Quantitative assessment of changes in skeletal muscle injury by computer-aided analysis based on two-dimensional ultrasonography combined with contrast-enhanced ultrasonography and estimated by a modified semi-quantitative scoring system: An experimental study in a contusion model.

The aim of this study was to investigate the potential application of computer-aided analysis in the quantitative assessment of changes in skeletal muscle injury in the rabbit contusion model. Forty healthy rabbits were randomly divided into control (n = 5) and contusion (n = 35) groups. Rabbits in the contusion group were used to construct a muscle contusion model induced by a hammer hitting the right gastrocnemius, while the muscles of rabbits in the control group were non-injured. Two-dimensional ultrasound (2D US) and contrast-enhanced ultrasonography (CEUS) were performed on the rabbits that had received skeletal muscle contusion injury at 1 h, and 1, 3, 7, 14, 21 and 28 days after injury. Afterwards, a multiscale blob feature (MBF) method was used to extract the textural features from the 2D US, and the muscle injuries were quantitatively evaluated. The eight textural parameters of skeletal muscle analysed by MBF at 1 h, and 1, 3 and 7 days post-injury were found to be significantly higher in the contusion group than in the control group (p < .05). On Day 14, the textural parameters (e.g., greyscale mean [Mean], greyscale standard deviation [SDev], number of blobs, average size of blobs, homogeneity of distribution, periodicity of distribution [POD] and irregularity) were also evidently higher in the contusion group than in the control group (p < .05). On Day 28, Mean, SDev and POD in the contusion group were markedly higher (p < .05). After that, the microcirculation in the injured areas increased from Day 7 to Day 21 after injury, but decreased on Day 28 after injury. Thus the quantitative assessment of changes in skeletal muscle injury (SMI) using computer-aided analysis allowed us to describe the geometric features of injured muscle fibres and the microperfusion changes estimated by the modified semi-quantitative scoring system. This provides a scientific basis for the development of a novel approach for the evaluation of SMI and rehabilitation process.

Dynamic monitoring of cardiac foreign body by perioperative echocardiography: A case study.

Cardiac foreign bodies, especially those with sharp tips, may lead to unpredictable complications, such as penetrating cardiac injuries. Yet there have not been many reports of penetrating cardiac injuries caused by a needle that migrates from the neck to the heart. We herein present a review of such a case, focusing on the dynamic monitoring by perioperative echocardiography. The needle was represented on the monitor as a linear artifact that had penetrated through the ventricular wall and caused increasing pericardial effusion. Fortunately, the needle was successfully removed before it completely entered the right ventricular cavity. In this case, perioperative echocardiography played a significant role in clinical emergency decision making.

Is it safe to withdraw steroids within seven days of renal transplantation?

BACKGROUND: The safety of very early steroid withdrawal (VESW) in renal transplant recipients remains unclear. METHODS: Literature searches for all randomized controlled trials comparing VESW with steroid maintenance regimens were performed using MEDLINE, EMBASE, and the Cochrane Library. Quality assessment was performed in each trial. Meta-analyses were performed to demonstrate the pooled effects of relative risk (RR) and weighted mean difference with 95% confidence intervals (CI). RESULTS: A total of 3520 participants from 15 RCTs were included. VESW regimen increased the incidence of acute rejection (AR) over controls (RR = 1.46, CI = 1.20-1.79, p = 0.04). Subsequent analysis demonstrated that such difference lost significance in patients receiving tacrolimus (p = 0.16), but remained significant in patients with cyclosporin (p < 0.00001). The increased AR episodes were predominantly mild. VESW was associated with an increased incidence of delayed graft function (DGF) when steroids were withdrawn within three d post-transplantation. Cardiovascular risk factors, including incidence of new onset diabetes and total cholesterol, were significantly reduced under VESW regimen. CONCLUSIONS: It is safe and practical to withdraw steroids very early after renal transplantation. However, a three- to seven-d course of steroids may decrease the risk for DGF relative to steroid withdrawal in <3 d. Antibody induction is effective in preventing early AR.

