Endocrine system-related adverse events associated with PD-1/PD-L1 inhibitors: data mining from the FDA adverse event reporting system.

Background: Various immune checkpoint inhibitors, such as programmed cell death protein-1 (PD-1) and its ligand (PD-L1), have been approved for use, but they have side effects on the endocrine glands. Methods: Adverse event reports related to PD-1/PD-L1 inhibitors from the FDA Adverse Event Reporting System (FAERS) from the first quarter of 2019 to the first quarter of 2023 were extracted, and the reported Odds ratio methods (ROR method) and comprehensive standard methods (MHRA methods) were used for data mining and analysis. Results: A total of 5,322 reports (accounts for 6.68% of the total reports)of AEs in endocrine system were collected, including 1852 of pabolizumab (34.80%), 2,326 of navuliumab (43.71%), 54 of cimipriliumab (1.01%), 800 of atilizumab (15.03%), 222 of duvariumab (4.17%) and 68 of averumab (1.28%). Endocrine system-related AEs were mainly present in men (excluding those treated with pembrolizumab) aged ≥65 years. The ratio of AEs components in the endocrine system for the six drugs was approximately 3-8%. The main endocrine glands involved in AEs were the thyroid (pembrolizumab), pituitary and adrenal (nivolumab), adrenal (cemiplimab, atezolizumab, and avelumab), and thyroid (durvalumab). Most patients experienced AEs between 30 and 365 (mean, 117) days,the median time was 61d. AEs resulted in prolonged hospitalization in >40% and death in >10% of cases after administration of pembrolizumab, nivolumab, or durvalumab. Conclusion: Men aged ≥65 years should be concerned about endocrine-related AEs. There was a lengthy interval between the use of PD-1/PD-L1 inhibitors and endocrine system-related AEs, but the outcome was serious. Special attention should be given to endocrine system-related AEs when using pembrolizumab, nivolumab, or durvalumab.

A Triazine Membrane for Sustainable Acquisition of Au(III) from Wastewater.

The recovery of Au(III) from solution using adsorbents in the form of granules or powders is challenging due to issues such as instability during the recovery process or mass loss caused by small particle size. This study introduces a PEI-TCT/PVDF composite membrane designed to intercept and capture Au(III) in wastewater. Experimental results demonstrated that the PEI-TCT/PVDF membrane exhibits a broad pH range (1-8) and a high retention efficiency for Au(III) of 97.8%, with a maximum adsorption capacity of 294.5 mg/g. The mechanism of Au(III) adsorption on the PEI-TCT/PVDF membrane was mainly through electrostatic adsorption, which caused AuCl4- to aggregate on the surface of the membrane and gradually reduced to Au0 and Au+. Furthermore, the membrane can be entirely regenerated within 20 min and maintains its performance in subsequent adsorption cycles. This study highlights the potential of PEI-TCT/PVDF membranes for the recovery of precious Au(III).

Epilepsy-associated genes: an update.

PURPOSE: To provide an updated list of epilepsy-associated genes based on clinical-genetic evidence. METHODS: Epilepsy-associated genes were systematically searched and cross-checked from the OMIM, HGMD, and PubMed databases up to July 2023. To facilitate the reference for the epilepsy-associated genes that are potentially common in clinical practice, the epilepsy-associated genes were ranked by the mutation number in the HGMD database and by case number in the China Epilepsy Gene 1.0 project, which targeted common epilepsy. RESULTS: Based on the OMIM database, 1506 genes were identified to be associated with epilepsy and were classified into three categories according to their potential association with epilepsy or other abnormal phenotypes, including 168 epilepsy genes that were associated with epilepsies as pure or core symptoms, 364 genes that were associated with neurodevelopmental disorders as the main symptom and epilepsy, and 974 epilepsy-related genes that were associated with gross physical/systemic abnormalities accompanied by epilepsy/seizures. Among the epilepsy genes, 115 genes (68.5%) were associated with epileptic encephalopathy. After cross-checking with the HGMD and PubMed databases, an additional 1440 genes were listed as potential epilepsy-associated genes, of which 278 genes have been repeatedly identified variants in patients with epilepsy. The top 100 frequently reported/identified epilepsy-associated genes from the HGMD database and the China Epilepsy Gene 1.0 project were listed, among which 40 genes were identical in both sources. SIGNIFICANCE: Recognition of epilepsy-associated genes will facilitate genetic screening strategies and be helpful for precise molecular diagnosis and treatment of epilepsy in clinical practice.

