo, Mingyang Liu, Zhijun Zhou, Yan Zhao, Ruizhi He, Yang Gao, Yuhui Liu, Shutao Pan, Min Zhou, Chunle Zhao, Taoyuan Yin, Xu Li, Hebin Wang, Jingxuan Yang, Feng Zhu, Min Li, Renyi Qin
Summary: High expression levels of alpha-SMA and hypoxia markers are associated with poor prognosis in pancreatic cancer patients. Mechanistically, hypoxia induces HGF expression and secretion in PSC via HIF-1 alpha, which then activates Met and suppresses pancreatic cancer cell sensitivity to EGFR inhibitors. The combination of EGFR inhibitor and Met inhibitor shows promise for pancreatic cancer treatment based on the demonstrated signaling axis between PSC and cancer cells.
Article
Pharmacology & Pharmacy
Ryszard Smolarczyk, Justyna Czapla, Magdalena Jarosz-Biej, Kyle Czerwinski, Tomasz Cichon
Summary: Tumor blood vessel formation is crucial for tumor expansion, and targeting tumor vessels specifically can be an effective anti-cancer treatment method.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Oncology
Aling Shen, Meizhu Wu, Liya Liu, Youqin Chen, Xiaoping Chen, Mingkai Zhuang, Qiurong Xie, Ying Cheng, Jiapeng Li, Zhiqing Shen, Lihui Wei, Jianfeng Chu, Thomas J. Sferra, Xiuli Zhang, Nanhui Xu, Li Li, Jun Peng, Fenglin Chen
Summary: NUFIP1 is overexpressed in CRC and correlates with disease progression and poor patient survival, potentially exerting oncogenic effects partly by altering cellular senescence. Ursolic acid (UA) shows potential to treat CRC by down-regulating NUFIP1.
FRONTIERS IN ONCOLOGY
(2021)
Article
Cell Biology
Dingan Luo, Youpeng Wang, Mao Zhang, Haoran Li, Deze Zhao, Hui Li, Xiaowu Chen, Cheng Jin, Bing Han
Summary: The Pringle maneuver (PM) used during hepatocellular carcinoma (HCC) resection can lead to tumor metastasis due to ischemia and hypoxia. This study discovered that high expression of suppressor of cytokine signaling 5 (SOCS5) significantly affected the prognosis of HCC patients undergoing long-time PM. The study also showed that SOCS5 promotes the expression of hypoxia-inducible factor 1 subunit alpha (HIF-1 alpha) protein, which is associated with higher hypoxia scores. Knockdown of SOCS5 inhibited HCC cell invasion and migration through the PI3K/Akt/mTOR/HIF-1 alpha signaling axis. This research highlights the potential of a SOCS5-specific inhibitor to control PM-induced tumor micrometastases during HCC resection.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Minxuan Yuan, Xiaogui Liang, Duantao Cao, Hongliang Wu, Suling Xiao, Hui Liang, Hang Li, Yingjin Huang, Hongyi Wei, Wenwen Peng, Xiaoxiang Fu
Summary: Dictamnine (DIC), a compound isolated from Clausena lansium, effectively inhibits the mycelial growth of B. dothidea and can be developed as a green fungicide for controlling pear ring rot. Transcriptome analysis showed that DIC significantly inhibits the synthesis of fungal cell wall and membrane components, leading to mycelial deformation and growth inhibition.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Mohsen Rashidi, Elham Mahmoudian, Sepideh Mirzaei, Seyadeh Narges Mazloomi, Ali Bazi, Hossein Azadeh, Mobina Mozaffari
Summary: Harmaline has anti-tumor effects on breast tumors by increasing tumor cells' sensitivity to doxorubicin, reducing the levels of proliferation and angiogenesis-related factors, and affecting the expression of immune factors and relevant genes.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Engineering, Biomedical
Yajun Xu, Jianlin Lv, Na Shen, Zhaohui Tang, Xuesi Chen
Summary: In this study, researchers constructed a self-activating nanoized plinabulin that can be selectively activated by intrinsic tumor hypoxia to disrupt tumor vessels and inhibit tumor growth. The nanoized plinabulin demonstrated selective distribution in tumors and showed stronger anti-tumor effects compared to traditional plinabulin.
Article
Chemistry, Multidisciplinary
Marie H. C. Boulet, Hannah R. Bolland, Ester M. Hammond, Adam C. Sedgwick
Summary: Platinum (IV) anticancer agents show potential to overcome limitations of commonly used Pt (II) chemotherapeutics and an improved understanding of their intracellular reduction is needed. Two fluorescence responsive oxaliplatin (IV) complexes, OxaliRes and OxaliNap, were synthesized and showed increased fluorescence emission intensity upon reduction by sodium ascorbate (NaAsc). Treatment with NaAsc increased fluorescence intensity in a dose-dependent manner in colorectal cancer cells. Hypoxia-induced reduction of OxPt (IV) complexes with <0.1% O-2 resulted in the greatest fluorescence signal and showed significant differences in toxicity compared to normoxia (21% O-2).