Independent prognostic value of left ventricular mass index in patients with light-chain amyloidosis.

BACKGROUND: Echocardiographic-determined left ventricular mass index (LVMI) provides quantitative information on left-ventricular structure. However, its prognostic value on light-chain (AL) amyloidosis has not been clearly defined. METHODS: We included 99 patients with newly diagnosed AL amyloidosis between July 2013 and March 2022. Clinical features and echocardiographic parameters were collected. RESULTS: LVMI ≥113.4 g/m2 was predictive for overall survival (OS) and progression-free survival (PFS) with respective hazard ratios (HRs) of 2.87 (95% CI: 1.04-7.79) and 2.91 (95% CI: 1.25-6.68). Patients in the LVMI-high group had higher NT-proBNP, cTnT, and FLC-diff levels. They were more likely to be cardiac involved and have increased mean left ventricular wall thickness, decreased left ventricular ejection fraction, and higher proportion of patients with pericardial effusion. In subgroup analysis, LVMI-high group was associated with a reduced OS [HR: 4.74 (95% CI: 1.26-17.77)] and PFS [HR: 7.16 (95% CI: 2.10-24.40)] in patients with cardiac amyloidosis (CA). Besides, LVMI-high was associated with a reduced OS [HR: 3.58 (95% CI: 1.17-11.02)] and PFS [HR: 4.79 (95% CI: 1.77-12.94), p = 0.00] among patients staged of II or III (Mayo 2004), as well as reduced OS [HR: 22.65 (95% CI: 1.66-299.31)] and PFS [HR: 18.73 (95% CI: 2.36-148.35)] among patients staged of III or IV (Mayo 2012). CONCLUSIONS: LVMI is a reliable prognostic indicator of survival. A cut-off of LVMI (113.4 g/m2) was prognostic for OS and PFS. Importantly, LVMI was able to identify a subset of patients with poorer prognosis in the context of CA or in the late stages according to the biomarker staging systems.

Percutaneous cholecystostomy versus emergency cholecystectomy for the treatment of acute calculous cholecystitis in high-risk surgical patients: a meta-analysis and systematic review.

The present meta-analysis was performed to compare the efficacy and safety of percutaneous cholecystostomy (PC) versus emergency cholecystectomy (EC) for the treatment of acute calculous cholecystitis (ACC) in high-risk surgical patients. Literature searches for eligible studies were performed using MEDLINE, EMBASE and the Cochrane Library. Quality assessment was conducted in each study. Meta-analyses were performed to demonstrate the pooled effects of relative risk (RR) with 95% confidence intervals (CI). A total of 8960 patients from 6 studies were finally included. PC resulted in increased risks of mortality (RR = 2.87; CI = 1.33-6.18; p = 0.007) and readmission rate (RR = 4.70; CI = 3.30-6.70; p < 0.00001) as compared with EC. No significant difference was detected between PC and EC in terms of morbidity, severe complication rate or hospitalization length. Moreover, PC was associated with significantly higher risks of mortality (RR = 7.47; CI = 1.88-29.72; p = 0.004), morbidity (RR = 3.71; 95% CI = 1.78-7.75; p = 0.0005), readmission rate (RR = 7.91; CI = 3.80-16.49; p < 0.00001), and hospitalization length (WMD = 6.92; CI = 5.89-7.95; p < 0.00001) when directly compared with laparoscopic cholecystectomy (LC). Therefore, EC is superior to PC for the treatment of ACC in high-risk surgical patients, and LC is the preferred surgical strategy.

Establishment of a nomogram for predicting lymph node metastasis in patients with early gastric cancer after endoscopic submucosal dissection.