RING box protein-1(RBX1), a key component of SCF E3 ligase, induced multiple myeloma cell drug-resistance though suppressing p27.

Multiple myeloma (MM) is a clonal disease of plasma cells that remains, for the most part, incurable despite the advent of several novel therapeutics. The elevated expression of p27 and its association with cell-cycle arrest is speculated to be one of the major mechanisms by which MM cells escape the cytotoxic effects of therapeutic agents. In this study, we demonstrated that RBX1 silencing could inhibit MM cell growth and promote cell drug resistance. RBX1 directly interacted with and triggered the ubiquitination and degradation of p27, ultimately causing p27 reduction. Additionally, cell growth and apoptosis analysis indicated that the role of RBX1 in regulating myeloma cell proliferation and drug resistance resulted from p27 accumulation, which occurred in a Thr187 phosphorylation-dependent manner. Furthermore, the cell-cycle analysis demonstrated that RBX1 overexpression induced cells to enter the cell cycle (S-phase) and partially inhibited chemotherapeutic drugs-mediated cell cycle arrest. Notably, the forced expression of RBX1 also inhibited the cell adhesion-mediated elevation of p27 and induced the accumulation of adherent cells in apoptosis, especially the proteolytic cleavage of caspase-3. Additionally, RBX1 knockdown significantly inhibited myeloma development in SCID-Hu mice and in a human MM xenotransplant model. Overall, these in vitro and in vivo experiments indicated that the RBX1-p27 axis could be a central molecular mechanism by which RBX1 functions as a tumor promoter and stimulates cell growth in chemotherapeutic drugs treated MM cells.

AQRS: Anti-quantum ring signature scheme for secure epidemic control with blockchain.

Epidemics, such as Corona Virus Disease 2019 (COVID-19), have serious consequences globally, of which the most effective way to control the infection is contact tracing. Nowadays, research related to privacy-preserving epidemic infection control has been conducted, nevertheless, current researchers do not regard the authenticity of records and infection facts as well as poor traceability. Moreover, with the emergence of quantum computing, there is a bottleneck in upholding privacy, security and efficiency. Our paper proposes a privacy-preserving epidemic infection control scheme through lattice-based linkable ring signature in blockchain, called AQRS. Firstly, our scheme adopts a blockchain with three ledgers to store information in a distributed manner, which offers transparency and immunity from the Single Point of Failure (SPoF) and Denial of Service (DoS) attacks. Moreover, we design a lattice-based linkable ring signature scheme to secure privacy-preserving of epidemic infection control. Significantly, we are the first to introduce the lattice-based linkable ring signature into privacy preserving in epidemic control scenario. Security analysis indicates that our scheme ensures unconditional users anonymity, record unforgeability, signature linkability, link non-slanderability and contact traceability. Finally, the comprehensive performance evaluation demonstrates that our scheme has an efficient time-consuming, storage consumption and system communication overhead and is practical for epidemic and future pandemic privacy-preserving.

Effects of SF6 decomposition components and concentrations on the discharge faults and insulation defects in GIS equipment.

