831,989 results match your criteria cancer cells

Rational design of synthetically tractable HDAC6/HSP90 dual inhibitors to destroy immune-suppressive tumor microenvironment.

J Adv Res 2022 Jun 22. Epub 2022 Jun 22.

School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 110031, Taiwan; TMU Research Center of Drug Discovery, Taipei Medical University, Taipei 110031, Taiwan. Electronic address:

Introduction: The tumor microenvironment is mainly flooded with immunosuppressive cells and inhibitory cytokines, resulting in the inability of effective immune cells to infiltrate and recognize tumors and even the loss of anti-cancer ability.

Objectives: We propose a novel HDAC6/HSP90 dual inhibitory strategy as well as a chemoimmunotherapeutic agent that does not only kill tumor cells but also destroys the tumor microenvironment and enhances anti-cancer immunity.

Methods: A hybrid scaffold construction approach was leveraged to furnish a series of rationally designed resorcinol-based hydroxamates as dual selective HDAC6/HSP90 inhibitors. Read More

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Ezrin gone rogue in cancer progression and metastasis: An enticing therapeutic target.

Biochim Biophys Acta Rev Cancer 2022 Jun 22:188753. Epub 2022 Jun 22.

Cancer Biology Division, National Centre for Cell Science, Ganeshkhind Road, Pune, Maharashtra 411007, India. Electronic address:

Cancer metastasis is the primary cause of morbidity and mortality in cancer as it remains the most complicated, devastating, and enigmatic aspect of cancer. Several decades of extensive research have identified several key players closely associated with metastasis. Among these players, cytoskeletal linker Ezrin (the founding member of the ERM (Ezrin-Radixin-Moesin)family) was identified as a critical promoter of metastasis in pediatric cancers in the early 21st century. Read More

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Targeting inflamed and non-inflamed melanomas: biological background and clinical challenges.

Semin Cancer Biol 2022 Jun 22. Epub 2022 Jun 22.

University of Perugia, Department of Surgery and Medicine, Unit of Medical Oncology, Perugia, Italy. Electronic address:

Immune checkpoint inhibitors (ICIs) have demonstrated impressive antitumor activity in patients with advanced and early stage melanoma, thus improving long-term survival outcomes. However, most patients derive limited benefit from immunotherapy, due to the development of primary, adaptive, or acquired resistance mechanisms. Immunotherapy resistance is a complex phenomenon that depends on genetic and epigenetic mechanisms which, in turn, drive the interplay between cancer cells and the tumor microenvironment (TME). Read More

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Systematic multi-omics reveals the overactivation of T cell receptor signaling in immune system following bisphenol A exposure.

Environ Pollut 2022 Jun 22:119590. Epub 2022 Jun 22.

Department of Animal Science & Technology and BET Research Institute, Chung-Ang University, Anseong, Gyeonggi-do 17546, South Korea. Electronic address:

Bisphenol A (BPA) is pervasive in the environment, and exposure to BPA may increase the incidence of noncommunicable diseases like autoimmune diseases and cancer. Although BPA causes immunological problems at the cellular level, no system-level research has been conducted on this. Hence, in this study, we aimed to gain a better understanding of the biological response to BPA exposure and its association with immunological disorders. Read More

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Subcellular dynamics and functional activity of the cleaved intracellular domain of the Na channel β1 subunit.

J Biol Chem 2022 Jun 22:102174. Epub 2022 Jun 22.

Department of Biology, University of York, Heslington, York, YO10 5DD, UK; York Biomedical Research Institute, University of York, Heslington, York, YO10 5DD, UK. Electronic address:

The voltage-gated Na channel β1 subunit, encoded by SCN1B, regulates cell surface expression and gating of α subunits and participates in cell adhesion. β1 is cleaved by α/β and γ-secretases, releasing an extracellular domain and intracellular domain (ICD), respectively. Abnormal SCN1B expression/function is linked to pathologies including epilepsy, cardiac arrhythmia, and cancer. Read More

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DEAD Box 1 (DDX1) protein binds to and protects cytoplasmic stress response mRNAs in cells exposed to oxidative stress.

J Biol Chem 2022 Jun 22:102180. Epub 2022 Jun 22.

Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, T6G 1Z2, Canada. Electronic address:

The Integrated Stress Response (ISR) is a network of highly-orchestrated pathways activated when cells are exposed to various types of environmental stressors. While global repression of translation is a well-recognized hallmark of the ISR, less is known about the regulation of mRNA stability during stress. DEAD box proteins are a family of RNA unwinding/remodeling enzymes involved in every aspect of RNA metabolism. Read More

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Characterizing unexpected interactions of a glutamine transporter inhibitor with members of the SLC1A transporter family.

J Biol Chem 2022 Jun 22:102178. Epub 2022 Jun 22.

School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, NSW, Australia. Electronic address:

The Solute Carrier 1A (SLC1A) family comprises a group of membrane proteins that act as dual-function amino acid transporters and chloride channels and includes the alanine serine cysteine transporters (ASCTs) as well as the excitatory amino acid transporters (EAATs). ASCT2 is regarded as a promising target for cancer therapy, as it can transport glutamine and other neutral amino acids into cells and is upregulated in a range of solid tumors. The compound L-γ-glutamyl-p-nitroanilide (GPNA) is widely used in studies probing the role of ASCT2 in cancer biology; however, the mechanism by which GPNA inhibits ASCT2 is not entirely clear. Read More

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CLDN6 inhibits breast cancer cell malignant behavior by suppressing ERK signaling.

Cell Signal 2022 Jun 22:110393. Epub 2022 Jun 22.

The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, 126 Xinmin Avenue, Changchun, Jilin 130021, People's Republic of China. Electronic address:

Claudin 6 (CLDN6) is an important component of tight junctions. Through the PDZ binding motif, CLDN6 binds to a variety of signaling proteins that contain the PDZ domain to regulate different signaling pathways, and plays an important role in the occurrence and development of tumors. Our previous work showed that CLDN6 was expressed at low levels in breast cancer cells, and overexpression of CLDN6 inhibited breast cancer cell proliferation, migration and invasion. Read More

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Vav1 accelerates Ras-driven lung cancer and modulates its tumor microenvironment.

Cell Signal 2022 Jun 22:110395. Epub 2022 Jun 22.

Departement of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Hadassah Medical School - Hebrew University, Jerusalem, Israel. Electronic address:

The potential impact of Vav1 on human cancer was only recently acknowledged, as it is detected as a mutant or an overexpressed gene in various cancers, including lung cancer. Vav1, which is normally and exclusively expressed in the hematopoietic system functions as a specific GDP/GTP nucleotide exchange factor (GEF), strictly regulated by tyrosine phosphorylation. To investigate whether Vav1 plays a causative or facilitating role in-vivo in lung cancer development and to examine whether it co-operates with other oncogenes, such as mutant K-Ras, we generated novel mouse strains that express: Vav1 or K-Ras in type II pneumocytes, as well as a transgenic mouse line that expresses both Vav1 and K-Ras in these cells. Read More

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MCPIP1 promotes cell proliferation, migration and angiogenesis of glioma via VEGFA-mediated ERK pathway.

Exp Cell Res 2022 Jun 22:113267. Epub 2022 Jun 22.

Department of Anatomy, School of Basic Medicine, Anhui Medical University, Hefei, Anhui, 230032, China. Electronic address:

Glioma is the most common primary malignant intracranial tumor in the population, and is often associated with abundant angiogenesis. However, how angiogenesis is regulated during glioma progression is still poorly understood. Data mining of cancer patient database shows that MCPIP1 is positively correlated with VEGFA expression and negatively with survival. Read More

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CAFs-secreted exosomal cricN4BP2L2 promoted colorectal cancer stemness and chemoresistance by interacting with EIF4A3.

Exp Cell Res 2022 Jun 22:113266. Epub 2022 Jun 22.

Department of Gynecology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, PR China. Electronic address:

Cancer-associated fibroblasts secreted exosomes (CAFs-exo) are important for tumor carcinogenesis and chemoresistance, but its underlying mechanism in colorectal cancer (CRC) has not yet been clarified. In this study, we investigated the regulatory mechanism of CAFs-exo cricN4BP2L2 on the proliferation, apoptosis, stemness and chemoresistance of LoVo cells. We found that CAFs-exo promoted the oxaliplatin resistance and stemness of LoVo cells, while inhibited the LoVo cell apoptosis. Read More

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A new class of half-sandwich ruthenium complexes containing Biginelli hybrids: anticancer and anti-SARS-CoV-2 activities.