Background: Endoscopic submucosal dissection (ESD) has been accepted as the standard treatment for the appropriate indication of early gastric cancer (EGC). Determining the risk of lymph node metastasis (LNM) is critical for the following treatment selection after ESD. This study aimed to develop a predictive model to quantify the probability of LNM in EGC to help minimize the invasive procedures. Methods: A total of 952 patients with EGC who underwent radical gastrectomy were retrospectively reviewed. LASSO regression was used to help screen the potential risk factors. Multivariate logistic regression was used to establish a predictive nomogram, which was subjected to discrimination and calibration evaluation, bootstrapping internal validation, and decision curve analysis. Results: Results of multivariate analyses revealed that gender, fecal occult blood test, CEA, CA19-9, histologic differentiation grade, lymphovascular invasion, depth of infiltration, and Ki67 labeling index were independent prognostic factors for LNM. The nomogram had good discriminatory performance, with a concordance index of 0.816 (95% CI 0.781-0.853). The validation dataset yielded a corrected concordance index of 0.805 (95% CI 0.770-0.842). High agreements between ideal curves and calibration curves were observed. Conclusions: The nomogram is clinically useful for predicting LNM after ESD in EGC, which is beneficial to identifying patients who are at low risk for LNM and would benefit from avoiding an unnecessary gastrectomy.

Updated Evaluation of the Diagnostic Performance of Double Contrast-Enhanced Ultrasonography in the Preoperative T Staging of Gastric Cancer: A Meta-Analysis and Systematic Review.

Objective: This study aimed to systematically evaluate the diagnostic performance of double contrast-enhanced ultrasonography (DCEUS) in the preoperative T staging of gastric cancer (GC). Methods: Literature searches for eligible studies were performed using MEDLINE, EMBASE, and Cochrane Library. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve of DCEUS in the diagnosis of each T stage tumor were calculated. Meta-analyses were performed to obtain the pooled effects of risk ratio (RR) with 95% confidence interval (CI) in the comparison of DCEUS with CT/endoscopic ultrasound (EUS). Results: A total of 8 studies including 1,232 patients were identified for inclusion in this meta-analysis. The pooled sensitivity and specificity were 0.78 (95% CI = 0.64-0.88) and 0.98 (95% CI = 0.96-0.99) for T1, 0.81 (95% CI = 0.76-0.86) and 0.96 (95% CI = 0.91-0.98) for T2, 0.88 (95% CI = 0.84-0.91) and 0.85 (95% CI = 0.79-0.90) for T3, and 0.81 (95% CI = 0.69-0.89) and 0.96 (95% CI = 0.93-0.97) for T4. Moreover, DCEUS demonstrated significant superiority to CT in diagnosing T1 (RR = 1.57, 95% CI = 1.20-2.05, p = 0.001) and T2 (RR = 1.41, 95% CI = 1.16-1.71, p = 0.001) and to EUS in diagnosing T3 (RR = 1.24, 95% CI = 1.08-1.42, p = 0.003) and T4 (RR = 1.40, 95% CI = 1.09-1.79, p = 0.008). However, it showed a lower diagnostic accuracy than EUS in T1 tumors (RR = 0.77, 95% CI = 0.62-0.94, p = 0.013). Conclusions: DCEUS is a feasible complementary diagnostic tool for clinical T staging of GC. However, it is still far from a definitive conclusion for DCEUS to be proposed for use in routine clinical practice.

Folate Decorated Multifunctional Biodegradable Nanoparticles for Gastric Carcinoma Active Targeting Theranostics.

