18,504 results match your criteria proteasome inhibitor


Knockdown of CDK5 down-regulates PD-L1 via the ubiquitination-proteasome pathway and improves antitumor immunity in lung adenocarcinoma.

Transl Oncol 2021 Jun 12;14(9):101148. Epub 2021 Jun 12.

Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Road, Shanghai 200030, PR China. Electronic address:

Although immunotherapy (anti-PD-1/PD-L1 antibodies) has been approved for clinical treatment of lung cancer, only a small proportion of patients respond to monotherapy. Hence, understanding the regulatory mechanism of PD-L1 is particularly important to identify optimal combinations. In this study, we found that inhibition of CDK5 induced by shRNA or CDK5 inhibitor leads to reduced expression of PD-L1 protein in human lung adenocarcinoma cells, while the mRNA level is not substantially altered. Read More

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Retrospective study of treatment patterns and outcomes post-lenalidomide for multiple myeloma in Canada.

Eur J Haematol 2021 Jun 15. Epub 2021 Jun 15.

Cross Cancer Institute, University of Alberta, Canada.

Lenalidomide is an important component of initial therapy in newly-diagnosed multiple myeloma, either as maintenance therapy post-autologous stem cell transplantation (ASCT) or as first-line therapy with dexamethasone for patients' ineligible for ASCT (non-ASCT). This retrospective study investigated treatment patterns and outcomes for ASCT-eligible and -ineligible patients who relapsed after lenalidomide as part of first-line therapy, based on data from the Canadian Myeloma Research Group Database for patients treated between January 2007 and April 2019. Among 256 patients who progressed on lenalidomide maintenance therapy, 28. Read More

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Daratumumab provides a survival benefit in relapsed and refractory Multiple Myeloma, independent of baseline clinical characteristics: A meta-analysis.

Pharmacol Res Perspect 2021 Aug;9(4):e00797

Radiology Department, The People's Hospital of Pingyi County, Linyi, China.

Daratumumab was approved in patients with relapsed or refractory multiple myeloma (MM) who previously received proteasome inhibitors or immunomodulatory drugs. However, the efficacy and safety of the addition of daratumumab in subpopulations of patients with relapsed or refractory MM is still unknown. We systematically searched MEDLINE, EMBASE, and Cochrane for randomized controlled trials (inception to September 2020). Read More

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Prognostic impact of resistance to bortezomib and/or lenalidomide in carfilzomib-based therapies for relapsed/refractory multiple myeloma: The Kyoto Clinical Hematology Study Group, multicenter, pilot, prospective, observational study in Asian patients.

Cancer Rep (Hoboken) 2021 Jun 14:e1476. Epub 2021 Jun 14.

Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Background: Combinatory strategies with carfilzomib (CFZ), a second-generation proteasome inhibitor, plus dexamethasone (DEX) with or without lenalidomide (LEN) have shown promising efficacy for patients with relapsed/refractory multiple myeloma (RRMM) in pivotal clinical trials. However, their effects on patients who were resistance to bortezomib (BTZ) and/or LEN have not been fully evaluated in a daily practice setting.

Aims: To evaluate the real-world efficacy and safety of CFZ-based treatments; that is, CFZ with LEN plus DEX (KRD therapy) and CFZ with DEX (KD therapy), in Asian patients, we conducted a multicenter pilot prospective observational study in the Kyoto Clinical Hematology Study Group. Read More

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Development of Agonist-Based PROTACs Targeting Liver X Receptor.

Front Chem 2021 26;9:674967. Epub 2021 May 26.

Division of Organic Chemistry, National Institute of Health Sciences, Kanagawa, Japan.

Liver X receptors (LXRs) belong to the nuclear hormone receptor superfamily and function as ligand-dependent transcription factors that regulate cholesterol homeostasis, lipid homeostasis, and immune responses. LXR antagonists are promising treatments for hypercholesterolemia and diabetes. However, effective LXR antagonists and inhibitors are yet to be developed. Read More

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Venetoclax for the Treatment of Multiple Myeloma: Outcomes Outside of Clinical Trials.

Am J Hematol 2021 Jun 11. Epub 2021 Jun 11.

Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester.

Introduction: Multiple myeloma (MM) remains an incurable disease despite incorporation of novel agents. Venetoclax, a B-cell lymphoma 2 (BCL-2) inhibitor is approved for some hematologic malignancies but not yet for MM, although clinical trials have shown efficacy in patients with MM particularly those harboring t(11;14).