Chem Biol Interact 2022 Jun 22:110025. Epub 2022 Jun 22.

Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Aljouf, Sakaka, 72341, Saudi Arabia.

In order to discover new dual-active agents, a series of novel Biginelli hybrids (tetrahydropyrimidines) and their ruthenium(II) complexes were synthesized. Newly synthesized compounds were characterized by IR, NMR, and X-ray techniques and investigated for their cytotoxic effect on human cancer cell lines HeLa, LS174, A549, A375, K562 and normal fibroblasts (MRC-5). For further examination of the cytotoxic mechanisms of novel complexes, two of them were chosen for analyzing their effects on the distribution of HeLa cells in the cell cycle phases. Read More

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Mesenchymal stromal cells cultured in physiological conditions sustain citrate secretion with glutamate anaplerosis.

Mol Metab 2022 Jun 22:101532. Epub 2022 Jun 22.

Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, Glasgow, G61 1QH, UK. Electronic address:

Bone marrow mesenchymal stromal cells (MSCs) have immunomodulatory and regenerative potential. However, culture conditions govern their metabolic processes and therapeutic efficacy. Here we show that culturing donor-derived MSCs in Plasmax™, a physiological medium with the concentrations of nutrients found in human plasma, supports their proliferation and stemness, and prevents the nutritional stress induced by the conventional medium DMEM. Read More

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Uncovering potential interventions for pancreatic cancer patients via mathematical modeling.

J Theor Biol 2022 Jun 22:111197. Epub 2022 Jun 22.

Department of Mathematics, University of Kentucky, Lexington, Kentucky, USA. Electronic address:

Pancreatic Ductal Adenocarcinoma (PDAC) is widely known for its poor prognosis because it is often diagnosed when the cancer is in a later stage. We built a Boolean model to analyze the microenvironment of pancreatic cancer in order to better understand the interplay between pancreatic cancer, stellate cells, and their signaling cytokines. Specifically, we have used our model to study the impact of inducing four common mutations: KRAS, TP53, SMAD4, and CDKN2A. Read More

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35 years of discussions with Prof. Maeda on the EPR effect and future directions.

J Control Release 2022 Jun 22. Epub 2022 Jun 22.

Former President of Japan Society of Drug Delivery System, 5-3-13, Otsuka, Bunkyo-ku, Tokyo, 112-0012, Japan, Visiting Scientist, Department of Immune Medicine, National Cancer Center Research Institute 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. Electronic address:

In May 2021, 35 years after first announcing the enhanced permeability and retention (EPR) effect, Dr. Maeda passed away. As a theoretical pillar of high molecular weight drug delivery systems (DDS) with high biocompatibility, the EPR effect has been proven worldwide in experimental mouse models. Read More

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Organic quantum dots: An ultrasmall nanoplatform for cancer theranostics.

J Control Release 2022 Jun 22. Epub 2022 Jun 22.

Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKMs NMIMS, V. L. Mehta Road, Vile Parle (W), Mumbai, Maharashtra 400056, India. Electronic address:

Tumours are the second leading cause of death globally, generating alterations in biological interactions and, as a result, malfunctioning of crucial genetic traits. Technological advancements have made it possible to identify tumours at the cellular level, making transcriptional gene variations and other genetic variables more easily investigated. Standard chemotherapy is seen as a non-specific treatment that has the potential to destroy healthy cells while also causing systemic toxicity in individuals. Read More

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Organoids as a Model System for Studying Notch Signaling in Intestinal Epithelial Homeostasis and Intestinal Cancer.

Am J Pathol 2022 Jun 22. Epub 2022 Jun 22.

Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio. Electronic address:

Organoid culture is an approach that allows three-dimensional growth for stem cells to self-organize and develop multicellular structures. Intestinal organoids have been widely used to study cellular or molecular processes in stem cell and cancer research. These cultures possess the ability to maintain cellular complexity as well as recapitulate many properties of the human intestinal epithelium, thereby providing an ideal in vitro model to investigate cellular and molecular signaling pathways. Read More

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The Role of Extracellular Vesicles in Liver Pathogenesis.

Am J Pathol 2022 Jun 22. Epub 2022 Jun 22.

Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA, 70112. Electronic address:

Extracellular vesicles are generated by cells in the form of exosomes, microvesicles and apoptotic bodies. They can be taken by neighboring cells and their contents can have functional impact on cells that engulf them. As the mediators of intercellular communication, extracellular vesicles can play important roles in both physiological and pathological contexts. Read More

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Oncostatic activities of melatonin: Roles in cell cycle, apoptosis, and autophagy.

Biochimie 2022 Jun 22. Epub 2022 Jun 22.

Metabolic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran; Department of Clinical Biochemistry, Faculty of Medicine, Golestan University of Medical Sciences, Babol, Iran. Electronic address:

Melatonin, the major secretory product of the pineal gland, not only regulates circadian rhythms, mood, and sleep but also has actions in neoplastic processes which are being intensively investigated. Melatonin is a promising molecule which considered a differentiating agent in some cancer cells at both physiological and pharmacological concentrations. It can also reduce invasive and metastatic status through receptors MT1 and MT2 cytosolic binding sites, including calmodulin and quinone reductase II enzyme, and nuclear receptors related to orphan members of the superfamily RZR/ROR. Read More

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Conformational Dynamics Allows Sampling of an "Active-like" State by Oncogenic K-Ras-GDP.

J Mol Biol 2022 Jun 22:167695. Epub 2022 Jun 22.

Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, U.S.A. Electronic address:

Mutations in K-Ras GTPase replacing Gly12 with either Asp or Val are common in cancer. These mutations decelerate intrinsic and catalyzed GTP hydrolysis, leading to accumulation of K-Ras-GTP in cells. Signaling cascades initiated by K-Ras-GTP promote cell proliferation, survival, and invasion. Read More

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Methionine oxidation activates pyruvate kinase M2 to promote pancreatic cancer metastasis.

Mol Cell 2022 Jun 18. Epub 2022 Jun 18.

Institute for Cancer Genetics, Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address:

Cancer mortality is primarily a consequence of its metastatic spread. Here, we report that methionine sulfoxide reductase A (MSRA), which can reduce oxidized methionine residues, acts as a suppressor of pancreatic ductal adenocarcinoma (PDA) metastasis. MSRA expression is decreased in the metastatic tumors of PDA patients, whereas MSRA loss in primary PDA cells promotes migration and invasion. Read More

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Machine-learning-optimized Cas12a barcoding enables the recovery of single-cell lineages and transcriptional profiles.

Mol Cell 2022 Jun 22. Epub 2022 Jun 22.

Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Wu Tsai Neuroscience Institute, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address:

The development of CRISPR-based barcoding methods creates an exciting opportunity to understand cellular phylogenies. We present a compact, tunable, high-capacity Cas12a barcoding system called dual acting inverted site array (DAISY). We combined high-throughput screening and machine learning to predict and optimize the 60-bp DAISY barcode sequences. Read More

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Mitochondrial protein import stress regulates the LC3 lipidation step of mitophagy through NLRX1 and RRBP1.

Mol Cell 2022 Jun 16. Epub 2022 Jun 16.

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address:

Protein import into mitochondria is a highly regulated process, yet how cells clear mitochondria undergoing dysfunctional protein import remains poorly characterized. Here we showed that mitochondrial protein import stress (MPIS) triggers localized LC3 lipidation. This arm of the mitophagy pathway occurs through the Nod-like receptor (NLR) protein NLRX1 while, surprisingly, without the engagement of the canonical mitophagy protein PINK1. Read More

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Efficient delivery of PKN3 shRNA for the treatment of breast cancer via lipid nanoparticles.

Bioorg Med Chem 2022 Jun 13;69:116884. Epub 2022 Jun 13.

School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China. Electronic address:

Protein kinase N3 (PKN3), an AGC-family member, is often overexpressed in breast tumor cells. RNAi therapy is a promising approach to inhibit tumor growth by reducing the expression of PKN3. In this report, lipid nanoparticles encapsulated with new shRNA PKN3 (SS-LNP/shPKN3) with redox-responsiveness were developed in order to specifically down-regulate the expression of PKN3 for breast cancer treatment. Read More

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pH-responsive Mannose-modified ferrocene Metal-Organic frameworks with rare earth for Tumor-targeted synchronous Chemo/Chemodynamic therapy.