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Review
Immunology
Hongxia Jiang, Hanqiu Zhao, Mengzhe Zhang, Yuanzhou He, Xiaochen Li, Yongjian Xu, Xiansheng Liu
Summary: Exosomes are small vesicles that mediate intercellular communication by transferring various components. Hypoxia influences the content and effects of exosomes. Hypoxic exosomes derived from tumor cells lead to different biological effects depending on the recipient units. Understanding the characteristics of hypoxic exosomes provides new insight into the pathogenesis of hypoxia-related diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Yo Sep Hwang, Eun Sun Park, Byung Moo Oh, Tae Gi Uhm, Suk Ran Yoon, Jong-Lyul Park, Hee Jun Cho, Hee Gu Lee
Summary: ATAD2 overexpression is associated with poor survival and disease recurrence in breast cancer. miR-302 targets ATAD2 to inhibit cancer cell proliferation, migration, and invasion. This study suggests that targeting miR-302 could be a valuable therapeutic strategy for breast cancer.
Article
Biochemistry & Molecular Biology
Md. Abu Sufian, Sabina Zamanova, Ahmed M. Shabana, Brianna Kemp, Utpal K. Mondal, Claudiu T. Supuran, Marc A. Ilies
Summary: Carbonic anhydrase IX (CA IX) is an important enzyme involved in tumor survival, metastasis, and resistance to therapy in hypoxic tumor cells. The expression dynamics of CA IX in different oxygen conditions were investigated, along with its correlation with extracellular pH and cell viability. The study found that CA IX expression is retained in hypoxic cancer cells upon reoxygenation to preserve their proliferation ability. The sensitivity of cancer cells to CA IX inhibitors is higher in hypoxia and intermittent hypoxia compared to normoxia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Letter
Hematology
Killian Donovan, Athinoula Meli, Francesca Cendali, Kyung Chan Park, Rebecca Cardigan, Simon Stanworth, Stuart McKechnie, Angelo D'Alessandro, Peter A. Smethurst, Pawel Swietach
Article
Cardiac & Cardiovascular Systems
Abigail D. Wilson, Mark A. Richards, M. Kate Curtis, Mala Rohling, Stefania Monterisi, Aminah A. Loonat, Jack Miller, Vicky Ball, Andrew Lewis, Damian Tyler, Anna Moshnikova, Oleg A. Andreev, Yana K. Reshetnyak, Carolyn Carr, Pawel Swietach
Summary: In cardiomyocytes, the expression of pH regulators is fine-tuned to maintain a normal pHi and protect it from disturbances caused by acidic environments.
CARDIOVASCULAR RESEARCH
(2022)
Article
Medicine, General & Internal
Kathrin Schilling, Adrian L. Harris, Alex N. Halliday, Christopher J. Schofield, Helen Sheldon, Syed Haider, Fiona Larner
Summary: The study reveals differences in zinc isotope fractionation between in vitro experiments and in vivo breast cancer tissues, suggesting variations in zinc transporter levels or intracellular zinc storage mechanisms as the potential cause.
FRONTIERS IN MEDICINE
(2022)
Article
Oncology
Miriam Zatovicova, Ivana Kajanova, Monika Barathova, Martina Takacova, Martina Labudova, Lucia Csaderova, Lenka Jelenska, Eliska Svastova, Silvia Pastorekova, Adrian L. Harris, Jaromir Pastorek
Summary: Hypoxia in the tumor microenvironment is a major factor in cancer progression, and low levels of oxygen may indicate treatment failure. Carbonic anhydrase IX (CA IX) is a precise target in hypoxic tumors, and its presence contributes to the failure of standard therapy. Humanized antibodies against CA IX show promise as suitable therapies for hypoxic tumors, with the ability to modulate the tumor microenvironment, induce an immune response, and block metastasis formation.
CANCER & METABOLISM
(2022)
Article
Oncology
Hannah Bolland, Eric Vancauwenberghe, Pamela Collier, Anna M. M. Grabowska, Alan McIntyre, Adrian L. Harris, Christopher Paul Carrol, Alison A. Ritchie, Philip A. Clarke
Summary: Regions of low oxygen are commonly found in breast tumors, especially in the aggressive triple negative subtype. Metastasis is the leading cause of death in breast cancer patients. The expression of Na+ driven bicarbonate transporters (NDBTs) is increased in hypoxic breast cancer, and targeting hypoxia-induced NDBTs can reduce tumor migration, invasion, and metastasis.
