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Chemo-RaST with bortezomib inhibits multiple myeloma relapse.

Rationale: Multiple myeloma (MM) is a hematological malignancy with a high relapse rate that ultimately leads to patient mortality. Current therapies often fail to achieve sustained remission due to adaptation of clonally heterogeneous tumor populations. We hypothesized that Chemo-RaST, a therapeutic strategy combining bortezomib with ⁸⁹Zr-daratumumab-mediated radionuclide dynamic therapy (RaST), would synergize photophysical generation of cytotoxic reactive oxygen species (ROS) with mitochondrial ROS induction to block clonal adaptation and prevent MM relapse. Methods: We evaluated chemo-RaST

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… Stock was mixed vigorously with Tf in phosphate-buffered saline (PBS) at a 1:3 TiO 2 :Tf mass ratio and dispersed by probe sonication (3 W, 60 s; Cole-Parmer Ultrasonic Processor GE 130PB (Vernon Hills, IL)). …

Targeting HLA-E in Lung Cancer: The Therapeutic Potential of IRF5-Engineered M1-Macrophage-Derived Exosomes.

Immunotherapy is a pivotal approach in the treatment of lung cancer. Although HLA-E is a potential target for tumor immunotherapy, its role in lung cancer remains unclear. Previous studies have identified the transcription factor IRF5 as a characteristic gene of M1-like macrophages, highlighting its crucial role in promoting antitumor immune responses. In this study, we developed an engineered M1-like macrophage exosomes expressing IRF5 (IRF5 M1-exos) and demonstrated their ability to inhibit proliferation, migration, and invasion of lung cancer cells. Moreover, our experiments using a nude mo

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… The resulting pellet was resuspended in nuclear lysis buffer (50‐mM Tris–HCl pH 8 0.1, 10‐mM EDTA,1% SDS supplemented with protease inhibitors; volume: 500 μL per every one million cells), followed by sonication for 10 cycles consisting of alternating periods of 30 s on and 30 s off for each cycle. …

Deciphering the Causal Relationship between Sodium-glucose Cotransporter 2 Inhibition and Cancer Risks: A Comprehensive Mendelian Randomization Study.

Background: Controversy persists regarding the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cancer. The underlying causal relationship remains unclear. Method: A two-sample Mendelian randomization (MR) strategy was employed to investigate the causal associations between SGLT2 inhibitors and 26 site-specific malignancies. Instrumental variants strongly associated with SLC5A2 gene expression and glycated hemoglobin A1c levels were identified as the genetic proxy for SGLT2 inhibition. Cancer-related outcome datasets sourced from the OpenGWAS project were separated into discover

Hyaluronan, fluid pressure, and stromal resistance in pancreas cancer.

Pancreatic ductal adenocarcinomas (PDAs) are notoriously aggressive and resistant to treatment. They distinguish themselves further by their robust fibroinflammatory, or desmoplastic, stromal reaction and degree of hypovascularity. Recent findings have revealed multiple mechanisms of stromal complicity in disease pathogenesis and resistance. In this review, we focus on altered physicomechanics as one mechanism of what we term as 'stromal resistance' in PDA. Extremely high interstitial fluid pressures and a dense extracellular matrix combine to limit the delivery and distribution of therapeutic

A dual-mechanism model of Selinexor in DLBCL: p53 reactivation and metabolic reprogramming.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy with limited therapeutic options in the relapsed or refractory setting. Selinexor, a selective inhibitor of nuclear export targeting XPO1, has demonstrated clinical activity in DLBCL. However, the molecular mechanisms underlying its antitumor effects remain incompletely defined. METHODS: We evaluated the clinical efficacy of Selinexor in a real-world cohort of lymphoma patients and performed integrative transcriptomic and proteomic analyses in DLBCL cell models representing germinal center B-cell–like (GCB) and non-G

The Role of Radiosensitizing Drugs in Osteosarcoma Treatment: Mechanisms and Clinical Perspectives.

Osteosarcoma is a highly malignant bone tumor that is resistant to radiotherapy and is associated with poor treatment outcomes and prognoses. Understanding the mechanisms of radioresistance and finding strategies to enhance the radiosensitivity is crucial for improving clinical efficacy. The aim of this review was to address the approaches for enhancing the efficacy of radiotherapy in osteosarcoma, thereby improving patient outcomes. Specifically, we have focused on the mechanisms of radiosensitization and the relationship between drugs that enhance radiosensitivity and cancer. These mechanism

A novel mechanism in regulating drug sensitivity, growth, and apoptosis of bortezomib-resistant multiple myeloma cells: the USP4/KLF2/HMGA2 cascade.

BackgroundMultiple myeloma (MM) is a malignant disorder originating from plasma cells. Bortezomib (BTZ) resistance has become a huge obstacle to MM treatment. Herein, we elucidated the action of Kruppel-like factor 2 (KLF2), a crucial transcription factor (TF), on BTZ resistance of MM.MethodsTwo BTZ-resistant cell lines (MM1.S/BTZ and NCI-H929/BTZ) were generated and used. KLF2 mRNA was quantified by quantitative PCR, and protein expression was analyzed by immunoblotting. MTT cell cytotoxicity assay was used to test BTZ sensitivity. Cell growth was detected by MTT and EdU assays. Flow cytometr

Иммунорегулирующий амфипатический песптид, полученный из молекулы защиты фасиолы гепатики (FhHDM-1.C2), демонстрирует мощную биотерапевтическую активность в мусриновой модели множественного склероза.

