☆ 4.7 Review

An overview of the past decade of bufalin in the treatment of refractory and drug-resistant cancers: current status, challenges, and future perspectives

FRONTIERS IN PHARMACOLOGY (2023)

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Article Chemistry, Applied

Two new polyamine alkaloids from the Bufo viridis toad venom

Qiang Dong et al.

Summary: Two new polyamine alkaloids were isolated from Bufo viridis toad venom, along with four known alkaloids. The structures of these compounds were identified and their cytotoxicity against human cancer cell lines was tested, showing no toxicity.

NATURAL PRODUCT RESEARCH (2023)

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Review Oncology

Advances in the structure, mechanism and targeting of chemoresistance-linked ABC transporters

Andaleeb Sajid et al.

Summary: Cancer cells often develop resistance to anticancer drugs, primarily through the overexpression of ABC transporters. Recent studies on ABCB1, ABCG2, and ABCC1 have provided insights into their structure and function, leading to the development of new therapeutic approaches. It is recommended to use these findings in clinical trials to enhance the efficacy of chemotherapy for cancer patients.

NATURE REVIEWS CANCER (2023)

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Article Plant Sciences

Screening of Bufadienolides from Toad Venom Identifies Gammabufotalin as a Potential Anti-inflammatory Agent

Yuanru Zheng et al.

Summary: The anti-inflammatory effects of 14 bufadienolides from toad venom were evaluated using zebrafish as a drug screening model. Most of the bufadienolides showed significant anti-inflammatory effects in different zebrafish inflammatory models. Gammabufotalin was found to inhibit inflammation by suppressing specific signal pathways. This study confirms the potential of zebrafish in drug screening and provides insights into the anti-inflammatory effects of bufadienolides from toad venom.

PLANTA MEDICA (2022)

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Article Integrative & Complementary Medicine

Bufalin Induces Programmed Necroptosis in Triple-Negative Breast Cancer Drug-Resistant Cell Lines through RIP1/ROS-Mediated Pathway

Liu Xiao-dan et al.

Summary: Bufalin could induce necroptosis through RIP1/ROS-mediated pathway to kill the drug-resistant TNBC cell lines, providing experimental evidence for potential clinical application.

CHINESE JOURNAL OF INTEGRATIVE MEDICINE (2022)

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Article Pharmacology & Pharmacy

Nuclear TIGAR mediates an epigenetic and metabolic autoregulatory loop via NRF2 in cancer therapeutic resistance

Hong Wang et al.

Summary: Metabolic and epigenetic reprogramming contribute to cancer therapeutic resistance. In this study, it was found that TIGAR, an antioxidant and glucose metabolic regulator, interacts with NRF2 to stimulate NSD2 expression. Nuclear accumulation of TIGAR is associated with therapeutic resistance and poor survival.

ACTA PHARMACEUTICA SINICA B (2022)

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Article Mathematical & Computational Biology

Alisol B 23-Acetate Increases the Antitumor Effect of Bufalin on Liver Cancer through Inactivating Wnt/β-Catenin Axis

Miaoqing Ye et al.

Summary: This study found that alisol B 23-acetate could enhance the anticancer activity of bufalin in liver cancer. The activation of the Wnt/beta-catenin axis might be a new method for treating liver cancer.

COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Synthesis and Biological Evaluation of Novel Bufalin Derivatives

VishnuPriya Sampath et al.

Summary: Two novel bufalin derivatives were synthesized and their pharmacological properties were characterized in this study. The compounds exhibited similar biological activities to other CS but with reduced cytotoxicity, suggesting their potential as drugs for the treatment of heart failure and arrhythmias.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Review Cell Biology

Cell cycle on the crossroad of tumorigenesis and cancer therapy

Jing Liu et al.

Summary: Cell cycle aberrancy is a fundamental mechanism underlying tumorigenesis, and therapies targeting cell cycle machinery components can not only suppress cancer cell division but also reverse cancer metabolism and restore cancer immune surveillance. Recently, proteolysis targeting chimeras (PROTACs) have been used to target oncogenic proteins related to cell cycle progression for more effective tumor suppression.

TRENDS IN CELL BIOLOGY (2022)

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Article Pharmacology & Pharmacy

Overexpression of ABCB1 Associated With the Resistance to the KRAS-G12C Specific Inhibitor ARS-1620 in Cancer Cells

Xing-Duo Dong et al.

Summary: This study investigated the potential drug resistance mechanism of the KRAS-G12C inhibitor ARS-1620 associated with ABCB1. The findings indicated that ARS-1620 could be competitively pumped out by ABCB1 in cancer cells and significantly stimulated the ATPase activity of ABCB1. These findings suggest that the potential influence of ARS-1620-related cancer therapy on ABCB1-overexpressing cancer cells should be considered in future clinical applications.

FRONTIERS IN PHARMACOLOGY (2022)

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Article Chemistry, Medicinal

Therapeutic Activity of the Lansoprazole Metabolite 5-Hydroxy Lansoprazole Sulfide in Triple-Negative Breast Cancer by Inhibiting the Enoyl Reductase of Fatty Acid Synthase

Jenny Beebe et al.

Summary: Fatty acid synthase (FASN) is overexpressed in cancer and not in normal tissues, and proton pump inhibitors (PPIs), approved for digestive disorders, have been found to inhibit FASN with anticancer activities. Metabolites of PPIs may contribute to the lasting anticancer effects by inhibiting FASN.

