Article
Oncology
Sara J. Hamis, Yury Kapelyukh, Aileen McLaren, Colin J. Henderson, C. Roland Wolf, Mark A. J. Chaplain
Summary: The study developed a mechanistic mathematical model to describe the synergistic action of dabrafenib and trametinib on ERK activity in BRAFV600E-mutant melanoma cells, elucidating the molecular mechanism underlying vertical inhibition of the BRAF-MEK-ERK cascade.
BRITISH JOURNAL OF CANCER
(2021)
Article
Oncology
Aayoung Hong, Marco Piva, Sixue Liu, Willy Hugo, Shirley H. Lomeli, Vincent Zoete, Christopher E. Randolph, Zhentao Yang, Yan Wang, Jordan J. Lee, Skylar J. Lo, Lu Sun, Agustin Vega-Crespo, Alejandro J. Garcia, David B. Shackelford, Steven M. Dubinett, Philip O. Scumpia, Stephanie D. Byrum, Alan J. Tackett, Timothy R. Donahue, Olivier Michielin, Sheri L. Holmen, Antoni Ribas, Gatien Moriceau, Roger S. Lo
Summary: Combining type II RAF inhibitor with MEK inhibitor effectively prevents and overcomes acquired resistance in cancers with specific mutations, while also expanding memory and activated CD8(+) T cells. This combination therapy shows potential in broad cancer indications and may be further enhanced by exploring mechanisms of MAPK protein interactions and preserving tumor-infiltrating T cells.
Article
Oncology
Angela Duff, Llona Kavege, Jocelyn Baquier, Tang Hu
Summary: LY294002, initially reported as a selective inhibitor of PI3K-Akt, was found to inhibit other molecules as well. The study showed that LY294002 significantly inhibits proliferation and induces cluster formation in MV4-11, TF-1a, and Hep-G2 cells. Furthermore, LY294002 repressed the activation of MEK and ERK signal molecules in all cells, suggesting a potential direct inhibition mechanism.
Article
Oncology
Rahim Ullah, Qing Yin, Aidan H. Snell, Lixin Wan
Summary: The RAF-MEK-ERK signaling cascade is a well-characterized MAPK pathway that plays a critical role in cell proliferation and survival. Genetic alterations in this pathway are highly prevalent in human cancers and can lead to uncontrolled cell growth and tumor formation. The crosstalk between the RAF-MEK-ERK axis and other signaling pathways further enhances its proliferative potential in human cancers.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Oncology
Ying Zhang, Qian Lu, Nan Li, Ming Xu, Tatsuo Miyamoto, Jing Liu
Summary: Sulforaphane (SFN), a natural compound derived from broccoli, has been found to significantly inhibit migration and invasion of breast cancer cells by affecting cytoskeleton formation. SFN can also directly bind to RAF family proteins and inhibit phosphorylation of the signaling pathway. These findings suggest that SFN has the potential to be used as a therapeutic drug to inhibit breast cancer cell metastasis.
Article
Biochemistry & Molecular Biology
Franziska Leichtle, Annika C. Betzler, Carlotta Eizenberger, Kristina Lesakova, Jasmin Ezic, Robert Drees, Jens Greve, Patrick J. Schuler, Simon Laban, Thomas K. Hoffmann, Nils Cordes, Marialuisa Lavitrano, Emanuela Grassilli, Cornelia Brunner
Summary: The expression of BTK in head and neck squamous cell carcinoma is associated with metastasis and malignancy. Inhibiting BTK activity could be a promising treatment option.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Xishan Chen, Renba Liang, Huan Lin, Kaihua Chen, Li Chen, Ge Tian, Xiaodong Zhu
Summary: Downregulation of CD166 inhibited CSC-related genes and decreased pEGFR and pERK expression in vitro and in vivo. The sphere formation and tumorigenesis ability of CD166-shRNA cells were significantly reduced. Additionally, EGF-stimulated CD166-shRNA cells showed an increase in CSC-like traits by activating the EGFR/ERK1/2 signaling pathway.