Introduction: Gastric cancer remains a major clinical issue and little progress has been made in the treatment of gastric cancer patients during recent decades. Nanoparticles provide a versatile platform for the diagnosis and treatment of gastric cancer. Methods: We prepared 7-ethyl-10-hydroxycamptothecin (SN-38) 125I-radiolabelled biodegradable nanoparticles with folate surface modification (125I-SN-38-FA-NPs) as a novel nanoplatform for targeted gastric carcinoma theranostics. We characterized this system in terms of particle size, morphology, radiostability, and release properties and examined the in vitro cytotoxicity and cellular uptake properties of 125I-SN-38-FA-NPs in MNK 7 and NCI-N7 cells. The pharmacokinetics and biodistribution of 125I-SN-38-FA-NPs were imaged by single photon emission computer tomography (SPECT). An MNK7 tumor-bearing model were established and the in vivo antitumor activity of 125I-SN-38-FA-NPs was evaluated. Results: SN-38 was readily radiolabeled with 125I and exhibited high radiostability. Poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) were formed by solvent exchange, and displayed spherical morphology of 100 nm in diameter as characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). A 2.5-fold greater uptake of 125I-radiolabelled SN-38-loaded folate-decorated PLGA nanoparticles (125I-SN-38-FA-NPs) than 125I-radiolabelled SN-38-loaded PLGA nanoparticles (125I-SN-38-NPs) were record in MKN7 tumor cells. NPs and folate-decorated PLGA nanoparticles (FA-NPs) also had good biocompatibility in methyl thiazolyl tetrazolium (MTT) assays. Pharmacokinetic, biodistribution and SPECT imaging studies showed that 125I-SN-38-FA-NPs had prolonged circulation, were distributed in the reticuloendothelial system, and had high uptake in tumors with a higher tumor accumulation of 125I-SN-38-FA-NPs than 125I-SN-38-NPs recorded at 24 h postinjection. In vivo SN-38-FA-NPs significantly inhibited tumor growth without causing obvious side effects. Conclusion: Folate receptor alpha (FOLR1) targeted drug-loaded nanoparticles enable SPECT imaging and chemotherapy, and provide a novel nanoplatform for gastric carcinoma active targeting theranostics.

Neoadjuvant Intraperitoneal and Systemic Chemotherapy Versus Neoadjuvant Systemic Chemotherapy With Docetaxel, Oxaliplatin, and S-1 for Gastric Cancer With Peritoneal Metastasis: A Propensity Score Matched Analysis.

BACKGROUND: The optimal treatment for gastric cancer with peritoneal metastasis (GCPM) remains debatable. This study aimed to compare the efficacy and safety of neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) versus neoadjuvant systemic chemotherapy (NSC) for GCPM. METHODS: Patients of GCPM received neoadjuvant chemotherapy with docetaxel, oxaliplatin and S-1 between January 2011 and June 2019 were retrospectively evaluated. Propensity score matched (PSM) analysis was carried out to reduce the selection bias. Multivariate Cox regression model was applied to screen the prognostic factors. RESULTS: After PSM processing, 71 patients in each group were matched among the 186 GCPM patients included. NIPS yielded a better ascites and cytology response to chemotherapy, higher conversion resection rate and R0 resection rate than NSC. The overall survival (OS) rate in NIPS group was better than that in NSC group. Multivariate analysis revealed that the P stage, ascites response, conversion surgery rate and R0 resection rate were independent prognostic factors. Subgroup analysis indicated that NIPS showed a survival benefit over NSC only in patients with cT3-4a, P1-2, whose cytology turned negative, and who received conversion surgery; while not in patients with cT4b, P0 or P3, whose cytology did not turn negative, or who did not receive conversion surgery. CONCLUSIONS: NIPS is a safe and feasible treatment for GCPM, which showed more benefit than NSC.

Comparison of Docetaxel + Oxaliplatin + S-1 vs Oxalipatin + S-1 as Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer: A Propensity Score Matched Analysis.

BACKGROUND: What is the optimal neoadjuvant chemotherapy (NAC) regimen for locally advanced gastric cancer (LAGC) remains debatable. The objective of this study was to compare the efficacy of docetaxel+oxaliplatin+S-1 (DOS) vs oxaliplatin+S-1 (SOX) as NAC for LAGC. METHODS: Data of 248 LAGC patients who received either DOS or SOX as NAC in our hospital between January 2010 and January 2018 were reviewed retrospectively. Propensity score matched (PSM) analysis was applied to minimize the selection bias in both groups. Prognostic factors were screened by univariate and multivariate Cox regression analyses. RESULTS: Of the 248 LAGC patients included, 180 patients were subjected to the PSM analysis. Patients in DOS group showed a better tumor response to NAC, higher radical resection rate and R0 resection rate than those in SOX group. The overall survival (OS) rate in DOS group was better than that in SOX group, although the overall incidence of Grade 3/4 NAC-related toxicity in DOS group was higher, as represented by leukopenia and neutropenia. Multivariate analysis revealed that the NAC regimen, cTNM stage and the R0 resection rate were independent prognostic factors. In addition, patients with TLND less than 16 population showed a worse OS rate. Subgroup analysis indicated that patients benefited from the addition of docetaxel regardless of the clinical T stage, but those with high clinical N stages (N2-3) did not. CONCLUSION: DOS is a safe and feasible NAC regimen for LAGC, which is worth popularizing in clinical practice.