JOURNAL OF MEDICINAL CHEMISTRY (2022)

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Review Pharmacology & Pharmacy

Therapeutic implication of carbon monoxide in drug resistant cancers

Qingbin Cui et al.

Summary: Drug resistance is a major obstacle in cancer treatment, but the use of carbon monoxide (CO) as a gas signaling molecule has gained attention for overcoming this problem. CO can inhibit ATP production pathways and angiogenesis in cancer cells, leading to synergistic effects when combined with certain drugs. This review summarizes the research on using CO to treat drug-resistant cancers in the past decade and provides detailed explanations of the underlying mechanisms.

BIOCHEMICAL PHARMACOLOGY (2022)

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Article Biochemistry & Molecular Biology

A novel survivin dimerization inhibitor without a labile hydrazone linker induces spontaneous apoptosis and synergizes with docetaxel in prostate cancer cells

Robert Peery et al.

Summary: Survivin, an important protein upregulated in various cancers, is challenging to target for therapy. Inhibition of survivin dimerization has been found to promote its degradation and show potential for cancer treatment. LQZ-7F, a small-molecule inhibitor, exhibits strong biological activity and synergism in combination with docetaxel.

BIOORGANIC & MEDICINAL CHEMISTRY (2022)

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Article Pharmacology & Pharmacy

Bufalin exacerbates Photodynamic therapy of colorectal cancer by targeting SRC-3/HIF-1? pathway

Zeting Yuan et al.

Summary: This study designed iRGD-modified nanoparticles to co-deliver mTHPC and BU, aiming to enhance the efficacy of photodynamic therapy (PDT) in colorectal cancer (CRC). The nanoparticles passively accumulated in tumor cells, with mTHPC inducing apoptosis and death under laser irradiation, while the sustained release of BU inhibited hypoxia and angiogenesis by targeting the SRC-3/HIF-1α pathway.

INTERNATIONAL JOURNAL OF PHARMACEUTICS (2022)

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Article Oncology

Breast Cancer Statistics, 2022

Angela N. Giaquinto et al.

Summary: This article provides an update on female breast cancer statistics in the United States, including data on incidence, mortality, survival, and mammography screening. It shows that breast cancer incidence rates have increased over the past few decades, driven by localized-stage and hormone receptor-positive disease. However, breast cancer mortality rates have been steadily declining since 1989, although at a slower pace in recent years. Despite lower incidence rates, there remains a racial disparity in breast cancer mortality, with higher rates among Black women compared to White women.

CA-A CANCER JOURNAL FOR CLINICIANS (2022)

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Article Oncology

Osteosarcoma and causes of death: A report of 1520 deceased patients from the Cooperative Osteosarcoma Study Group (COSS)

Stefan S. Bielack et al.

Summary: The main cause of death for osteosarcoma patients is the malignancy itself, mostly due to multiple relapses. However, about 10% of fatalities are caused by other documented reasons. Comprehensive analyses like this can provide valuable knowledge and potentially prevent some of these deaths.

EUROPEAN JOURNAL OF CANCER (2022)

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Review Oncology

Recent advances in therapeutic strategies for triple-negative breast cancer

Yun Li et al.

Summary: Triple-negative breast cancer (TNBC) is a highly malignant subtype of breast cancer with a poor prognosis. Current treatment options are limited, but targeted therapies focusing on DNA repair pathways, androgen receptor signaling pathways, kinases, and immunotherapy have shown promise.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2022)

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Article Gastroenterology & Hepatology

Global burden of primary liver cancer in 2020 and predictions to 2040

Harriet Rumgay et al.

Summary: The burden of liver cancer varies across the world, and it is a major cause of death in many countries. The number of liver cancer cases and deaths is predicted to increase, with a significant rise expected by 2040.

JOURNAL OF HEPATOLOGY (2022)

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Article Oncology

Identification of Src Family Kinases as Potential Therapeutic Targets for Chemotherapy-Resistant Triple Negative Breast Cancer

Ishwar N. Kohale et al.

Summary: Breast cancer is the leading cause of cancer-related deaths in women globally, with triple negative breast cancer (TNBC) known for being highly aggressive and resistant to chemotherapy. In this study, the researchers identified Src family kinases (SFKs) as potential drug targets for chemotherapy-resistant TNBC. However, the prevalence of SFK-driven tumors was found to be low in human tumor tissue specimens. These findings highlight the importance of characterizing phosphotyrosine signaling profiles for patient stratification and therapeutic options.

CANCERS (2022)

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Review Oncology

Current Landscape of Therapeutic Resistance in Lung Cancer and Promising Strategies to Overcome Resistance

Adnin Ashrafi et al.

Summary: Despite initial response to therapy, many lung cancer patients develop resistance, impacting treatment success. Research into resistance mechanisms and novel approaches may delay resistance and improve outcomes. Understanding diverse resistance mechanisms is crucial for overcoming therapeutic resistance and improving clinical outcomes.

CANCERS (2022)

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Review Medicine, General & Internal

Mechanisms on chemotherapy resistance of colorectal cancer stem cells and research progress of reverse transformation: A mini-review

Lei Chen et al.

Summary: This study reviews the mechanisms of chemotherapy resistance in colorectal cancer (CRC), primarily focusing on cancer stem cells (CSCs). The research also discusses potential strategies to overcome chemotherapy resistance and eliminate CSCs, providing promising insights for CRC treatment.