Review
Oncology
Renee Barbosa, Lucila A. Acevedo, Ronen Marmorstein
Summary: The RAS-RAF-MEK-ERK pathway is crucial for cell proliferation, differentiation, and survival, with mutations in upstream proteins RAS and RAF contributing to many human cancers and nearly all cutaneous melanomas. Targeting terminal kinases in the MAPK cascade has shown promise in overcoming drug resistance and improving treatment options for patients with MAPK-aberrant cancers.
MOLECULAR CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Wei Liu, Lei Wang, Jiajia Zhang, Kun Cheng, Wenming Zheng, Zhenling Ma
Summary: Ovarian cancer has a lower incidence rate compared to other gynecological tumor types, but it has the second-highest death rate. CCL2, a multifunctional factor associated with cancer progression, was found to promote proliferation and metastasis of ovarian cancer cells when overexpressed. Knocking down CCL2 inhibited ovarian cancer cell proliferation, migration, and invasion. The study showed that MAP3K19 is the key target through which CCL2 regulates ovarian cancer progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Xin Li, Shuang Zhao, Xiaohui Bian, Lining Zhang, Lixia Lu, Shiyao Pei, Liang Dong, Wensheng Shi, Lingjuan Huang, Xiyuan Zhang, Mingliang Chen, Xiang Chen, Mingzhu Yin
Summary: Our study investigates the changes in tumor microenvironment (TME) between primary and recurrent cutaneous squamous cell carcinoma (cSCC) using single-cell RNA sequencing (scRNA-seq). We identified an immunosuppressed microenvironment in recurrent cSCC, with T cell exclusion and enrichment of SPP1+ tumor-associated macrophages (TAMs). CD8+ T cells showed exhaustion and low inflammatory features, while SPP1+ TAMs displayed pro-tumor characteristics. Different subgroups of SPP1+ TAMs exhibited distinct functions. A subset of tumor-specific keratinocytes (TSKs) showed significant epithelial-mesenchymal transition (EMT) features, possibly due to their interaction with IL7R+ cancer-associated fibroblasts (CAFs). We also found that the growth factor/cytokine Midkine (MDK) played a role in different cell-cell interactions in cSCC with different staging.
Article
Oncology
Da Wang, Fei Xiong, Guanhua Wu, Wenzheng Liu, Bing Wang, Yongjun Chen
Summary: The study found that in cholangiocarcinoma, miR-155-5p targets the 3' UTR of SOX1, activating the RAF/MEK/ERK pathway and promoting cancer progression.
CANCER CELL INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Masanori Hijioka, Yusuke Ikemoto, Kosuke Fukao, Takeshi Inoue, Tatsuki Kobayakawa, Kaneyasu Nishimura, Kazuyuki Takata, Kiyokazu Agata, Yoshihisa Kitamura
Summary: The study revealed the involvement of the MEK/ERK pathway in the regeneration of dopaminergic neurons in planarians, with MEK inhibitors affecting head region morphogenesis and reducing the number of dopaminergic neurons.
NEUROCHEMICAL RESEARCH
(2022)
Article
Environmental Sciences
Qing Zhou, Peiyu Jin, Jieyu Liu, Sihao Li, Weijue Liu, Shuhua Xi
Summary: Arsenic is strongly associated with bladder cancer, and understanding its mechanisms and preventive interventions is crucial for reducing the incidence and mortality of the disease. Chronic exposure to arsenic can induce EMT and increase CSC marker CD44 levels, while IL-8 promotes EMT and upregulates CD44 expression through multiple signaling pathways.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Cell Biology
Yichi Xu, Xin Chen, Shuya Pan, Zhi-wei Wang, Xueqiong Zhu
Summary: TM7SF2 plays a crucial role in promoting cell proliferation and metastasis, inhibiting cell apoptosis, preventing G0/G1 phase arrest, and participating in tumorigenesis and progression through the C-Raf/ERK pathway in cervical cancer. The overexpression of TM7SF2 enhances xenograft tumor growth in vivo, indicating its potential as a therapeutic target for cervical cancer treatment in the future.