Gas-insulated switchgear (GIS) is widely used across multiple electric stages and different power grid levels. However, the threat from several inevitable faults in the GIS system surrounds us for the safety of electricity use. In order to improve the evaluation ability of GIS system safety, we propose an efficient strategy by using machine learning to conduct SF6 decomposed components analysis (DCA) for further diagnosing discharge fault types in GIS. Note that the empirical probability function of different faults fitted by the Arrhenius chemical reaction model has been investigated into the robust feature engineering for machine learning based GIS diagnosing model. Six machine learning algorithms were used to establish models for the severity of discharge fault and main insulation defects, where identification algorithms were trained by learning the collection dataset composing the concentration of the different gas types (SO2, SOF2, SO2F2, CF4, and CO2, etc.) in the system and their ratios. Notably, multiple discharge fault types coexisting in GIS can be effectively identified based on a probability model. This work would provide a great insight into the development of evaluation and optimization on solving discharge fault in GIS.

Synthesis and characterization of dopamine-modified Ca-alginate/poly(N-isopropylacrylamide) microspheres for water retention and multi-responsive controlled release of agrochemicals.

The multi-responsive controlled-release system could enhance crop yield while improving utilization efficiency of agrochemicals, and minimize environmental pollution caused by agrochemicals overuse. This work reports a novel Ca-alginate/Poly(N-isopropylacrylamide)@polydopamine (Ca-alginate/PNIPAm@PDA) microsphere to control the agrochemicals release. Microsphere with a semi-interpenetrating network, which contained pH-sensitive Ca-alginate, temperature-sensitive poly(N-isopropylacrylamide) (PNIPAm), and sunlight-sensitive polydopamine (PDA), was characterized by thermogravimetric analysis, zeta potential, Fourier transform infrared spectroscopy, and scanning electron microscopy to prove the successful synthesis. Moreover, the comprehensive performances, including photothermal conversion, water absorbency, water retention, and controlled-release agrochemicals behaviors, were systematically investigated. The results indicated that the composite microsphere was a prosperous water and agrochemicals manager to effectively retain water and control the release of agrochemicals by external stimulation. Consequently, the Ca-alginate/PNIPAm@PDA microsphere with outstanding water-retention and controlled-release capacities is economical and eco-friendly and thus is promising for utilization as water and agrochemicals controlled-release carrier material in agriculture applications.

Controllable conversion of Prussian blue@yeast bio-template into 3D cage-like magnetic Fe3O4@N-doped carbon absorbent and its cohesive regeneration by persulfate activation.

A multitude of heteroatom-doped carbon adsorbents have been explored to cope with ever-growing organic pollution. However, development of these advanced carbon materials with adequate activity and stability remains challenging. Herein, unique 3D cage-like magnetic N-doped Fe3O4@C adsorbents were rationally constructed by a one-step pyrolysis of Prussian blue@yeast (PB@yeast) bio-templates. By using yeast as an available biological support, the prepared Fe3O4@C hybrids were demonstrated to provide a sufficient number of Fe, N and C atoms for the novel cage-like microstructures, making them a new type of Fe, N co-doped carbon absorbents with a facile preparation procedure and remarkable adsorption behavior. Rhodamine B (RhB) removal indicated that the prepared N-doped Fe3O4@C adsorbents displayed high adsorption capabilities in a near-neutral solution, and Fe3O4@C (1 : 0.11) exhibited a maximum adsorption capability of 257.06 mg g-1. More importantly, spent N-doped Fe3O4@C absorbents, which could be recovered by magnetic separation and cohesive persulfate (PS) activated photo-Fenton regeneration, showed excellent adsorption reusability and high stability even after 5 cycles. Overall, this paper presents a simple method for fabrication of a 3D cage-like magnetic N-doped Fe3O4@C adsorbent, which provides a significant guidance for the study of Fe, N co-doped carbon adsorbents towards dye wastewater treatment.

Fabrication of detonation nanodiamond@sodium alginate hydrogel beads and their performance in sunlight-triggered water release.