FRONTIERS IN MEDICINE (2022)

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Review Biochemistry & Molecular Biology

Roles of RIPK3 in necroptosis, cell signaling, and disease

Michael J. Morgan et al.

Summary: This article discusses the roles of RIPK3 in cell signaling and necroptosis, as well as the pathways that trigger RIPK3 activation and cell death. The significance of this research lies in revealing the association of necroptosis with inflammation and the immune system, and exploring the potential role of RIPK3 in diseases.

EXPERIMENTAL AND MOLECULAR MEDICINE (2022)

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Article Medicine, Research & Experimental

Combination Treatment of Sorafenib and Bufalin Induces Apoptosis in NCI-H292 Human Lung Cancer Cells In Vitro

Jung-Yu Kuo et al.

Summary: This study investigated the effects and molecular mechanisms of sorafenib and bufalin combination therapy on lung cancer cells. The results showed that the combined treatment exhibited more potent cytotoxic effects and cell apoptosis compared to sorafenib or bufalin treatment alone. The combination treatment activated ROS-, mitochondria-, and caspase-signaling pathways, leading to enhanced apoptotic cell death.

IN VIVO (2022)

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Article Biochemistry & Molecular Biology

Novel Strategies for Solubility and Bioavailability Enhancement of Bufadienolides

Huili Shao et al.

Summary: Toad venom contains bufadienolides, which have various pharmacological activities including antitumor, cardiovascular, anti-inflammatory, analgesic, and immunomodulatory effects. However, the clinical application of bufadienolides is limited due to their poor solubility and bioavailability. Strategies such as structural modification and drug delivery systems have been explored to overcome these limitations.

MOLECULES (2022)

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Review Biochemistry & Molecular Biology

The next tier of EGFR resistance mutations in lung cancer

Hannah L. Tumbrink et al.

Summary: EGFR mutations play a major role in druggable targets for lung adenocarcinoma, and optimization of EGFR inhibitors has significantly impacted treatment options. However, the emergence of resistance mutations during drug treatment has driven the need for rapid understanding of individual mutations for developing next-generation inhibitors. The field currently faces a large number of combinations of activating mutations and distinct resistance mutations, alongside the approval of osimertinib as a frontline drug for EGFR-mutant lung cancer.

ONCOGENE (2021)

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Review Medicine, General & Internal

ATP-binding cassette (ABC) transporters in cancer: A review of recent updates

Jing-Quan Wang et al.

Summary: The ATP-binding cassette (ABC) transporter superfamily is a large membrane protein family found in various organisms, playing a critical role in multidrug resistance and cancer, as well as other biological functions. Research on the structure, function, and transport profile of ABC transporters may provide insights for developing more effective therapies for cancer drug resistance.

JOURNAL OF EVIDENCE BASED MEDICINE (2021)

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Article Oncology

Recent incidence trend of elderly patients with glioblastoma in the United States, 2000-2017

Boran Chen et al.

Summary: The overall incidence of glioblastoma in the elderly population remained stable between 2000 and 2017. There was a non-significant increasing tendency for all elderly patients, while specific subgroups showed significantly increasing or decreasing trends in incidence rates. Age had an impact on the incidence trends, but period and cohort effects were not evident. Future research on specific molecular subgroups is needed to further understand the etiology of glioblastoma.

BMC CANCER (2021)

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Review Pharmacology & Pharmacy

Multidrug resistance proteins (MRPs): Structure, function and the overcoming of cancer multidrug resistance

Jing-Quan Wang et al.

Summary: ABC transporters mediate the translocation of structurally and mechanistically distinct substrates against steep concentration gradients using ATP energy. The ABCC subfamily is the largest in humans, with 13 members, including 9 multidrug resistance proteins that can extrude chemotherapeutic agents from tumor cells. Additionally, MRPs are also involved in the efflux of physiologically important organic anions and are potential targets for overcoming cancer multidrug resistance.

DRUG RESISTANCE UPDATES (2021)

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Article Immunology

Bufalin enhances the killing efficacy of NK cells against hepatocellular carcinoma by inhibiting MICA shedding

Rao Fu et al.

Summary: Bufalin can balance NK cell receptors, inhibit MICA shedding, activate NK cells, and enhance immune surveillance.

INTERNATIONAL IMMUNOPHARMACOLOGY (2021)

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Article Chemistry, Multidisciplinary

Co-delivery of bufalin and nintedanib via albumin sub-microspheres for synergistic cancer therapy

Ying Xu et al.

Summary: Albumin sub-microspheres developed using coaxial-electrospray technology for co-delivery of bufalin and nintedanib show superior tumor targeting efficiency and synergistic therapeutic effect. This provides a novel method for fabricating an albumin-based drug delivery system and a potential efficient combination therapeutic strategy for tumor treatment.

JOURNAL OF CONTROLLED RELEASE (2021)

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Review Chemistry, Medicinal

Cancer Stem Cells and Nucleolin as Drivers of Carcinogenesis

Laura Sofia Carvalho et al.

Summary: This review discusses the clonal evolution of cancer stem cells and the plasticity of cancer cells, as well as the role of nucleolin in cancer hallmarks. These factors play important roles in tumor heterogeneity, therapy resistance, and relapse.

PHARMACEUTICALS (2021)

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Article Oncology

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hyuna Sung et al.