Methods: We reviewed the medical records of relapsed and/or refractory MM patients to study the efficacy and safety of venetoclax used outside of clinical trials at Mayo Clinic between December 2016 and March 2019. Read More

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Efficacy of Qingre Huayu Fang on atherosclerotic vulnerable plaque in apolipoprotein E knockout mice: proteasome pathway involvement.

J Tradit Chin Med 2021 Jun;41(3):432-437

Department of Cardiology, Guizhou Provincial People's Hospital, Guiyang 520000, China.

Objective: To investigate the efficacy and mechanism of the Qingre Huayu Fang () on atherosclerotic vulnerable plaque in apolipoprotein E (ApoE) knockout mice through the ubiquitin proteasome pathway.

Methods: Sixty 8-week-old C57BL/6J ApoE knockout mice were fed a high-fat for 12 weeks and randomly divided into four treatment groups (n = 15 each): high-fat control, bortezomib (a proteasome inhibitor), bortezomib combined with Qingre Huayu Fang, and Qingre Huayu Fang alone. Aortic sections were examined for plaque development, inflammatory cell infiltration, type Ⅰ/Ⅲ collagen expression and immunohistochemical staining of CD40L, nuclear factor-kappa B (NF-κB)/P65 and ubiquitin. Read More

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Exploring the role and clinical implications of proteasome inhibition in medulloblastoma.

Pediatr Blood Cancer 2021 Jun 11:e29168. Epub 2021 Jun 11.

Department of Neurology, University of California, Irvine, California, USA.

Ubiquitin proteasome-mediated protein degradation has been implicated in posttranslational oncogenesis in medulloblastoma. Current research is evaluating the clinical implications of proteasome inhibition as a therapeutic target. In medulloblastoma cell lines, proteasome inhibitors induce apoptosis and inhibit cell proliferation via multiple pathways involving activation of caspase pathways, NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway inhibition, reduced AKT/mTOR pathway activity, and pro-apoptotic protein expression. Read More

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Final Overall Survival Analysis of the TOURMALINE-MM1 Phase III Trial of Ixazomib, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma.

J Clin Oncol 2021 Jun 11:JCO2100972. Epub 2021 Jun 11.

University Hospital Hôtel Dieu, Nantes, France.

Purpose: The double-blind, placebo-controlled, phase III TOURMALINE-MM1 study demonstrated a statistically significant improvement in progression-free survival with ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) versus placebo-Rd in patients with relapsed or refractory multiple myeloma. We report the final analyses for overall survival (OS).

Patients And Methods: Patients were randomly assigned to ixazomib-Rd (n = 360) or placebo-Rd (n = 362), stratified by number of prior therapies (1 2 or 3), previous proteasome inhibitor (PI) exposure (yes no), and International Staging System disease stage (I or II III). Read More

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Ubiquitination and degradation of NF90 by Tim-3 inhibits antiviral innate immunity.

Elife 2021 Jun 10;10. Epub 2021 Jun 10.

Immunology, Beijing Institute of Basic and Medical Sciences, Beijing, China.

Nuclear Factor 90 (NF90) is a novel virus sensor that serves to initiate antiviral innate immunity by triggering the stress granules (SGs) formation. However, the regulation of the NF90-SGs pathway remain largely unclear. We found that Tim-3, an immune checkpoint inhibitor, promotes the ubiquitination and degradation of NF90 and inhibits NF90-SGs mediated antiviral immunity. Read More

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[Current status and future prospects of immunotherapy for multiple myeloma].

Authors:
Yoichi Imai

Rinsho Ketsueki 2021 ;62(5):407-417

IMSUT Hospital, The Institute of Medical Science, The University of Tokyo.

The introduction of autologous stem cell transplantation, proteasome inhibitors, and immunomodulatory drugs (IMiDs) has improved the treatment outcome for multiple myeloma (MM). However, many patients develop resistance to existing therapies, and novel treatment strategies for these patients must be established. Therapeutic antibodies including daratumumab targeting CD38 and elotuzumab targeting SLAMF7 have been introduced in the clinic as immunotherapies for MM. Read More

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Proteomics identify nuclear export as a targetable pathway in neuroblastoma: Comment on "XPO1 inhibition with selinexor synergizes with proteasome inhibition in neuroblastoma by targeting nuclear export of IκB".

