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Introduction Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF), is commonly used to prevent and/or treat neutropenia caused by tumor chemotherapy and radiotherapy with reduced clearance, increased plasma half-life, sustained biologic activity, and good safety. PEG-rhG-CSF anaphylaxis was rare. Case report A 55-year-old male Non-Hodgkin lymphoma patient appeared with chest tightness, increased heart rate, and decreased blood pressure after taking PEG-rhG-CSF used as a primary treatment for neutropenia caused by chemoradiotherapy. The patient’s anaphylaxis is likely due to PEG-rhG-CSF. Management and outcome 0.9% sodium chloride 250 mL and dexamethasone sodium phosphate injection 5 mg were carried out. After close observation, the symptoms were improved. Two months later, the patient was readministered with PEG-rhG-CSF and anaphylaxis reoccurred. After the last contact with PEG-rhG-CSF, the patient was prescribed rhG-CSF for many times and did not experience any adverse reactions. Discussion PEGylated drugs are not free of risk and immune-mediated adverse events are of concern. PEG is a substance capable of triggering an immune response. The mechanism of PEG involved IgE-mediated anaphylaxis and non-IgE-mediated anaphylaxis, and requires further research. PEGylated drugs are not free of risk and immune-mediated adverse events are of concern.

PurposeAE-848/33345007, is a novel small molecular compound that was independently synthesized by our laboratory. The aim of the current study was to investigate potential therapeutic effects of the small molecule compound AE-848 on human hepatoblastoma cells.MethodsHuman hepatoblastoma cell line HepG2 was cultured under different concentrations of AE-848. MTT assay was used to detect the inhibitory ability of AE-848 on the activity of this cell line, while flow cytometry was applied to quantify apoptosis. Western-blot technique was used to determine expression levels of signaling pathway-associated molecules. The antitumor in vivo activity of AE-848 against hepatoblastoma was evaluated using hepatoblastoma-bearing nude mice randomly divided into AE-848 (experimental) and saline (control) groups respectively. Changes in survival and tumor sizes were compared between these two groups.ResultsAE-848 significantly inhibited proliferation and induced apoptosis of HepG2 cells, and induced activation of PI3K/Akt/mTOR signaling pathways. More importantly, AE-848 administration significantly inhibited tumor growth and prolonged survival of hepatoblastoma-bearing mice.ConclusionAE-848 had a strong anti-hepatoblastoma activity both in vitro and in vivo, indicating the importance of developing AE-848 as a potential drug for hepatoblastoma treatment.

The plasma cell malignancy multiple myeloma (MM) has been improved significantly by new drugs application and autologous hemopoietic stem transplantation. However, MM remains incurable. A number of studies have revealed an anti-MM effect of Nature killer (NK) cells, but their clinical efficacy was rather limited. Glycogen synthase kinase (GSK)-3β has been shown to have an antitumor function. To evaluate potential roles of GSK-3β inhibitor (TWS119) in the regulation of NK cell cytotoxicity against MM, we analyzed killing effect of NK cells on MM cells. Our results showed that in the presence of TWS119, NK cell line (NK-92) and in vitro expanded primary NK cells exhibited a significantly higher degranulation activity, expression of activating receptors, cellular cytotoxicity and cytokine secretion when they were exposed to MM cells. Mechanistic studies indicated that TWS119 treatment markedly upregulated RAB27A expression, a key molecule for NK cell degranulation, and induced colocalization of β-catenin with NF-κB in the nucleus of NK cells. More importantly, adoptive transfer of NK-92 cells significantly prolonged survival time of myeloma-bearing mice. In summary, our current novel findings suggest that targeting on GSK-3β through activation of β-catenin/NF-κB pathway maybe an important approach to improve therapeutic efficacy of NK cells transfusion for MM.