Summary: The global cancer burden in 2020 saw an estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths. Female breast cancer surpassed lung cancer as the most commonly diagnosed cancer, while lung cancer remained the leading cause of cancer death. These trends are expected to rise in 2040, with transitioning countries experiencing a larger increase compared to transitioned countries due to demographic changes and risk factors associated with globalization and a growing economy. Efforts to improve cancer prevention measures and provision of cancer care in transitioning countries will be crucial for global cancer control.

CA-A CANCER JOURNAL FOR CLINICIANS (2021)

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Article Biochemistry & Molecular Biology

The Novel benzamide Derivative, VKNG-2, Restores the Efficacy of Chemotherapeutic Drugs in Colon Cancer Cell Lines by Inhibiting the ABCG2 Transporter

Silpa Narayanan et al.

Summary: The study showed that the novel benzamide derivative VKNG-2 can reverse MDR caused by overexpression of ABCG2 transporter in colon cancer cells; VKNG-2 significantly improves the efficacy of anticancer drugs in vitro and works by inhibiting the efflux function of the ABCG2 transporter.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Oncology

Effect of PI3K/AKT/mTOR Signaling Pathway on Regulating and Con- trolling the Anti-Invasion and Metastasis of Hepatoma Cells by Bufalin

Xia Sheng et al.

Summary: This study explored the effect of Bufalin on regulating invasion and metastasis of liver cancer cells through the PI3K/AKT/mTOR autophagy-related signaling pathway. Inhibiting autophagy enhanced the inhibitory effect of Bufalin on cell adhesion, migration, and invasion. Bufalin significantly influenced the expression of key proteins involved in proliferation, matrix degradation, and angiogenesis, suggesting its potential as a novel therapeutic strategy for preventing metastasis of liver cancer.

RECENT PATENTS ON ANTI-CANCER DRUG DISCOVERY (2021)

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Review Oncology

Targeting Cancer Stem Cells with Repurposed Drugs to Improve Current Therapies

Dunne Fong et al.

Summary: Cancer is a complex multistep process involving genetic and environmental factors leading to genetic and epigenetic changes. Cancer stem cells play a crucial role in tumor progression and are a subpopulation of tumor cells with self-renewal and differentiation abilities. Repurposing FDA-approved drugs to target resistant cancer cells, such as CSCs, can improve cancer treatment efficacy.

RECENT PATENTS ON ANTI-CANCER DRUG DISCOVERY (2021)

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Review Pharmacology & Pharmacy

DNA Repair Pathways in Cancer Therapy and Resistance

Lan-ya Li et al.

Summary: DNA repair pathways play a crucial role in maintaining genetic stability in mammalian cells exposed to DNA-damaging agents, and their deregulation is associated with cancer development. Targeting DNA repair pathways could be a potential therapeutic approach for enhancing the effectiveness of cancer treatments.

FRONTIERS IN PHARMACOLOGY (2021)

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Review Chemistry, Medicinal

Toad venom: A comprehensive review of chemical constituents, anticancer activities, and mechanisms

Fang-Jie Li et al.

Summary: Toad venom, a traditional natural medicine in China, has shown potential in cancer treatment with its wide range of anticancer activities, likely through mechanisms such as apoptosis induction, cell cycle arrest, metastasis suppression, reversal of drug resistance, or growth inhibition of cancer cells. Research on the chemical constituents and anticancer mechanisms of toad venom is important for further studies and development of cancer treatments.

ARCHIV DER PHARMAZIE (2021)

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Article Oncology

Bufalin targets the SRC-3/MIF pathway in chemoresistant cells to regulate M2 macrophage polarization in colorectal cancer

Jinbao Chen et al.

Summary: Bufalin can reduce the polarization of M2 macrophages induced by chemoresistant cells, but has no direct effect on M2 macrophage polarization itself. Bufalin targets the SRC-3 protein to reduce MIF release and regulate the polarization of M2 macrophages. Additionally, Cinobufacini, which contains Bufalin as its main active monomer, can enhance the anti-tumour effect of oxaliplatin by regulating M2 macrophage polarization in vivo and in the clinic.

CANCER LETTERS (2021)

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Article Pharmacology & Pharmacy

Downregulation of ATP1A1 Expression by Panax notoginseng (Burk.) FH Chen Saponins: A Potential Mechanism of Antitumor Effects in HepG2 Cells and In Vivo

Xiao-Yi Feng et al.

Summary: The study demonstrates that Panax notoginseng saponins can inhibit the proliferation of hepatocellular carcinoma cells by downregulating ATP1A1 and modulating signal transduction pathways.

FRONTIERS IN PHARMACOLOGY (2021)

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Article Pharmacology & Pharmacy

MET inhibitor tepotinib antagonizes multidrug resistance mediated by ABCG2 transporter: In vitro and in vivo study

Zhuo-Xun Wu et al.

Acta Pharmaceutica Sinica B (2021)

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Review Biochemistry & Molecular Biology

HGF/c-MET pathway in cancer: from molecular characterization to clinical evidence

Jianjiang Fu et al.

Summary: This review comprehensively explores the role of the HGF/c-MET signaling pathway in cancers, highlighting its influence on cellular processes, genomic characterization in carcinogenesis, and malignant biological behaviors. Although monotherapy targeting HGF/c-MET has shown limited clinical efficacy in most cancers, the major challenge in the future lies in exploring more options of combinational targeted therapy in cancers.

ONCOGENE (2021)

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Article Medicine, Research & Experimental

Effects of low-dose bufalin combined with hydroxycamptothecin on human castration-resistant prostate cancer xenografts in nude mice

Renze Gu et al.