Article
Cell Biology
Christos E. Zois, Anne M. Hendriks, Syed Haider, Elisabete Pires, Esther Bridges, Dimitra Kalamida, Dimitrios Voukantsis, B. Christoffer Lagerholm, Rudolf S. N. Fehrmann, Wilfred F. A. den Dunnen, Andrei I. Tarasov, Otto Baba, John Morris, Francesca M. Buffa, James S. O. McCullagh, Mathilde Jalving, Adrian L. Harris
Summary: This study reveals the significant role of glycogen metabolism in glioblastoma (GBM) cancer. Inhibition of glycogen degradation sensitizes GBM cells to high-dose ionising radiation (IR), suggesting that PYGL may serve as a potential novel target for GBM treatment.
CELL DEATH & DISEASE
(2022)
Editorial Material
Oncology
Adrian L. Harris
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Tong Yu, Archana Chandrabhan Jadhav, Jiabao B. Xu, Adrian L. L. Harris, Venugopal Nair, Wei E. E. Huang
Summary: Understanding the development of cancer resistance to therapies is crucial. Newcastle disease virus (NDV) is a promising oncolytic agent, but some colon cancer cells show resistance to NDV reinfection. By using Raman spectroscopic and stable isotopic techniques, we found that the resistant cells slow down their replication and divert energy to protein and lipid synthesis. Understanding metabolic reprogramming could aid in developing precision cancer treatments that target resistant cells at the single-cell level.
Article
Oncology
Simon R. Lord, Adrian L. Harris
Summary: Over the past 15 years, there has been extensive interest in repurposing the diabetes drug metformin as a cancer treatment. However, despite numerous large clinical trials in various tumor types, the results have been disappointing. This article summarizes the initial interest in metformin's potential in oncology, the current clinical program, and the lessons learned from this experience regarding further investigation of metformin in cancer.
BRITISH JOURNAL OF CANCER
(2023)
Article
Cell Biology
Johanna Michl, Stefania Monterisi, Bobby White, Wiktoria Blaszczak, Alzbeta Hulikova, Gulnar Abdullayeva, Esther Bridges, Zinan Yin, Walter F. Bodmer, Pawel Swietach
Summary: Acidic environments reduce the intracellular pH of most cells, but cancers maintain an alkaline cytoplasm. We identified AE2 as a regulator of resting pHi and found that cells adapt to chronic acidosis by degrading AE2 protein. Inhibition of lysosomal degradation of AE2 may be a potential therapeutic target for maintaining a conducive pH in tumors.
Article
Oncology
Soumya Ghose, Sanghee Cho, Fiona Ginty, Elizabeth McDonough, Cynthia Davis, Zhanpan Zhang, Jhimli Mitra, Adrian L. Harris, Aye Aye Thike, Puay Hoon Tan, Yesim Gokmen-Polar, Sunil S. Badve
Summary: The authors developed a deep learning classification network to predict breast cancer events (BCEs) in patients with ductal carcinoma in situ (DCIS), providing early and accurate predictions for personalized therapy and avoiding over-treatment of low-risk patients.
Editorial Material
Oncology
Nicole D. D. Machado, Lisa C. C. Heather, Adrian L. L. Harris, Geoff S. S. Higgins
Summary: The disappointing termination of clinical trials with potent complex I inhibitors, such as IACS-010759, has raised doubts about the justification for oxidative phosphorylation inhibitors and mitochondrial targeting strategies. Analyzing the potency, tissue selectivity, and toxicity of these agents can provide insights into the lessons learned from this failure and identify new opportunities.
BRITISH JOURNAL OF CANCER
(2023)
Review
Physiology
Bobby White, Pawel Swietach
Summary: Acidosis is a chemical feature of the tumor microenvironment that affects cellular pH homeostasis. Acid-base transporters of the SLC family play a critical role in removing lactate/H+ products and maintaining alkaline cytoplasm. Mutations in these transporters may impact cancer development, and targeting acid-base transport can be validated through genomic analysis and phenotypic outcomes.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2023)
Review
Oncology
Pawel Swietach, Ebbe Boedtkjer, Stine Falsig Pedersen
Summary: Changes in proton concentration and sensing play a crucial role in cancer progression by influencing protein activity and pH balance. The acidic microenvironment of tumors, caused by metabolic changes, affects various aspects of tumor biology and accelerates disease progression. Targeting acid-base disturbances in cancer presents potential therapeutic opportunities.
NATURE REVIEWS CANCER
(2023)
Article
Hematology
Julija Rabcuka, Slawomir Blonski, Athinoula Meli, Samuel Sowemimo-Coker, Damian Zaremba, Daniel Stephenson, Monika Dzieciatkowska, David Nerguizian, Rebecca Cardigan, Piotr M. Korczyk, Peter A. Smethurst, Angelo D'Alessandro, Pawel Swietach
Summary: Stored red blood cells undergo biochemical and morphological changes that affect oxygen unloading. Hypoxic storage preserves gas-handling properties and improves the quality of blood products.