Authors:
Nilay Shah

Transl Oncol 2021 Jun 6;14(8):101150. Epub 2021 Jun 6.

Nationwide Children's Hospital, Department of Pediatric Hematology Oncology and Bone Marrow Transplants: Nationwide Children's Hospital Hematology Oncology & Blood and Marrow Transplant, USA.

Neuroblastoma (NBL) is an embryonal malignancy of childhood with poor outcomes for patient with high-risk disease. Multimodal treatment approaches have improved outcomes but at the cost of significant toxicity, and there is no durable therapeutic approach for relapsed disease. As NBL has no singular oncogenic driver, targeted therapeutic options have been limited. Read More

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USP28 promotes aerobic glycolysis of colorectal cancer by increasing stability of FOXC1.

Acta Biochim Pol 2021 Jun 9. Epub 2021 Jun 9.

Department of Anorectal Surgery, First People's Hospital of Yuhang District, Hangzhou, Hangzhou City, Zhejiang Province, 311100, P.R. China.

Aerobic glycolysis is essential for cancer cell metabolism and growth. Deubiquitinase, USP28 (ubiquitin specific peptidase 28), could maintain stability of proteins involved in tumor progression. This study was performed to investigate the role of USP28 in aerobic glycolysis of colorectal cancer. Read More

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Tomato chlorosis virus-encoded p22 suppresses auxin signalling to promote infection via interference with SKP1-Cullin-F-box complex assembly.

Plant Cell Environ 2021 Jun 8. Epub 2021 Jun 8.

State Key Laboratory for Agro-Biotechnology, and Ministry of Agriculture and Rural Affairs, Key Laboratory for Pest Monitoring and Green Management, Department of Plant Pathology, China Agricultural University, Beijing, China.

Phytohormone auxin plays a fundamental role in plant growth and defense against pathogens. However, how auxin signalling is regulated during virus infection in plants remains largely unknown. Auxin/indole-3-acetic acid (Aux/IAA) is the repressor of auxin signalling and can be recognized by an F-box protein transport inhibitor response 1 (TIR1). Read More

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The role of idecabtagene vicleucel in patients with heavily pretreated refractory multiple myeloma.

Ther Adv Hematol 2021 31;12:20406207211019622. Epub 2021 May 31.

Clinical Hematology Department and Clinical Trial Unit, Institut Català d'Oncologia at Hospital Germans Trias i Pujol, Badalona, Spain.

The development of several treatment options over the last 2 decades has led to a notable improvement in the survival of patients with multiple myeloma. Despite these advances, the disease remains incurable for most patients. Moreover, standard combinations of alkylating agents, immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies targeting CD38 and corticoids are exhausted relatively fast in a proportion of high-risk patients. Read More

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Belantamab Mafodotin for the Treatment of Multiple Myeloma: An Overview of the Clinical Efficacy and Safety.

Drug Des Devel Ther 2021 2;15:2401-2415. Epub 2021 Jun 2.

Clinica di Ematologia Azienda Ospedaliero-Universitaria, Ospedali Riuniti di Ancona, Ancona, Italy.

Despite the introduction of immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and, more recently, monoclonal antibodies (mAbs), in the chemotherapy regimens for newly diagnosed (NDMM) and relapsed/refractory MM (RRMM), the occurrence of drug resistance remains a challenge in MM patients. This is mainly in the advanced stage of the disease when treatments are limited, and the prognosis is abysmal. Nevertheless, novel molecules and therapeutic approaches are rapidly moving through the several phases of drug development and could address the need for new treatment options. Read More

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Tetramethylpyrazine Improves Cognitive Function of Alzheimer's Disease Mice by Regulating SSTR4 Ubiquitination.

Drug Des Devel Ther 2021 1;15:2385-2399. Epub 2021 Jun 1.

Department of Neurology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, Hainan, People's Republic of China.

Purpose: Many researches have investigated the functions of tetramethylpyrazine (TMP) in Alzheimer's disease (AD). This study aimed to discuss the underlying mechanism of TMP in AD mice.

Methods: TMP (200 mg/kg) was administered to 6-month-old APP/PS1 transgenic mice, and behavioral changes and hippocampal nerve injury in AD mice were detected. Read More

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Hyperbaric oxygen suppressed tumor progression through the improvement of tumor hypoxia and induction of tumor apoptosis in A549-cell-transferred lung cancer.