Молекулярные защитные молекулы (HDM) — семейство иммунных регуляционных пептидов, которые выражаются исключительно триматодными червями. Ранее мы продемонстрировали, что в vivo FhHDM-1, архетипный член HDM, регулировала макрофагическую реакцию на подстрекательские лиганды, тем самым облегчая процесс повреждения иммунной ткани в нескольких мусриновых моделях воспалительных заболеваний. Соответственно, мы исходили из того, что понимание взаимосвязи между структурой и функцией НДМ облегчило бы идентификацию минимального биоактивного пептида, который представлял бы собой более синтезируемый, эконо

Lambda-free light chain: A serum marker of dengue disease via NS3 protease-mediated antibody cleavage.

Dengue poses a significant global public health threat, with diverse clinical manifestations due to complex interactions between the host and the pathogen. Recent reports have highlighted elevated serum-free light chain (FLC) levels in viral infectious diseases. Hence, our study aimed to investigate serum FLC levels in dengue patients. The findings revealed elevated serum λ FLCs, which were associated with the severity of dengue. Receiver operating characteristic curve (ROC) analysis demonstrated that λ FLCs may serve as a serum marker for identifying dengue disease (AUC: 0.7825, sensitivity:

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… The cells were lysed by sonication, and the pellet and supernatant were separated by centrifugation at 12,000 rpm for 20 minutes. For protein purification, the supernatant was incubated with Ni-NTA resin (Cat. No: 30210, QIAGEN) for 1 hour at 4°C. …

CXCL12/CXCR4 axis supports mitochondrial trafficking in tumor myeloma microenvironment.

Mesenchymal stromal cells (MSCs) within the protective microenvironment of multiple myeloma (MM) promote tumor growth, confer chemoresistance and support metabolic needs of plasma cells (PCs) even transferring mitochondria. In this scenario, heterocellular communication and dysregulation of critical signaling axes are among the major contributors to progression and treatment failure. Here, we report that myeloma MSCs have decreased reliance on mitochondrial metabolism as compared to healthy MSCs and increased tendency to deliver mitochondria to MM cells, suggesting that this intercellular exch

CPUY201112, a novel synthetic small-molecule compound and inhibitor of heat shock protein Hsp90, induces p53-mediated apoptosis in MCF-7 cells.

Heat-shock protein 90 (Hsp90) is highly expressed in many tumor cells and is associated with the maintenance of malignant phenotypes. Targeting Hsp90 has had therapeutic success in both solid and hematological malignancies, which has inspired more studies to identify new Hsp90 inhibitors with improved clinical efficacy. Using a fragment-based approach and subsequent structural optimization guided by medicinal chemistry principles, we identified the novel compound CPUY201112 as a potent Hsp90 inhibitor. It binds to the ATP-binding pocket of Hsp90 with a kinetic dissociation (Kd) constant of 27

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… Cells were harvested after 20 h of growth at 16 °C and then disrupted by sonication. …

Targeting Selectins and Their Ligands in Cancer.

Aberrant glycosylation is a hallmark of cancer cells with increased evidence pointing to a role in tumor progression. In particular, aberrant sialylation of glycoproteins and glycolipids has been linked to increased immune cell evasion, drug evasion, drug resistance, tumor invasiveness, and vascular dissemination, leading to metastases. Hypersialylation of cancer cells is largely the result of overexpression of sialyltransferases (STs). Differentially, humans express twenty different STs in a tissue-specific manner, each of which catalyzes the attachment of sialic acids via different glycosidi

Effects of Carbon Nanomaterials and Aloe vera on Melanomas-Where Are We? Recent Updates.

Melanoma is an aggressive skin cancer that affects approximately 140,000 people worldwide each year, with a high fatality rate. Available treatment modalities show limited efficacy in more severe cases. Hence, the search for new treatment modalities, including immunotherapies, for curing, mitigating, and/or preventing cancer is important and urgently needed. Carbon nanoparticles associated with some plant materials, such as Aloe vera, have shown appealing antineoplastic activity, derived mainly from the compounds aloin, aloe-emodin, barbaloin acemannan, and octapeptide, thus representing new p

Recent Advances in Understanding the Mechanisms of Elemene in Reversing Drug Resistance in Tumor Cells: A Review.

Malignant tumors are life-threatening, and chemotherapy is one of the common treatment methods. However, there are often many factors that contribute to the failure of chemotherapy. The multidrug resistance of cancer cells during chemotherapy has been reported, since tumor cells' sensitivity decreases over time. To overcome these problems, extensive studies have been conducted to reverse drug resistance in tumor cells. Elemene, an extract of the natural drug Curcuma wenyujin, has been found to reverse drug resistance and sensitize cancer cells to chemotherapy. Mechanisms by which elemene rever

Tumor-derived systems as novel biomedical tools-turning the enemy into an ally.