Agricultural water use accounts for around 70% of total water use in the world. Enhancing agricultural water use efficiency is a key way to cope with water shortage. Here, sunlight-responsive hydrogel beads consisting of sodium alginate (SA) matrix and detonation nanodiamond (DND) were fabricated by an ion gelation technique, which has potential applications in controlled water release. The interaction between the DND and SA matrix was investigated by Fourier transform infrared (FTIR) spectra and X-ray diffraction (XRD). UV-vis diffuse reflectance spectra verified DND can absorb solar energy in the UV, visible and even near-infrared regions. DND dispersed in the hydrogel matrix can absorb sunlight and generate heat, increasing the temperature of the matrix and resulting in slow release of water from the elastic beads. In addition, the effects of DND content and pH were systematically studied to evaluate their water adsorption properties. The swelling kinetics of DND@SA hydrogel beads in distilled water could be fitted well with a pseudo-second-order kinetic model. Six consecutive cycles of water release-reswelling indicated that their easy regeneration and reusability. The novel and eco-friendly hydrogel beads should be applicable to on-demand, sequential, and long-term release of water via light exposure.

Three years of exposure to lead and elevated CO2 affects lead accumulation and leaf defenses in Robinia pseudoacacia L. seedlings.

Few studies have explored the long-term effects of elevated atmospheric CO2 combined with lead (Pb) contamination on plants. The objective of this study was to examine the effects of 3 years of elevated CO2 (700 ±â€¯23 µmol mol-1) on Pb accumulation and plant defenses in leaves of Robinia pseudoacacia L. seedlings in exposed to Pb (500 mg kg-1 soil). Elevated CO2 increased Pb accumulation in leaves and Pb removal rate in soils. In plants exposed to Pb stress, total chlorophyll and carotenoid contents in leaves were lower under elevated CO2 than under ambient CO2, but seedling height and width increased under elevated CO2 relative to ambient CO2. Elevated CO2 significantly (p < .01) stimulated malondialdehyde content in leaves under Pb exposure. Superoxide dismutase and catalase activity increased significantly (p < .01), peroxidase activity decreased significantly (p < .01), and glutathione, cystine, and phytochelatin contents increased under elevated CO2 + Pb relative to Pb alone. Elevated CO2 stimulated the production of soluble sugars, proline, flavonoids, saponins, and phenolics in plants exposed to Pb stress. Ove rall, long-term elevation of CO2 increased Pb-induced oxidative damage in seedlings, but enhanced the phytoextraction of Pb from contaminated soils.

ADP-ribosylation factor 1 (ARF1) takes part in cell proliferation and cell adhesion-mediated drug resistance (CAM-DR).

Cell adhesion-mediated drug resistance (CAM-DR) remains the primary obstacle in human multiple myeloma (MM) therapy. In this study, we aimed at investigating the expression and biologic function of ARF1 in MM. We determined that ARF1 expression was positively correlated with cell proliferation and knockdown of ARF1 contributed to CAM-DR. The enhancement in the adhesion of MM cells to fibronectin (FN) or the bone marrow stroma cell line HS-5 cells translated to an increased CAM-DR phenotype. Importantly, we showed that this CAM-DR phenotype was correlated with the phosphorylation of Akt and ERK in MM cells. Moreover, we sought to determine whether ARF1 could interact with p27 in RPMI8226 cells. Knockdown of ARF1 also significantly decreased pT157-p27 protein expression in RPMI8226 cells. Our research shows ARF1 may reverse CAM-DR by regulating phosphorylation of p27 at T157 in MM. Taken together, our data shed new light on the molecular mechanism of CAM-DR in MM, and targeting ARF1 may be a novel therapeutic approach for improving the effectiveness of chemotherapy in MM.

Expression of far upstream element binding protein 1 in B­cell non­Hodgkin lymphoma is correlated with tumor growth and cell­adhesion mediated drug resistance.