CELL DEATH DISCOVERY
(2021)
Article
Orthopedics
Xiangchao Meng, Wei Zhang, Zhuocheng Lyu, Teng Long, You Wang
Summary: This study demonstrates that zinc oxide nanoparticles (ZnO NPs) can attenuate inflammation induced by polymer wear particles by regulating the MEK-ERK-COX-2 axis, thus preventing inflammatory osteolysis in bone tissue.
JOURNAL OF ORTHOPAEDIC TRANSLATION
(2022)
Review
Biochemistry & Molecular Biology
Masoud Najafi, Shima Tavakol, Ali Zarrabi, Milad Ashrafizadeh
Summary: Chemotherapy is an important treatment for cancer, but the resistance of cancer cells reduces its effectiveness. Quercetin, a flavonoid compound with high anti-tumour activity, can be used with cisplatin to enhance the efficacy of chemotherapy and reduce its side effects.
ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY
(2022)
Review
Immunology
Keywan Mortezaee, Jamal Majidpoor
Summary: Tumor-associated macrophages (TAMs) are immune cells that infiltrate tumor areas and have intense interactions with other cells. The metabolic abnormalities in tumors can affect the polarization of macrophages towards pro-tumor or anti-tumor phenotypes. Adjusting the metabolic systems of macrophages can be an effective tool in cancer therapy.
INTERNATIONAL REVIEWS OF IMMUNOLOGY
(2023)
Review
Cell Biology
Xiao-yu Wu, Wen-Wen Xu, Xiang-kun Huan, Guan-nan Wu, Gang Li, Yu-Hong Zhou, Masoud Najafi
Summary: Resistance of cancer cells to anti-tumour agents is a major challenge in cancer treatment. Metformin, an antidiabetic drug, can enhance cell death mechanisms and play a key role in inducing cell death, thereby increasing the therapeutic efficiency of anti-cancer therapy.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Masoud Moslehi, Sepideh Rezaei, Pourya Talebzadeh, Mohammad Javed Ansari, Mohammed Abed Jawad, Abduladheem Turki Jalil, Nima Rastegar-Pouyani, Emad Jafarzadeh, Shahram Taeb, Masoud Najafi
Summary: The incidence of cancer is increasing globally. The long-term adverse effects of cancer therapy and tumor resistance to anticancer agents are major concerns. Apigenin, a plant-derived molecule, has potential as an adjuvant for chemoprevention and overcoming malignancy resistance to cancer therapy. It has promising anti-tumor effects and may reduce genomic instability and risks of second malignancies in normal tissues, as well as improve the efficacy of anticancer modalities.
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
(2023)
Review
Cell Biology
Keywan Mortezaee, Jamal Majidpoor
Summary: The low frequency of durable responses in patients treated with immune checkpoint inhibitors (ICIs) requires additional strategies to enhance immune responses against cancer. Transforming growth factor-beta (TGF-beta) is a cytokine often expressed in tumors and promotes an immunosuppressive tumor microenvironment (TME). TGF-beta also influences the efficacy of anti-PD-1/PD-L1 therapy. Combining TGF-beta inhibitors with anti-PD(L)1 has shown promising results, and clinical trials are currently underway to investigate the use of agents with bifunctional capacity and fusion proteins to reinvigorate immune responses against advanced stage cancers, particularly those with an immunologically cold ecosystem.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2023)
Review
Immunology
Arian Charehjoo, Jamal Majidpoor, Keywan Mortezaee
Summary: Metabolic alterations occur commonly in tumor cells to adapt energetic sources for proliferation, survival, and resistance. IDO1 is an enzyme that degrades tryptophan and its upregulation in cancer stroma impacts immune tolerance and cancer evasion. IDO1 inhibitors combined with immune checkpoint inhibitors show promise in treating advanced solid tumors and overcoming ICI therapy bypass.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Immunology
Keywan Mortezaee
Summary: B7x is a co-inhibitory molecule highly expressed in non-inflamed cancers, contributing to cancer progression and poor outcomes. It hampers peripheral immune responses and promotes immunosuppressive cells and regulatory T cells in cancer. Evaluation of B7x in sera is a potential biomarker for cancer patient response. B7x overexpression is involved in tumor resistance to immune checkpoint inhibitor therapy, but anti-B7x treatment can reinvigorate exhausted T cells and complement conventional ICI therapy. The development of bispecific antibodies against B7x and other regulatory molecules is an advance in the field.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Instruments & Instrumentation
Sajad Najafi, Jamal Majidpoor, Keywan Mortezaee
Summary: Extracellular vesicles (EVs) are membrane-bound organelles released from eukaryotic cells that can be used as biomarkers for human diseases. EVs have favorable features as ideal drug carriers and vaccines for diseases including cancer.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2023)
Review
Multidisciplinary Sciences
Keywan Mortezaee, Jamal Majidpoor
Summary: This review discusses the impact of mono or combination therapy of immune checkpoint inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC) patients, comparing clinical outcomes and safety. Cancer subtype, tumor mutational burden (TMB), programmed death-ligand 1 (PD-L1) expression state and T cell infiltration (TIL) density are considered for interpretations. Besides, current progresses in the field of immunotherapy are discussed.