Summary: Prostate cancer is the most prevalent tumor in men globally. This study demonstrated that the combination of low-dose bufalin and hydroxycamptothecin significantly inhibited CRPC tumors in vivo by regulating the PI3K/AKT/GSK-3 beta and p53-dependent apoptosis signaling pathways.

EXPERIMENTAL AND THERAPEUTIC MEDICINE (2021)

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Article Chemistry, Multidisciplinary

Detecting Attomolar DNA-Damaging Anticancer Drug Activity in Cell Lysates with Electrochemical DNA Devices

Ashan P. Wettasinghe et al.

Summary: In this study, electrochemical DNA devices were used to quantify and understand the cancer-specific DNA-damaging activity of an emerging drug at extremely low concentrations. The results demonstrated the high potency and selectivity of the drug for NQO1+ cancer cells, and highlighted the potential of these devices in identifying promising drugs requiring improved cell permeability.

ACS SENSORS (2021)

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Article Oncology

Deep immune profiling reveals targetable mechanisms of immune evasion in immune checkpoint inhibitor-refractory glioblastoma

Erin F. Simonds et al.

Summary: This study compared the tumor immune microenvironments of ICI-responsive and ICI-refractory tumors, identifying T cells and dendritic cells as key factors associated with ICI sensitivity. Mouse models suggested that poor antigen presentation in the brain may contribute to ICI resistance in GBM. Rational immunotherapeutic combinations targeting DCs and PD-L1+ tumor-associated macrophages showed promising results in vivo.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2021)

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Apoptosis Deregulation and the Development of Cancer Multi-Drug Resistance

Christiana M. Neophytou et al.

Summary: This review discusses the deregulation of apoptotic pathways as a key factor leading to multidrug resistance (MDR) in cancer cells, along with the impact of the tumor microenvironment on apoptosis in MDR tumors. Therapeutic approaches targeting Bcl-2 family members, IAPs, and AKT, as well as the potential of epigenetic modifications in reversing MDR, are highlighted as important strategies against drug resistance.

CANCERS (2021)

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Targeting cancer stem cells in refractory cancer

Norikatsu Miyoshi et al.

Summary: Refractory cancer is often caused by a specific population of tumor cells with stemness characteristics called cancer stem cells (CSCs), which have the ability for self-renewal and multipotent differentiation. These cells can be identified based on cell surface markers and biological functions, and new techniques for identifying and quantifying them in situ are valuable for evaluating therapy effects. Targeting and quantifying CSCs with therapeutic and diagnostic methodologies could be crucial for eradicating refractory cancer.

REGENERATIVE THERAPY (2021)

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Article Oncology

Liver Cancer Survival: A Real World Observation of 45 Years with 32,556 Cases

Jian-Guo Chen et al.

Summary: The long-term trend of liver cancer survival in Qidong, China based on real-world data from 1972 to 2016 shows significant improvement. There are gender and age differences in the survival rate of liver cancer, with the best 5-year survival rates observed in the age group of 55-64.

JOURNAL OF HEPATOCELLULAR CARCINOMA (2021)

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Article Medicine, Research & Experimental

Insights on the structure-function relationship of human multidrug resistance protein 7 (MRP7/ABCC10) from molecular dynamics simulations and docking studies

Jing-Quan Wang et al.

Summary: This study constructed and validated a homology model for human MRP7 based on cryo-EM structures, obtained structure-function relationship of MRP7 from molecular dynamics simulations and docking studies, discussed motion patterns correlated with efflux mechanism, and described predicted substrate- and modulator-binding sites of MRP7 for the first time.

MEDCOMM (2021)

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Article Oncology

Colorectal cancer statistics, 2020

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CA-A CANCER JOURNAL FOR CLINICIANS (2020)

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Review Pharmacology & Pharmacy

Targeting the ubiquitin-proteasome pathway to overcome anti-cancer drug resistance

Silpa Narayanan et al.

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Article Oncology

Reversal Effect of ALK Inhibitor NVP-TAE684 on ABCG2-Overexpressing Cancer Cells

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FRONTIERS IN ONCOLOGY (2020)

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Article Oncology

MK-2206 and Standard Neoadjuvant Chemotherapy Improves Response in Patients With Human Epidermal Growth Factor Receptor 2-Positive and/or Hormone Receptor-Negative Breast Cancers in the I-SPY 2 Trial

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JOURNAL OF CLINICAL ONCOLOGY (2020)

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Article Pharmacology & Pharmacy

19-Hydroxy-bufalin, a major bufadienolide isolated from the parotoid gland secretions of the Panamanian endemic toad Rhinella centralis (Bufonidae), inhibits the growth of Trypanosoma cruzi

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TOXICON (2020)

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Article Biotechnology & Applied Microbiology

Bufalin Induces Glioma Cell Death by Apoptosis or Necroptosis

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OncoTargets and Therapy (2020)

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Prognosis of stage III cervical cancer: a two-way outcome study

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Targeting the HGF/MET Axis in Cancer Therapy: Challenges in Resistance and Opportunities for Improvement

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Structural and Mechanistic Principles of ABC Transporters

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ANNUAL REVIEW OF BIOCHEMISTRY, VOL 89 (2020)

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Two New Indole Alkaloids from Toad Venom of Bufo bufo gargarizans

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Bufalin attenuates triple-negative breast cancer cell stemness by inhibiting the expression of SOX2/OCT4

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The sodium pump α1 subunit regulates bufalin sensitivity of human glioblastoma cells through the p53 signaling pathway

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Global, regional, and national burden of brain and other CNS cancer, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016

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Bufalin induces protective autophagy by Cbl-b regulating mTOR and ERK signaling pathways in gastric cancer cells

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CELL BIOLOGY INTERNATIONAL (2019)

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Jean M. Mulcahy Levy et al.