Unfolded protein response inducers tunicamycin and dithiothreitol promote myeloma cell differentiation mediated by XBP-1.

The unfolded protein response (UPR) is an essential pathway for both normal and malignant plasma cells to maintain endoplasmic reticulum (ER) homeostasis in response to the large amount of immunoglobulin (Ig) output. The inositol-requiring enzyme 1-X-box binding protein-1 (IRE1-XBP-1) arm of the UPR pathway has been shown to play crucial roles not only in relieving the ER stress by up-regulating a series of genes favoring ER-associated protein degradation and protein folding, but in mediating terminal plasmacytic differentiation and maturation. Myeloma cells comprise various subsets arrested in diverse differentiated phases, and the immaturity of myeloma cells has been taken as a marker for poor prognosis, suggesting that differentiation induction would be a promising therapeutic strategy for myeloma. Herein, we used low-dose pharmacological UPR inducers such as tunicamycin (TM) and dithiothreitol (DTT) to efficiently activate the IRE1-XBP-1 pathway in myeloma cells characterized by transcriptional expression increase in spliced XBP-1 and molecular chaperons, accompanied by significant differentiation and maturation of these myeloma cells, without concomitant cytotoxicity. These differentiated myeloma cells exhibited a more mature appearance with well-developed cytoplasm and a reduced nucleocytoplasmic ratio, and a further differentiated phenotype with markedly increased expression of CD49e together with significantly elevated cellular secretion of Ig light chain as shown by flow cytometry and ELISA, in contrast to the control myeloma cells without exposed to TM or DTT. Moreover, siRNA knockdown of XBP-1 disrupted TM- or DTT-induced myeloma cell differentiation and maturation. Our study, for the first time, validated that the modest activation of the UPR pathway enables myeloma cells to further differentiate, and identified that XBP-1 plays an indispensable role in UPR-mediated myeloma cell differentiation and maturation. Thus, we provided the rationale and feasibility for the exploration of the novel therapeutic strategy of differentiation induction for plasmacytic malignancies.

ß-catenin SUMOylation is involved in the dysregulated proliferation of myeloma cells.

Over-activation of SUMOylation is correlated with poor prognosis in multiple myeloma (MM), with the mechanism unclear. Wnt signaling is one of the aberrantly regulated pathways related to cancer tumorigenesis and progression. Whether SUMOylation is involved in regulating the activity of Wnt/ß-catenin pathway, however, has not been reported in MM. Here we found that the TOPflash reporter activity and the expression of Wnt/ß-catenin target genes can be down-regulated after interference with SUMOylation through SUMO-1 small interfering RNA (siRNA). SUMOylation inhibition down-regulated ß-catenin at protein level via promotion of ubiquitin-proteasomal mediated degradation. Furthermore, over-expression of ß-catenin rescued Wnt/ß-catenin pathway activity and partially prevented increased apoptosis and growth inhibition induced by SUMOylation inhibition, indicating that ß-catenin was responsible for the observed effect on Wnt/ß-catenin pathway. To gain a clearer view, we exploited the inter-protein interactions of ß-catenin and SUMO-1 in myeloma cell lines. Immunoprecipitation and immunofluorescence assay proved that ß-catenin is subjected to SUMOylation in vivo, which may, at least partially explain the impact of SUMOylation inhibition on ß-catenin. The association of SUMO-1 and ß-catenin was confirmed in myeloma patient samples. Taken together, our data proved that SUMOylation inhibition down-regulates Wnt/ß-catenin pathway by promoting the ubiquitin-proteasomal mediated degradation of ß-catenin. SUMOylation of ß-catenin is part of the mechanisms involved in the dysregulated proliferation of myeloma cells.