Cancer is a complex illness that presents significant challenges in its understanding and treatment. The classic definition, "a group of diseases characterized by the uncontrolled growth and spread of abnormal cells in the body," fails to convey the intricate interaction between the many entities involved in cancer. Recent advancements in the field of cancer research have shed light on the role played by individual cancer cells and the tumor microenvironment as a whole in tumor development and progression. This breakthrough enables the utilization of the tumor and its components as biological

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… Other reported methods to coat CCM include sonication (after prior incubation) and microfluidic-assisted nanoparticle coating. … EVs can be passively loaded using saponin-based permeabilization, electroporation (ideal for siRNA or miRNA loading), and mechanical methods, such as freeze‒thawing, sonication, and extrusion [ 152 ]. …

Реактивность антител против EBNA1 и GlialCAM отличает пациентов с множественным склерозом от здорового контроля.

Множественный склероз (MS) — аутоиммунное демиелионирующее расстройство центральной нервной системы (CNS), которое связано с вирусом Эпштейн-Барр (EBV) перед заболеванием. Молекулярные механизмы, лежащие в основе этой связи, понимаются лишь частично. Ранее мы описали молекулярную анимацию между коэффициентом транскрипции EBV ядерный антиген 1 (EBNA1) и тремя человеческими белками CNS: аноктамином-2 (ANO2), альфа-B кристаллом (CRYAB) и молекулой глиального сцепления клеток (GlialCAM). Здесь мы изучили антителные реакции на EBNA1 и GlialCAM в большой группе из 650 пациентов MS и 661 популяционны

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… Cells were cultured to a density of 3 × 10^6 cells/mL, lysed via sonication, and his-tagged proteins were purified with Ni-INDIGO resin (Cube Biotech 75103), followed by size-exclusion chromatography on a Superdex 75 Increase 10/300 GL column (Cytiva 29148721). …

The reporting quality and transparency of orthopaedic studies using Bayesian analysis requires improvement: A systematic review.

BackgroundBayesian methods are being used more frequently in orthopaedics. To advance the use and transparent reporting of Bayesian studies, reporting guidelines have been recommended. There is currently little known about the use or applications of Bayesian analysis in orthopedics including adherence to recommended reporting guidelines. The objective is to investigate the reporting of Bayesian analysis in orthopedic surgery studies; specifically, to evaluate if these papers adhere to reporting guidelines.MethodsWe searched PUBMED to December 2nd, 2020. Two reviewers independently identified s

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… Knee Surg Sports Traumatol Arthrosc 29:1850–1861. https://doi.org/10.1007/s00167-020-06231-x Yan Q, Karau MJ, Greenwood-Quaintance KE et al. (2018) Comparison of Diagnostic Accuracy of Periprosthetic Tissue Culture in Blood Culture Bottles to That of Prosthesis Sonication Fluid Culture for Diagnosis …

Acupuncture Synergized With Bortezomib Improves Survival of Multiple Myeloma Mice via Decreasing Metabolic Ornithine.

Multiple myeloma (MM) is a hematological malignancy worldwide in urgent need for novel therapeutic strategies. Since Velcade (bortezomib) was approved for the treatment of relapsed/refractory MM in 2003, we have seen considerable improvement in extending MM patient survival. However, most patients are fraught with high recurrence rate and incurability. Acupuncture is known for alleviating patient symptoms and improving the quality of life, but it is not well investigated in MM, especially in combination with bortezomib. In this study, we employed LC-MS and UHPLC-MS together with bioinformatics

Discovery and validation of surface N-glycoproteins in MM cell lines and patient samples uncovers immunotherapy targets.

BackgroundMultiple myeloma (MM) is characterized by clonal expansion of malignant plasma cells in the bone marrow. While recent advances in treatment for MM have improved patient outcomes, the 5-year survival rate remains ~50%. A better understanding of the MM cell surface proteome could facilitate development of new directed therapies and assist in stratification and monitoring of patient outcomes.MethodsIn this study, we first used a mass spectrometry (MS)-based discovery-driven cell surface capture (CSC) approach to map the cell surface N-glycoproteome of MM cell lines. Next, we developed t

Non-canonical NFκB mutations reinforce pro-survival TNF response in multiple myeloma through an autoregulatory RelB:p50 NFκB pathway.

Environmental drug resistance constitutes a serious impediment for therapeutic intervention in multiple myeloma. Tumor-promoting cytokines, such as tumor necrosis factor (TNF), induce nuclear factor-κB (NFκB)- driven expression of pro-survival factors, which confer resistance in myeloma cells to apoptotic insults from TNF-related apoptosis-inducing ligand (TRAIL) and other chemotherapeutic drugs. It is thought that RelA:p50 dimer, activated from IκBα-inhibited complex in response to TNF-induced canonical NFκB signal, mediates the pro-survival NFκB function in cancerous cells. Myeloma cells add