Sci Rep 2021 Jun 8;11(1):12033. Epub 2021 Jun 8.

Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, ROC.

Tumor cells have long been recognized as a relative contraindication to hyperbaric oxygen treatment (HBOT) since HBOT might enhance progressive cancer growth. However, in an oxygen deficit condition, tumor cells are more progressive and can be metastatic. HBOT increasing in oxygen partial pressure may benefit tumor suppression. Read More

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Brefeldin A Induces Apoptosis, Inhibits BCR-ABL Activation, and Triggers BCR-ABL Degradation in Chronic Myeloid Leukemia K562 Cells.

Anticancer Agents Med Chem 2021 Jun 8. Epub 2021 Jun 8.

Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.

Background: Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by BCR-ABL oncoprotein. Tyrosine kinase inhibitors have been developed to inhibit the activity of BCR-ABL; however, drug resistance and side effect occur in clinic application. Therefore, it is urgent to find novel drugs for CML treatment. Read More

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Targeting NRF2 to treat cancer.

Semin Cancer Biol 2021 Jun 5. Epub 2021 Jun 5.

Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ, 85721, USA. Electronic address:

NRF2 is a basic leucine zipper (bZip) transcription factor that is the master regulator of redox homeostasis. Under basal conditions, the cellular level of NRF2 is low due to a posttranslational regulation by the ubiquitin proteasome system (UPS). But, when an organism is challenged with oxidative or xenobiotic stress, the NRF2 pathway is activated by inhibition of the E3 ubiquitin ligase complex that normally marks NRF2 for destruction. Read More

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Protease-activated receptor 2 stabilizes Bcl-xL and regulates EGFR-targeted therapy response in colorectal cancer.

Cancer Lett 2021 Jun 10;517:14-23. Epub 2021 Jun 10.

State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. Electronic address:

The Bcl-2 homolog Bcl-xL is emerging as a key factor in tumorigenesis due to its prominent pro-survival and cell death-independent functions. However, the regulation of Bcl-xL by microenvironment and its implication in cancer therapy of colorectal carcinoma (CRC) are unclear. Here, we demonstrated that Bcl-xL expression was positively associated with protease-activated receptor 2 (PAR2) in CRC. Read More

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Anti-plasma cell treatment in refractory autoimmune hemolytic anemia in a child with multivisceral transplant.

Pediatr Transplant 2021 Jun 6:e14045. Epub 2021 Jun 6.

MedStar Georgetown University Hospital, Transplant Institute, Washington, DC, USA.

Background: Warm-antibody AIHA is known to complicate solid organ (SOT) and HSCT, the disease maybe refractory to standard therapy. Immunosuppressive therapies as well as IVIG, and rituximab have been the main stay of treatment. Over the past decade, B-lymphocyte targeted, anti-CD-20 antibody has been recognized in the treatment of autoimmune diseases and utilized in AIHA. Read More

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Progress and challenges in the treatment of cardiac amyloidosis: a review of the literature.

ESC Heart Fail 2021 Jun 5. Epub 2021 Jun 5.

Department of Cardiology, Emergency Institute for Cardiovascular Diseases 'Prof. Dr. C. C. Iliescu', 3rd Cardiology Department, 258 Fundeni Street, Bucharest, 022328, Romania.

Cardiac amyloidosis is a restrictive cardiomyopathy determined by the accumulation of amyloid, which is represented by misfolded protein fragments in the cardiac extracellular space. The main classification of systemic amyloidosis is determined by the amyloid precursor proteins causing a very heterogeneous disease spectrum, but the main types of amyloidosis involving the heart are light chain (AL) and transthyretin amyloidosis (ATTR). AL, in which the amyloid precursor is represented by misfolded immunoglobulin light chains, can involve almost any system carrying the worst prognosis among amyloidosis patients. Read More

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Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial.

Lancet Oncol 2021 06;22(6):801-812

Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, Netherlands.

Background: In a phase 1b study, intravenous daratumumab plus pomalidomide and dexamethasone induced a very good partial response or better rate of 42% and was well tolerated in patients with heavily pretreated multiple myeloma. We aimed to evaluate whether daratumumab plus pomalidomide and dexamethasone would improve progression-free survival versus pomalidomide and dexamethasone alone in patients with previously treated multiple myeloma.