Article
Medicine, Research & Experimental
Sajad Najafi, Keywan Mortezaee
Summary: Traditionally, vaccines have played a crucial role in eradicating infectious diseases and saving millions of lives. However, the development of anticancer vaccines faces challenges and requires further optimization. Dendritic cells, as the most potent antigen presenting cells, have been used in tumor immunotherapies but their efficacy needs improvement.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Pathology
Sasan Parvini, Jamal Majidpoor, Keywan Mortezaee
Summary: This review focuses on the impact of PD-L1 on combo nivolumab-ipilimumab therapy in advanced solid cancer patients, indicating that patient responses can be affected by different levels of PD-L1 expression. Variations in responses are observed among different cancer types or doses of immunotherapy drugs. Therefore, relying solely on PD-L1 as a biomarker may not be reliable for predicting the clinical efficacy of combo nivolumab-ipilimumab. Other biomarkers or a combination of PD-L1 with other factors should be considered for predicting patient responses.
PATHOLOGY RESEARCH AND PRACTICE
(2023)
Review
Oncology
Keywan Mortezaee, Jamal Majidpoor
Summary: Extracellular vesicles (EVs), particularly exosomes, play a crucial role in the communication and signal transmission between tumor cells and the tumor microenvironment (TME). Hypoxia, a characteristic of TME, stimulates tumor cells to release more EVs, which transfer biological information to promote hypoxia and hypoxia inducible factor (HIF) functionality. The EVs secreted under hypoxic conditions carry pro-tumorigenic factors that contribute to various tumor-related processes including cancer cell proliferation and survival, immune escape, angiogenesis, invasion, metastasis, and therapy resistance. This review focuses on the interplay between hypoxia and EVs, particularly exosomes, and their impact on key hallmarks of cancer.
Article
Oncology
Saeed Rezapoor, Amirhossein Ahmadi, Hojatollah Shahbazian, Mohsen Cheki
Summary: This study evaluated the radioprotective ability of glucosamine against radiation-induced genotoxicity and cytotoxicity in human lymphocytes. The results showed that glucosamine reduced the frequency of micronuclei and prevented lymphocyte apoptosis caused by radiation. Additionally, glucosamine reduced the production of reactive oxygen species in irradiated lymphocytes.
Article
Biochemistry & Molecular Biology
Ehsan Khodamoradi, Shima Afrashi, Karim Khoshgard, Farshid Fathi, Soodeh Shahasavari, Rasool Azmoonfar, Masoud Najafi
Summary: This study aimed to evaluate the effects of simultaneous exposure to Wi-Fi waves and gamma-ray on DNA in peripheral blood lymphocytes. The results showed that simultaneous exposure to Wi-Fi waves and gamma-ray can increase the number of double-strand breaks in DNA in peripheral blood lymphocytes within 72 hours after technetium injection.
BIOCHEMISTRY AND BIOPHYSICS REPORTS
(2022)
Correction
Engineering, Biomedical
Pooyan Makvandi, Milad Ashrafizadeh, Matineh Ghomi, Masoud Najafi, Hamid Heydari Sheikh Hossein, Ali Zarrabi, Virgilio Mattoli, Rajender S. Varma
PROGRESS IN BIOMATERIALS
(2022)