Disruption of the unfolded protein response (UPR) by lead compound selectively suppresses cancer cell growth.

Identifying chemotherapy candidates with high selectivity against cancer cells is a major challenge in cancer treatment. Tumor microenvironments cause chronic endoplasmic reticulum (ER) stress and activate the unfolded protein response (UPR) as an adaptive response. Here, one novel small-molecule compound, 17#, was discovered as a potent pan-UPR inhibitor. It exhibited good selection for growth inhibition when cancer cells were cultured in 2-deoxy-D-glucose (2DG), mimicking an in vitro glucose-deprived status. Additionally, 17# alone could mildly suppress the growth of HeLa tumor xenografts, and a synergistic anti-cancer effect was observed when 17# was combined with 2DG. A mechanistic study showed that 17#-induced selective anti-cancer effects were highly dependent on UPR inhibition, and overexpressing GRP78 or XBP1s reversed the 17#-induced growth inhibition and cell cycle arrest, partially by delaying the downregulation of the cell cycle regulator cyclin B1. Furthermore, 17# improved the sensitivity of anti-cancer drugs such as doxorubicin or etoposide. Our study presents evidence that disrupting the UPR has selective therapeutic potential and may enhance drug sensitivity.

Is concomitant radiotherapy necessary with gemcitabine-based chemotherapy in pancreatic cancer?

AIM: To evaluate the efficacy and safety of gemcitabine (GEM) plus radiotherapy compared with GEM alone for pancreatic cancer (PC). METHODS: A systematic search for eligible studies comparing gemcitabine plus radiotherapy with gemcitabine alone for PC was performed using MEDLINE, EMBASE, and the Cochrane Library. A quality assessment was performed in each study. Meta-analyses were performed to study the pooled effects of relative risk with 95% confidence interval (CI). RESULTS: A total of 336 participants from four original studies were included. Gemcitabine plus radiotherapy resulted in comparable overall survival (HR = 0.84, 95%CI: 0.53-1.34, P = 0.48) and progress free survival (HR = 0.99, 95%CI: 0.97-1.01, P = 0.36) to gemcitabine alone. Moreover, concomitant radiotherapy was associated with a significantly higher incidence of severe (grade 3 or greater) toxicities, mainly anemia, leukocytopenia, thrombocytopenia, anorexia, nausea/vomiting, and asthenia/fatigue. CONCLUSION: Radiotherapy is not beneficial with gemcitabine-based chemotherapy for PC. Further exploration for better radiotherapy approaches and therapeutic regimens for the treatment of PC is warranted.

Bortezomib-thalidomide-based regimens improved clinical outcomes without increasing toxicity as induction treatment for untreated multiple myeloma: a meta-analysis of phase III randomized controlled trials.

Novel agents thalidomide and bortezomib have significantly improved myeloma treatment. However, it remains unclear whether patients will benefit more from the combination therapy of these two agents. Our meta-analysis aims to compare the efficiency, and more importantly, the safety of bortezomib-thalidomide-based (VT-based) versus bortezomib-based or thalidomide-based (V-based/T-based) regimens as induction therapy in patients with previously untreated myeloma. Overall, five phase III RCTs including 1765 patients were identified. Compared with V-based or T-based regimens, VT-based regimens significantly improved CR (OR=2.22, 95% CI [1.44, 3.43]), ORR (OR=2.19, 95% CI [1.51, 3.19]) as well as PFS (HR=0.69, 95% CI [0.54, 0.88]), but not OS (HR=1.04, 95% CI [0.91, 1.19]). Notably, most expected side effects of bortezomib or thalidomide were comparable in both groups, including hematologic (anemia, neutropenia, thrombocytopenia), nonhematologic (peripheral neuropathy, deep venous thrombosis, infections, gastrointestinal events) side effects and discontinuation during or after induction therapy. These results suggest that combination of thalidomide and bortezomib might be a better first-line choice for patients with untreated myeloma.