Cell adhesion­mediated drug resistance (CAM­DR) remains a major obstacle to the effectiveness of chemotherapeutic treatment of lymphoma. Far upstream element binding protein 1 (FBP1) is a multifunctional protein that is highly expressed in proliferating cells of several solid neoplasms; however, its expression and biological function in B­cell lymphoma is largely unknown. FBP1 expression in both reactive lymphoid tissues and several B­cell lymphomas, including follicular lymphoma and diffuse large B­cell lymphoma were detected by immunohistochemistry analysis. FBP1 expression in B­cell lymphoma was also associated with poor survival outcomes. Functionally, small interfering RNA­mediated silencing of FBP1 was able to inhibit the proliferation of B­cell lymphoma cells, resulting in G0/G1 phase cell cycle arrest. Furthermore, results of a cell adhesion assay demonstrated that adhesion to fibronectin or bone marrow stromal cells induced FBP1 expression, which in turn facilitated cell adhesion. Finally, FBP1 knockdown reversed CAM­DR. These findings support a role for FBP1 in non­Hodgkin lymphoma cell proliferation, adhesion and drug resistance, and may lead to the generation of a novel therapeutic approach targeting this molecule.

Y-box-binding protein-1 (YB-1) promotes cell proliferation, adhesion and drug resistance in diffuse large B-cell lymphoma.

YB-1 is a multifunctional protein, which has been shown to correlate with resistance to treatment of various tumor types. This study investigated the expression and biologic function of YB-1 in diffuse large B-cell lymphoma (DLBCL). Immunohistochemical analysis showed that the expression statuses of YB-1 and pYB-1(S102) were reversely correlated with the clinical outcomes of DLBCL patients. In addition, we found that YB-1 could promote the proliferation of DLBCL cells by accelerating the G1/S transition. Ectopic expression of YB-1 could markedly increase the expression of cell cycle regulators cyclin D1 and cyclin E. Furthermore, we found that adhesion of DLBCL cells to fibronectin (FN) could increase YB-1 phosphorylation at Ser102 and pYB-1(S102) nuclear translocation. In addition, overexpression of YB-1 could increase the adhesion of DLBCL cells to FN. Intriguingly, we found that YB-1 overexpression could confer drug resistance through cell-adhesion dependent and independent mechanisms in DLBCL. Silencing of YB-1 could sensitize DLBCL cells to mitoxantrone and overcome cell adhesion-mediated drug resistance (CAM-DR) phenotype in an AKT-dependent manner.

Expression of vaccinia-related kinase 1 (VRK1) accelerates cell proliferation but overcomes cell adhesion mediated drug resistance (CAM-DR) in multiple myeloma.

OBJECTIVE: Vaccinia-related kinase 1 (VRK1) has been reported to participate in the development of a variety of tumors. However, the role of VRK1 in multiple myeloma (MM) has not been investigated. The present study was undertaken to determine the expression and biologic function of VRK1 in human MM. METHODS: First, we constructed a model of cell adhesion in MM, the mRNA and protein level of VRK1 in suspension and adhesion model was analyzed by RT-PCR and western blot. Then, flow cytometry assay and western blot were used to investigate the mechanism of VRK1 in the proliferation of MM cells. In vitro, following using shRNA interfering VRK1 expression, we performed adhesion assay and cell viability assay to determine the effect of VRK1 on adhesive rate and drug sensitivity. RESULTS: VRK1 was lowly expressed in adherent MM cells and highly expressed in suspended cells. In addition, VRK1 was positively correlated with the proliferation of MM cells by regulating the expression of cell cycle-related protein, such as cyclinD1, CDK2 and p27kip1. Furthermore, VRK1 could reverse cell adhesion mediated drug resistance (CAM-DR) by down-regulating the ability of cell adhesion. CONCLUSION AND DISCUSSION: Our data supports a role for VRK1 in MM cell proliferation, adhesion, and drug resistance, and it may pave the way for a novel therapeutic approach for CAM-DR in MM.