Methods: In this ongoing, open-label, randomised, phase 3 trial (APOLLO) done at 48 academic centres and hospitals across 12 European countries, eligible patients were aged 18 years or older, had relapsed or refractory multiple myeloma with measurable disease, had an Eastern Cooperative Oncology Group performance status of 0-2, had at least one previous line of therapy, including lenalidomide and a proteasome inhibitor, had a partial response or better to one or more previous lines of antimyeloma therapy, and were refractory to lenalidomide if only one previous line of therapy was received. Read More

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Transmembrane protein 168 mutation reduces cardiomyocyte cell surface expression of Nav1.5 through αB-crystallin intracellular dynamics.

J Biochem 2021 Jun 4. Epub 2021 Jun 4.

Division of Molecular Medical Biochemistry, Department of Biochemistry and Molecular Biology, Shiga University of Medical Science.

Transmembrane protein 168 (TMEM168) was found to be localized on the nuclear membrane. A heterozygous mutation (c.1616G>A, p. Read More

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Phytochemical library screen reveals betulinic acid as a novel Skp2-SCF E3 ligase inhibitor in non-small cell lung cancer.

Cancer Sci 2021 Jun 3. Epub 2021 Jun 3.

Institute of Clinical Pharmacology, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.

Skp2 is overexpressed in multiple cancers and plays a critical role in tumor development through ubiquitin/proteasome-dependent degradation of its substrate proteins. Drugs targeting Skp2 have exhibited promising anticancer activity. Here, we identified a plant-derived Skp2 inhibitor, betulinic acid (BA), via high-throughput structure-based virtual screening of a phytochemical library. Read More

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Propensity-score matched analysis of the efficacy of maintenance/continuous therapy in newly diagnosed patients with multiple myeloma: a multicenter retrospective collaborative study of the Japanese Society of Myeloma.

J Cancer Res Clin Oncol 2021 Jun 2. Epub 2021 Jun 2.

Department of Hematology/Oncology, Higashi Nagoya National Hospital, Nagoya, Japan.

Background: Maintenance ± consolidation or continuous therapy is considered a standard of care for both transplant-eligible and -ineligible patients with multiple myeloma (MM). However, long-term benefits of such therapy have not yet been clarified in the context of clinical practice.

Purpose: To clarify the efficacy of maintenance/continuous approach, we retrospectively analyzed the cohort data of newly diagnosed MM patients by propensity-score matching based on age, gender, revised International Staging System (R-ISS) stage, and implementation of transplantation to reduce the bias due to confounding variables. Read More

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Bortezomib for anti-NMDAR encephalitis following daclizumab treatment in a patient with multiple sclerosis.

BMJ Neurol Open 2021 18;3(1):e000096. Epub 2021 May 18.

NIHR Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UK.

Background: Daclizumab is an anti-CD25 monoclonal antibody developed for the treatment of relapsing remitting multiple sclerosis, which was withdrawn worldwide in March 2018, due to emerging serious immune-mediated systemic andcentral nervous system adverse events. We report a case of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis occurring 14 weeks after stopping daclizumab, which responded to the proteasome inhibitor bortezomib.

Methods: Following lack of effective clinical response to first line (corticosteroid, plasma exchange, intravenous immunoglobulin) and second line (rituximab) treatments, bortezomib therapy was commenced. Read More

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UBE4B, a microRNA-9 target gene, promotes autophagy-mediated Tau degradation.

Nat Commun 2021 06 2;12(1):3291. Epub 2021 Jun 2.

Metabolism and Neurophysiology Research Group, KRIBB, Daejeon, Korea.

The formation of hyperphosphorylated intracellular Tau tangles in the brain is a hallmark of Alzheimer's disease (AD). Tau hyperphosphorylation destabilizes microtubules, promoting neurodegeneration in AD patients. To identify suppressors of tau-mediated AD, we perform a screen using a microRNA (miR) library in Drosophila and identify the miR-9 family as suppressors of human tau overexpression phenotypes. Read More

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The nonreceptor tyrosine kinase SRMS inhibits autophagy and promotes tumor growth by phosphorylating the scaffolding protein FKBP51.

PLoS Biol 2021 Jun 2;19(6):e3001281. Epub 2021 Jun 2.

Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.

Nutrient-responsive protein kinases control the balance between anabolic growth and catabolic processes such as autophagy. Aberrant regulation of these kinases is a major cause of human disease. We report here that the vertebrate nonreceptor tyrosine kinase Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites (SRMS) inhibits autophagy and promotes growth in a nutrient-responsive manner. Read More

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