Bioorg Med Chem 2022 Jun 14;69:116885. Epub 2022 Jun 14.

Shaanxi Key Laboratory of Natural Products and Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, China. Electronic address:

The combination of chemodynamic therapy (CDT) and chemotherapy is a promising strategy to achieve enhanced anticancer effects. Metal-organic frameworks (MOFs), as multifunctional drug delivery vehicles, have received extensive attention in the biomedical field. Carbohydrate has excellent biocompatibility and targeting ability, which can be used as a targeting ligand due to a specific recognition with glycoprotein receptors that overexpress on cancer cell membranes. Read More

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Characteristics of tumor infiltrating lymphocytes in sinonasal mucosal melanoma and prognosis for patients.

Curr Probl Cancer 2022 Jun 11;46(4):100878. Epub 2022 Jun 11.

Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China. Electronic address:

The significance of tumor infiltrating lymphocytes (TILs) in melanoma has been studied for a long time, but, to date, there has been insufficient research on TILs in sinonasal mucosal melanoma. The purpose of this study was to analyze the correlation between TILs and prognosis for Chinese patients with sinonasal mucosal melanoma, and to clarify the significance of TILs in prognosis. As a retrospective cohort study, 44 cases of malignant melanoma in head and neck mucosa were studied by immunohistochemical staining. Read More

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Steroid glycosides isolated from Paris polyphylla var. chinensis aerial parts and paris saponin II induces G1/S-phase MCF-7 cell cycle arrest.

Carbohydr Res 2022 Jun 15;519:108613. Epub 2022 Jun 15.

College of Pharmacy, Korea University, Sejong, 30019, Republic of Korea. Electronic address:

In our previous research on Vietnamese medicinal plants, we found that the ethanolic extract of the aerial parts of Paris polyphylla var. chinensis exhibited cytotoxic effects in vitro in the MCF-7 human cancer cell line. Here, we used combined chromatographic separations to isolate six compounds including a new steroid glycoside, paripoloside A (3), and five known compounds, from the butanol extract of the aerial parts of P. Read More

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Celastrol upregulated ATG7 triggers autophagy via targeting Nur77 in colorectal cancer.

Phytomedicine 2022 Jun 16;104:154280. Epub 2022 Jun 16.

Department of Pharmacy, Huashan Hospital, Fudan University, No.12 Urumqi Middle Road, Shanghai 200040, China. Electronic address:

Background: Celastrol is a biologically active ingredient extracted from Tripterygium wilfordii that has exerted properties of anti-cancer. We explored the anti-tumor activities of celastrol against colorectal cancer (CRC) and the potential signaling pathways involved in its mechanism in this study.

Purpose: The main purpose was to investigate the anti-CRC effects of celastrol and its novel potential mechanisms. Read More

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Pectolinarigenin acts as a potential anti-osteosarcoma agent via mediating SHP-1/JAK2/STAT3 signaling.

Biomed Pharmacother 2022 Jun 22;153:113323. Epub 2022 Jun 22.

Department of Orthopedics, Shanghai Bone Tumor Institution, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, PR China. Electronic address:

Signal transducer and activator of transcription 3 (STAT3) plays essential roles in cancer progression and has been considered as a promising target for cancer therapy. Here, we used a dual luciferase assay to identify that pectolinarigenin inhibited STAT3 transcriptional activity. Further, results showed pectolinarigenin inhibited constitutive and IL6 induced STAT3 signaling, diminished the accumulation of STAT3 in the nucleus, dimerization and blocked STAT3 DNA binding activity. Read More

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Cancer multidrug-resistance reversal by ABCB1 inhibition: A recent update.

Eur J Med Chem 2022 Jun 17;239:114542. Epub 2022 Jun 17.

Department of Natural Products, Chemical Sciences, National Institute of Pharmaceutical Education and Research-Hyderabad, Hyderabad, Balanagar, 500037, India. Electronic address:

Chemotherapy is one of the most common treatments for cancer that uses one or more anti-cancer drugs as a part of the standardized chemotherapy regimen. Cytotoxic chemicals delay and prevent cancer cells from multiplying, invading, and metastasizing. However, the significant drawbacks of cancer chemotherapy are the lack of selectivity of the cytotoxic drugs to tumour cells and normal cells and the development of resistance by cells for the particular drug or the combination of drugs. Read More

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