Cell adhesion induces overexpression of chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) and contributes to cell adhesion-mediated drug resistance (CAM-DR) in multiple myeloma cells.

Previous studies have shown that chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) exerts its anti-apoptotic function in many solid cancers. However, its role in human multiple myeloma (MM) has not been thoroughly elucidated. In this study, we investigate the role of CHD1L in MM. Preliminarily, up-regulation and down-regulation assay verified that CHD1L exerts its anti-apoptotic role through the apoptotic pathway involving caspase-9-caspase-3 apoptotic pathway in MM cells. In addition, we determined that CHD1L expression is increased when MM cells were adhered to fibronectin (FN) or bone marrow stromal cell line HS-5 cells and cell adhesion assay indicated that CHD1L siRNA reversed the high cell adhesion rate. Consistent with the reduced adhesion rate, the cells translated to a compromised cell adhesion-mediated drug resistance (CAM-DR) phenotype in MM. In summary, we will propose strategies for developing a CHD1L inhibitor for potential treatment of MM.

Cell adhesion downregulates the expression of Homer1b/c and contributes to drug resistance in multiple myeloma cells.

Previous studies have demonstrated that Homer1b/c plays an important pro-apoptotic role through classical mitochondrial apoptotic pathway. The present study was undertaken to determine the expression and functional significance of Homer1b/c in multiple myeloma (MM). We found that Homer1b/c was lowly expressed in MM cell apoptotic model induced by doxorubicin. The positive role of Homer1b/c in cell apoptosis was further confirmed by knocking down Homer1b/c. Further study confirmed that Homer1b/c was able to affect the CAM-DR via pro-apoptotic activity regulating the ability of cell adhesion. Collectively, these data indicate that Homer1b/c may represent a good candidate for pursuing clinical trial in MM.

Upregulation of nuclear transporter, Kpnß1, contributes to accelerated cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) in diffuse large B-cell lymphoma.

BACKGROUND: The Karyopherin proteins are involved in the shuttling of cargo proteins, and certain RNAs, across the nuclear pore complex into and out of the cell nucleus. Karyopherin ß1 (Kpnß1) is a member of the Karyopherin ß superfamily of nuclear transport proteins. In addition to the nuclear import function, Kpnß1 is associated with the occurrence of tumors. This study investigated the expression and biologic function of Kpnß1 in diffuse large B-cell lymphoma (DLBCL). METHODS: The prognostic value of Kpnß1 expression was evaluated using immunohistochemical staining. The role of Kpnß1 on cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) was also determined. RESULTS: We demonstrated that Kpnß1 mRNA and protein expression levels were significantly higher in DLBCL B-cells and DLBCL cell lines than in normal CD19 purified B-cells. Immunohistochemical analysis suggested that the expression of Kpnß1 was correlated with Ki-67 (P < 0.001). Kaplan-Meier curve showed that high expression of Kpnß1 was significantly associated with shorter overall survival. In addition, Kpnß1 was associated with the proliferation of DLBCL cells. Importantly, we found that Kpnß1 could interact with p65 and promote CAM-DR via accelerating NF-κB activation in DLBCL. CONCLUSIONS: Patients with tumors highly expressing Kpnß1 have poorer overall survivals. Kpnß1 interacts with p65 and enhances CAM-DR.

Elevated atmospheric CO2 affected photosynthetic products in wheat seedlings and biological activity in rhizosphere soil under cadmium stress.