The present study aimed to investigate whether co-administration of mesenchymal stromal cells (MSC) and linezolid (LZD) into a rabbit model of methicillin-resistant Staphylococcus aureus (MRSA)-infected pneumonia would bring a synergistic therapeutic effect. Human umbilical cord-derived MSCs (hUMSCs) were isolated and characterized. A rabbit model of pneumonia was constructed by delivering 1 × 1010 CFU MRSA via a bronchoscope into the basal segment of lower lobe of right lung. Through analyzing vital sign, pulmonary auscultation, SpO2, chest imaging, bronchoscopic manifestations, pathology, neutrophil percentage, and inflammatory factors, we verified that a rabbit model of MRSA-induced pneumonia was successfully constructed. Individual treatment with LZD (50 mg/kg for two times/day) resulted in improvement of body weight, chest imaging, bronchoscopic manifestations, histological parameters, and IL-10 concentration in plasma (P

Background Aneuploidy of chromosome 8 in circulating tumor cells (CTCs) has been reported correlates with therapeutic efficacy and prognosis in patients with advanced gastric cancer. However, it is not clear whether it is also appropriate for other cancer. Therefore, in this study, we evaluate the clinical application aneuploidy of CTCs for esophageal cancer. Methods Peripheral blood were collected for karyotyping analysis before and after first 4-cycles chemotherapy from seventy nine patients with newly diagnosed esophageal cancer. Karyotyping of chromosome 8 in CTCs detected by SET-iFISH (Subtraction Enrichment-Immunostaining fluorescence in situ hybridizatio) in those patients were grouped into two categories according to CTC number: triploid group and non-triploid group. Pearson Chi-Square were used to compare the association between different aneuploidy type and chemotherapeutic sensitivity and efficacy. Results Among the 16 patients with triploid of chromosome 8, 4 patients benefit, and of the 63 patients with non-triploid, 54 patients benefit. Chi-square test analysis found that clinical benefit of non-triploid patients was significantly higher than triploid patients, suggesting non-triploid patients were more sensitive to chemotherapy than triploid patients. After 4-cycles chemotherapy, it is found that chemotherapeutic efficacy was positively correlated with non-triploid proportion. These results suggest that non-triploid proportion could be used as a candidate maker for assessing chemotherapeutic efficacy. Conclusions Monitoring aneuploidy of chromosome 8 in CTCs before and after chemotherapy may help predict sensitivity and efficacy of chemotherapy in patients with esophageal cancer. Electronic supplementary material The online version of this article (10.1186/s12885-019-5850-7) contains supplementary material, which is available to authorized users.

Table S1. CTC karyotyping and chemotherapeutic efficacy of 79 esophageal cancer patients with first 2-cycles chemotherapy. (DOCX 27 kb)

Background: Leukemia is a cancer of the hematopoietic stem cells, which leads to an uncontrolled proliferation of leukocytes in blood. It is responsible for one of the most important cancer-associated deaths across the globe. Materials and Methods: In this study, we analyzed whether dieckol (DEK), a polyphenolic compound obtained from brown algae, can suppress cell proliferation via regulation of JAK/STAT3 signaling pathway in leukemia cell lines (Molt-4). Results: According to our results, DEK induced cytotoxicity, altered the cell morphology, caused nuclear damage, enhanced the formation of reactive oxygen species, decreased the production of mitochondrial membrane potential, reduced the levels of antioxidants (reduced glutathione, catalase, and superoxide dismutase), and augmented the level of thiobarbituric acid reactive substances in Molt-4 cell lines. Furthermore, STAT3 has been recognized as an important transcriptional mediator that controls cell proliferation. Thus, suppression of STAT3 transcription is a novel approach for the suppression of Molt-4 cell proliferation. In this study, DEK inhibited STAT3 translocation, thereby suppressing the increased expression of cyclin E1, PCNA, cyclin D1, and JAK1 in Molt-4 cell lines. Conclusion: In summary, DEK suppressed the cell proliferation of Molt-4 cells via inhibition of JAK/STAT3 signaling pathway.

OBJECTIVE: Hemophagocytic lymphohistiocytosis in adults is largely underdiagnosed. To improve the rate and accuracy of diagnosis in adults, the clinical and laboratory characteristics of hemophagocytic lymphohistiocytosis were analyzed in and compared between adults and children in a Chinese cohort. METHOD: Data from 50 hemophagocytic lymphohistiocytosis patients, including 34 adults and 16 children who fulfilled the 2004 hemophagocytic lymphohistiocytosis diagnostic criteria, were collected and analyzed. RESULTS: 1. Etiological factors: The proportion of Epstein-Barr virus infection was lower in adults compared with children, whereas fungal infection and natural killer/T cell lymphoma were more frequent in adults (P19 mmol/L and lactate dehydrogenase >500 U/L compared with adults (P