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INTERNATIONAL JOURNAL OF CANCER (2019)

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Phase II trial of AKT inhibitor MK-2206 in patients with advanced breast cancer who have tumors with PIK3CA or AKT mutations, and/or PTEN loss/PTEN mutation

Yan Xing et al.

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Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors

Prashanth Rawla et al.

WORLD JOURNAL OF ONCOLOGY (2019)

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Review Oncology

Epidemiology of Prostate Cancer

Prashanth Rawla

WORLD JOURNAL OF ONCOLOGY (2019)

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Review Oncology

Cancer stem cells in neuroblastoma therapy resistance

Natarajan Aravindan et al.

CANCER DRUG RESISTANCE (2019)

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Article Hematology

Bufalin Enhances the Cytotoxity of Human Multiple Myeloma Cells H929 to AKT Inhibitor MK2206: The Role of Protein AKT Phosphorylation

He Huang et al.

INDIAN JOURNAL OF HEMATOLOGY AND BLOOD TRANSFUSION (2018)

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Article Plant Sciences

A new indole alkaloid from the traditional Chinese medicine Chansu

Ying-Hui Dai et al.

JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH (2018)

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Review Oncology

Is the blood-brain barrier really disrupted in all glioblastomas? A critical assessment of existing clinical data

Jann N. Sarkaria et al.

NEURO-ONCOLOGY (2018)

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Article Hematology

Bufalin Enhances the Cytotoxity of Human Multiple Myeloma Cells H929 to AKT Inhibitor MK2206: The Role of Protein AKT Phosphorylation

He Huang et al.

INDIAN JOURNAL OF HEMATOLOGY AND BLOOD TRANSFUSION (2018)

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Article Medicine, Research & Experimental

Bufalin inhibits glioblastoma growth by promoting proteasomal degradation of the Na+/K+-ATPase α1 subunit

Yu-Long Lan et al.

BIOMEDICINE & PHARMACOTHERAPY (2018)

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Article Oncology

Bufalin inhibits human breast cancer tumorigenesis by inducing cell death through the ROS-mediated RIP1/RIP3/PARP-1 pathways

Yanlan Li et al.

CARCINOGENESIS (2018)

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Article Oncology

Synergistic anti-hepatoma effect of bufalin combined with sorafenib via mediating the tumor vascular microenvironment by targeting mTOR/VEGF signaling

Haiyong Wang et al.

INTERNATIONAL JOURNAL OF ONCOLOGY (2018)

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Article Oncology

Synergistic anticancer effects of bufalin and sorafenib by regulating apoptosis associated proteins

Haiyong Wang et al.

MOLECULAR MEDICINE REPORTS (2018)

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Article Oncology

Bufalin and 5-fluorouracil synergistically induce apoptosis in colorectal cancer cells

Xiao-Yu Dai et al.

ONCOLOGY LETTERS (2018)

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Article Medicine, Research & Experimental

Bufalin Enhances Immune Responses in Leukemic Mice Through Enhancing Phagocytosis of Macrophage In Vivo

Yung-Luen Shih et al.

IN VIVO (2018)

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Review Pharmacology & Pharmacy

Modulating ROS to overcome multidrug resistance in cancer

Qingbin Cui et al.

DRUG RESISTANCE UPDATES (2018)

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Review Oncology

Revisiting the role of ABC transporters in multidrug-resistant cancer

Robert W. Robey et al.

NATURE REVIEWS CANCER (2018)

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Review Orthopedics

Osteosarcoma: a comprehensive review

Amirhossein Misaghi et al.

SICOT-J (2018)

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Review Cell Biology

Autophagy pathway: Cellular and molecular mechanisms

Li Yu et al.

AUTOPHAGY (2018)

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Article Biochemistry & Molecular Biology

Novel augmentation by bufalin of protein kinase C-induced cyclooxygenase-2 and IL-8 production in human breast cancer cells

Hsiao-Ting Chen et al.

INNATE IMMUNITY (2017)

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Article Oncology

Bufalin reverses acquired drug resistance by inhibiting stemness in colorectal cancer cells

Jian Sun et al.

ONCOLOGY REPORTS (2017)

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Article Pharmacology & Pharmacy

Bufalin Inhibits the Inflammatory Effects in Asthmatic Mice through the Suppression of Nuclear Factor-Kappa B Activity

Zibierguli Zhakeer et al.

PHARMACOLOGY (2017)

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Review Oncology

Mechanisms of Therapeutic Resistance in Prostate Cancer

Mary Nakazawa et al.

CURRENT ONCOLOGY REPORTS (2017)

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Article Oncology

Bufalin sensitizes human bladder carcinoma cells to TRAIL-mediated apoptosis

Kyung-Hwa Kang et al.

ONCOLOGY LETTERS (2017)

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Article Cell Biology

Bufalin Inhibits Cellular Proliferation and Cancer Stem Cell-Like Phenotypes via Upregulation of MiR-203 in Glioma

Tao Liu et al.