The objective of this study was to investigate the effects of elevated CO2 (700 ± 23 µmol mol(-1)) on photosynthetic products in wheat seedlings and on organic compounds and biological activity in rhizosphere soil under cadmium (Cd) stress. Elevated CO2 was associated with decreased quantities of reducing sugars, starch, and soluble amino acids, and with increased quantities of soluble sugars, total sugars, and soluble proteins in wheat seedlings under Cd stress. The contents of total soluble sugars, total free amino acids, total soluble phenolic acids, and total organic acids in the rhizosphere soil under Cd stress were improved by elevated CO2. Compared to Cd stress alone, the activity of amylase, phenol oxidase, urease, L-asparaginase, ß-glucosidase, neutral phosphatase, and fluorescein diacetate increased under elevated CO2 in combination with Cd stress; only cellulase activity decreased. Bacterial abundance in rhizosphere soil was stimulated by elevated CO2 at low Cd concentrations (1.31-5.31 mg Cd kg(-1) dry soil). Actinomycetes, total microbial abundance, and fungi decreased under the combined conditions at 5.31-10.31 mg Cd kg(-1) dry soil. In conclusion, increased production of soluble sugars, total sugars, and proteins in wheat seedlings under elevated CO2 + Cd stress led to greater quantities of organic compounds in the rhizosphere soil relative to seedlings grown under Cd stress only. Elevated CO2 concentrations could moderate the effects of heavy metal pollution on enzyme activity and microorganism abundance in rhizosphere soils, thus improving soil fertility and the microecological rhizosphere environment of wheat under Cd stress.

Sam68 regulates cell proliferation and cell adhesion-mediated drug resistance (CAM-DR) via the AKT pathway in non-Hodgkin's lymphoma.

OBJECTIVES: Sam68 (Src-associated in mitosis 68 kDa), a substrate for tyrosine kinase c-Src during mitosis, is up-regulated in a variety of human cancers and acts oncogenically promoting tumour progression. This study has explored biological function and clinical significance of Sam68 in non-Hodgkin's lymphoma (NHL). MATERIALS AND METHODS: To examine Sam68 expression in NHL, clinically, eight diffuse large B-cell lymphomas and four reactive lymphoid hyperplasia fresh-frozen tissues were obtained for western blot and quantitative real-time PCR analyses. Using immunohistochemical staining, paraffin wax embedded sections from 164 cases of NHL patients were used to evaluate prognostic value of Sam68. Cell Counting Kit-8 (CCK-8) and soft agar colony assays were conducted to investigate the role of Sam68 in cell viability and cell proliferation respectively. Furthermore, effects of Sam68 on cell adhesion-mediated drug resistance (CAM-DR) was determined by CCK-8 assay and flow cytometric analysis. RESULTS: Expression status of Sam68 inversely correlated with clinical outcomes of patients with NHL, and it was also an independent prognostic factor for the outcomes. In addition, Sam68 was associated with proliferation of NHL cells. Knock-down of its gene inhibited cell proliferation and colony formation by delaying cell cycle progression. Furthermore, OCI-Ly8 and Jeko-1 cells adhering to FN and HS-5 expressed higher Sam68 protein, compared to their suspension counterparts. Sam68 promoted cell adhesion-mediated drug resistance (CAM-DR) via the AKT pathway. CONCLUSIONS: Increased Sam68 expression in NHL resulted in poor prognosis, and it promoted CAM-DR in NHL via AKT.

Pyruvate kinase isoform M2 (PKM2) participates in multiple myeloma cell proliferation, adhesion and chemoresistance.

Cell adhesion mediated drug resistance (CAM-DR) remains the major barrier in human multiple myeloma (MM) therapy. In the present study, we aimed at investigating the role of pyruvate kinase isoform M2 (PKM2) in MM CAM-DR. We determined that PKM2 expression was positively correlated with cell proliferation and knockdown of PKM2 contributed to the increased cell adhesion rate in MM. The enhancement in the adhesion of MM cells to fibronectin or the bone marrow stroma cell line HS-5 cells translated to an increased CAM-DR phenotype. Importantly, we showed that this CAM-DR phenotype was correlated with the phosphorylation of Akt and ERK in MM cells. Taken together, our data shed new light on the molecular mechanism of CAM-DR in MM, and targeting PKM2 may be a novel therapeutic approach for improving the effectiveness of chemotherapy in MM.