Transfection of chimeric anti-CD138 gene enhances natural killer cell activation and killing of multiple myeloma cells.

Reprogramming of NK cells with a chimeric antigen receptor (CAR) proved an effective strategy to increase NK cell reactivity and recognition specificity toward tumor cells. To enhance the cytotoxicity of NK cells against CD138-positive multiple myeloma (MM) cells, we generated genetically modified NK-92MI cells carrying a CAR that consists of an anti-CD138 single-chain variable fragment (scFv) fused to the CD3ζ chain as a signaling moiety. The genetic modification through a lentiviral vector did not affect the intrinsic cytolytic activity of NK-92MI toward human erythroleukemic cell line K562 cells or CD138-negative targets. However, these retargeted NK-92MI (NK-92MI-scFv) displayed markedly enhanced cytotoxicity against CD138-positive human MM cell lines (RPMI8226, U266 and NCI-H929) and primary MM cells at various effector-to-target ratios (E:T) as compared to the empty vector-transfected NK-92MI (NK-92MI-mock). In line with the enhanced cytotoxicity of NK-92MI-scFv, significant elevations in the secretion of granzyme B, interferon-γ and proportion of CD107a expression were also found in NK-92MI-scFv in response to CD138-positive targets compared with NK-92MI-mock. Most importantly, the enhancement in the cytotoxicity of NK-92MI-scFv did not attenuate with 10Gy-irradiation that sufficiently blocked cell proliferation. Moreover, the irradiated NK-92MI-scFv exerted definitely intensified anti-tumor activity toward CD138-positive MM cells than NK-92MI-mock in the xenograft NOD-SCID mouse model. This study provides the rationale and feasibility for adoptive immunotherapy with CD138-specific CAR-modified NK cells in CD138-positive plasmacytic malignancies, which potentially further improves remission quality and prolongs the remission duration of patients with MM after upfront chemotherapy.

[Sumoylation and its role in hematological disease].

Small ubiquitin-related modifier (SUMO) can be covalently attached to target proteins and thereby plays a crucial role in regulating the normal functions of cells, such as protein-protein interaction, subcellular localization, DNA repair, cell cycle and transcription factor regulation. Several lines have implicated that sumoylation is important in disease occurrence and development. This brief review will focus on some recent findings about the roles of sumoylation in the etiology and treatment of hematological malignancies.

Alemtuzumab induction in renal transplantation: a meta-analysis and systemic review.

OBJECTIVE: To compare the efficacy and safety of alemtuzumab versus traditional antibodies for induction therapy in renal transplantation. METHODS: Literature searches for all randomized controlled trials comparing alemtuzumab with traditional antibodies for post renal transplant induction therapy were performed using MEDLINE, EMBASE and the Cochrane Library. Quality assessment was performed in each trial. Meta-analyses were performed to demonstrate the pooled effects of relative risk (RR) with 95% confidence intervals (CI). RESULTS: A total of 808 participants from six randomized controlled trials (RCTs) were included. Alemtuzumab was associated with lower incidence of biopsy-proven acute rejection over traditional antibodies (RR 0.63, CI 0.45-0.87, p=0.005). This difference remained when only studies comparing alemtuzumab with rabbit antithymocyte globulin were included (RR 0.32, CI 0.11-0.91, p=0.03), but lost significance when only patients at high-risk were included (RR 0.86, CI 0.48-1.55, p=0.62). No significant differences were detected between alemtuzumab and traditional antibodies in terms of delayed graft function, patient death, graft loss, and safety profile. CONCLUSIONS: Alemtuzumab induction is superior to traditional antibodies in preventing AR in renal transplantation, but this benefit may not extend to recipients at high immunologic risk. The lower rejection rates do not translate into a uniform increase in graft or patient survival.