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY (2017)

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Article Medicine, Research & Experimental

Bufalin enhances radiosensitivity of glioblastoma by suppressing mitochondrial function and DNA damage repair

Xin Zhang et al.

BIOMEDICINE & PHARMACOTHERAPY (2017)

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Review Oncology

Autophagy and multidrug resistance in cancer

Ying-Jie Li et al.

CHINESE JOURNAL OF CANCER (2017)

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Article Chemistry, Multidisciplinary

Bufalin derivative BF211 inhibits proteasome activity in human lung cancer cells in vitro by inhibiting β1 subunit expression and disrupting proteasome assembly

Peng Sun et al.

ACTA PHARMACOLOGICA SINICA (2016)

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Review Pharmacology & Pharmacy

Overcoming ABC transporter-mediated multidrug resistance: Molecular mechanisms and novel therapeutic drug strategies

Wen Li et al.

DRUG RESISTANCE UPDATES (2016)

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Article Plant Sciences

Bufalin inhibits gefitinib resistant NCI-H460 human lung cancer cell migration and invasion in vitro

An-Cheng Huang et al.

JOURNAL OF ETHNOPHARMACOLOGY (2016)

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Article Plant Sciences

Bufalin inhibits pancreatic cancer by inducing cell cycle arrest via the c-Myc/NF-κB pathway

Xia Liu et al.

JOURNAL OF ETHNOPHARMACOLOGY (2016)

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Article Plant Sciences

Chemical profiling and cytotoxicity assay of bufadienolides in toad venom and toad skin

Qiong Meng et al.

JOURNAL OF ETHNOPHARMACOLOGY (2016)

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Article Oncology

Bufalin suppresses cancer stem-like cells in gemcitabine-resistant pancreatic cancer cells via Hedgehog signaling

Haiyong Wang et al.

MOLECULAR MEDICINE REPORTS (2016)

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Article Oncology

Bufalin reverses intrinsic and acquired drug resistance to cisplatin through the AKT signaling pathway in gastric cancer cells

Hongyan Zhao et al.

MOLECULAR MEDICINE REPORTS (2016)

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Article Biochemistry & Molecular Biology

Synthesis and biological evaluation of bufalin-3-yl nitrogen-containing-carbamate derivatives as anticancer agents

Min Lei et al.

STEROIDS (2016)

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Review Gastroenterology & Hepatology

Mechanisms of drug resistance in colon cancer and its therapeutic strategies

Tao Hu et al.

WORLD JOURNAL OF GASTROENTEROLOGY (2016)

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Article Oncology

Bufalin enhances antitumor effect of paclitaxel on cervical tumorigenesis via inhibiting the integrin α2/β5/FAK signaling pathway

Fei Liu et al.

ONCOTARGET (2016)

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Article Oncology

Overexpression of ATPase Na plus /K plus transporting alpha 1 polypeptide, ATP1A1, correlates with clinical diagnosis and progression of esophageal squamous cell carcinoma

I-Chen Wu et al.

ONCOTARGET (2016)

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Article Hematology

Phase II study of an AKT inhibitor MK2206 in patients with relapsed or refractory lymphoma

Yasuhiro Oki et al.

BRITISH JOURNAL OF HAEMATOLOGY (2015)

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Article Cell Biology

Bufalin Inhibits the Differentiation and Proliferation of Cancer Stem Cells Derived from Primary Osteosarcoma Cells through Mir-148a

Yuewen Chang et al.

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY (2015)

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Review Pharmacology & Pharmacy

Overcoming the blood-brain tumor barrier for effective glioblastoma treatment

O. van Tellingen et al.

DRUG RESISTANCE UPDATES (2015)

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Review Pharmacology & Pharmacy

The modulation of ABC transporter-mediated multidrug resistance in cancer: A review of the past decade

Rishil J. Kathawala et al.

DRUG RESISTANCE UPDATES (2015)

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Review Biochemistry & Molecular Biology

Oncogene addiction: pathways of therapeutic response, resistance, and road maps toward a cure

Raymond Pagliarini et al.

EMBO REPORTS (2015)

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Article Integrative & Complementary Medicine

Bufalin Induces Mitochondria-Dependent Apoptosis in Pancreatic and Oral Cancer Cells by Downregulating hTERT Expression via Activation of the JNK/p38 Pathway

Xin Tian et al.

EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE (2015)

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Review Pharmacology & Pharmacy

Mitochondrial ROS and cancer drug resistance: Implications for therapy

Imoh S. Okon et al.

PHARMACOLOGICAL RESEARCH (2015)

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Article Multidisciplinary Sciences

Bufalin Reverses Resistance to Sorafenib by Inhibiting Akt Activation in Hepatocellular Carcinoma: The Role of Endoplasmic Reticulum Stress

Bo Zhai et al.

PLOS ONE (2015)

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Article Multidisciplinary Sciences

Steroid Receptor Coactivator-3 (SRC-3/AIB1) as a Novel Therapeutic Target in Triple Negative Breast Cancer and Its Inhibition with a Phospho-Bufalin Prodrug

Xianzhou Song et al.

PLOS ONE (2015)

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Article Multidisciplinary Sciences

Structures and characterization of digoxin- and bufalin-bound Na+, K+-ATPase compared with the ouabain-bound complex

Mette Laursen et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2015)

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Article Oncology

Bufalin enhances TRAIL-induced apoptosis by redistributing death receptors in lipid rafts in breast cancer cells

Shunchao Yan et al.

ANTI-CANCER DRUGS (2014)

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Article Oncology

Bufalin Is a Potent Small-Molecule Inhibitor of the Steroid Receptor Coactivators SRC-3 and SRC-1

Ying Wang et al.

CANCER RESEARCH (2014)

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Article Cell Biology

Bufalin, a Bioactive Component of the Chinese Medicine Chansu, Inhibits Inflammation and Invasion of Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes

Xiaofeng Rong et al.

INFLAMMATION (2014)

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Article Biochemistry & Molecular Biology

Bufalin Induces the Interplay between Apoptosis and Autophagy in Glioma Cells through Endoplasmic Reticulum Stress

Shuying Shen et al.

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES (2014)

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Article Medicine, Research & Experimental

Bufalin induces growth inhibition, cell cycle arrest and apoptosis in human endometrial and ovarian cancer cells

Noriyuki Takai et al.

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE (2014)

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Article Biochemistry & Molecular Biology

Gamabufotalin, a bufadienolide compound from toad venom, suppresses COX-2 expression through targeting IKKβ/NF-κB signaling pathway in lung cancer cells

Zhenlong Yu et al.

MOLECULAR CANCER (2014)

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Article Chemistry, Applied

Synthesis of bufalin derivatives with inhibitory activity against prostate cancer cells

Xiao-Feng Yuan et al.

NATURAL PRODUCT RESEARCH (2014)

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Article Cell Biology

Anti-Inflammatory and Antinociceptive Activities of Bufalin in Rodents

Lili Wen et al.

MEDIATORS OF INFLAMMATION (2014)

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Article Oncology

Reversal effect of bufalin on multidrug resistance in human hepatocellular carcinoma BEL-7402/5-FU cells

Wei Gu et al.

ONCOLOGY REPORTS (2014)

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Article Oncology

Bufalin exerts antitumor effects by inducing cell cycle arrest and triggering apoptosis in pancreatic cancer cells

Meiying Li et al.

TUMOR BIOLOGY (2014)

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Article Integrative & Complementary Medicine

Bufalin, a component in Chansu, inhibits proliferation and invasion of hepatocellular carcinoma cells

Dong-Ze Qiu et al.

BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE (2013)

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Article Oncology

Arenobufagin, a natural bufadienolide from toad venom, induces apoptosis and autophagy in human hepatocellular carcinoma cells through inhibition of PI3K/Akt/mTOR pathway

Dong-Mei Zhang et al.

CARCINOGENESIS (2013)

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Article Integrative & Complementary Medicine

Bufalin Reverses HGF-Induced Resistance to EGFR-TKIs in EGFR Mutant Lung Cancer Cells via Blockage of Met/PI3k/Akt Pathway and Induction of Apoptosis

Xiao-Hong Kang et al.

EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE (2013)

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Editorial Material Medicine, General & Internal

Mediating Resistance in Oncogene-Driven Cancers

Rafael Rosell

NEW ENGLAND JOURNAL OF MEDICINE (2013)

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Article Biochemistry & Molecular Biology

Synthesis and structure-activity relationships study of cytotoxic bufalin 3-nitrogen-containing-ester derivatives

Biao Ma et al.

STEROIDS (2013)

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Article Biochemistry & Molecular Biology

Bufalin Induces Lung Cancer Cell Apoptosis via the Inhibition of PI3K/Akt Pathway

Zhitu Zhu et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2012)

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Article Oncology

AKT serine/threonine protein kinase modulates bufalin-triggered intrinsic pathway of apoptosis in CAL 27 human oral cancer cells

Shih-Chang Tsai et al.

INTERNATIONAL JOURNAL OF ONCOLOGY (2012)

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Article Oncology

Down-regulation of Cbl-b by bufalin results in up-regulation of DR4/DR5 and sensitization of TRAIL-induced apoptosis in breast cancer cells

Shunchao Yan et al.

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY (2012)

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Article Biochemistry & Molecular Biology

Bufalin enhances the anti-proliferative effect of sorafenib on human hepatocellular carcinoma cells through downregulation of ERK

Yang Gao et al.

MOLECULAR BIOLOGY REPORTS (2012)

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Article Oncology

Bufalin induces apoptosis through activation of both the intrinsic and extrinsic pathways in human bladder cancer cells

Su-Hyun Hong et al.

ONCOLOGY REPORTS (2012)

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Article Oncology

Bufalin enhances the antitumor effect of gemcitabine in pancreatic cancer

Ying Chen et al.

ONCOLOGY LETTERS (2012)

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Article Oncology

Src: a potential target for the treatment of triple-negative breast cancer

D. Tryfonopoulos et al.

ANNALS OF ONCOLOGY (2011)

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Article Biochemistry & Molecular Biology

Bufalin induces autophagy-mediated cell death in human colon cancer cells through reactive oxygen species generation and JNK activation

Chuan-Ming Xie et al.

FREE RADICAL BIOLOGY AND MEDICINE (2011)

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Article Toxicology

Effects of Resibufogenin and Cinobufagin on voltage-gated potassium channels in primary cultures of rat hippocampal neurons

Shuang Hao et al.

TOXICOLOGY IN VITRO (2011)

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Article Oncology

PI3K/Akt is involved in bufalin-induced apoptosis in gastric cancer cells

Dan Li et al.

ANTI-CANCER DRUGS (2009)

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Review Oncology

Tumor resistance to apoptosis

Simone Fulda

INTERNATIONAL JOURNAL OF CANCER (2009)

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