MicroRNAs (miRNAs) have attracted many attentions in lymphoma diagnostic research. The inconsistence of diagnostic performance in these existed literatures leading us to conduct this meta-analysis. In order to have a scientific and reliable study, all related articles were screened from Medline, Embase, CNKI and other databases. The sensitivity and specificity of each involved research were used to plot the summary receiver operator characteristic (SROC) curve and calculate the area under the curve (AUC). The QUADAS-2 tool was applied to estimate the quality of included studies. In addition, Deeks’ funnel plot asymmetry test was performed to estimate publication bias. Overall, 14 studies from 6 articles were included to evaluate the whole test performance. The overall pooled results were as follows: sensitivity was 0.91 (95% CI: 0.83-0.95), specificity was 0.84 (95% CI: 0.75-0.90), the AUC was 0.93 (95% CI: 0.91-0.95), positive likelihood ratio-PLR was 5.5 (95% CI: 3.5-8.8), negative likelihood ratio-NLR was 0.11 (95% CI: 0.06-0.21), and diagnostic odds ratio-DOR was 50 (95% CI: 19-128). In summary, results from meta-analysis showed that miRNAs analysis might significantly increase the diagnostic accuracy of lymphoma. Further massive prospective studies still needed to validate our conclusion before clinical application.

Type 2 diabetes mellitus (T2DM) is a serious threat to human health and remains incurable. Insulin deficiency seems to be attributed to the progressive failure of pancreatic islet β-cells and immune cells such as T cells mediated cytotoxicity may be involved in the loss of pancreatic islet β-cells in T2DM. Targeting on the immune system to maintain functional activity of pancreatic islet β-cells could be an attractive way to treat T2DM. Mesenchymal stem cells (MSCs) exert potent capacity of immunomodulation. MSCs have been successfully applied for the treatment of several types of autoimmune diseases. So, the aim of this study is to evaluate the safety and potential therapeutic effects of UMSC on T2DM.UMSCs were separated, expanded, and identified on the basis of the previous description. 18 patients of T2DM were recruited according to our experimental protocol. UMSC was intravenously transfused three times. All patients were followed up in the first, third, and sixth month. Age, gender, diabetes duration and medications as well as weight, height, and BMI were recorded. Fasting plasma glucose (FPG), postprandial blood glucose (PBG), HbA1c, C-peptide, and subsets of T cells were measured. All adverse reactions were carefully documented. Effective criteria were made and data was analyzed using SPSS 19.0 software.UMSCs were successful obtained. Baseline clinical characteristics between the efficacy and inefficacy groups were not statistically different (p0.05). FBG and PBG of the patients in efficacy group were significantly reduced (p0.05) after UMSC transfusion. Plasma C-peptide levels and regulatory T (Treg) cell number in the efficacy group were numerically higher after UMSC transfusion; however, the difference of both parameters did not reach significance (p0.05). During the treatment course only 4 out of 18 patients (22.2%) had slight transient fever. Up to 6 months after UMSC transfusion, all patients continued to have a feeling of well-being and were physically more active.UMSC transfusion is safe and well tolerated, effectively alleviates blood glucose, and increases the generation of C-peptide levels and Tregs in a subgroup of T2DM patients. This pilot study provides fundamental data for further study of UMSC transfusion on control of blood glucose as well as morbidity of T2DM in a larger cohort.

To detect the expression of cancerous inhibitor of phosphatase 2A (CIP2A) in chronic myelocytic leukemia (CML) and investigate the mechanism underlying CIP2A knockdown-mediated cell proliferation and apoptosis as well as the interaction of CIP2A with breakpoint cluster region-Abelson leukemia virus (BCR-ABL). CIP2A mRNA and protein expression in chronic myelocytic leukemia-chronic (CML-CP) patients and healthy controls were determined by RT-PCR and Western blot. In vivo, c-Myc expression, PP2A activity, cell proliferation, and apoptosis of CML cells were detected with CIP2A depletion. In addition, the relationship among CIP2A, BCR-ABL, and tyrosine phosphatase SHP-1 was explored by depleting/overexpressing CIP2A or inhibiting BCR-ABL. The level of CIP2A mRNA was higher in CML-CP patients than healthy controls (56/74, 75.7 % vs. 1/35, 2.9 %, P < 0.001), and CIP2A protein was overexpressed in corresponding specimens. CIP2A knockdown by siRNA reduced the level of c-Myc protein and clonogenic formation, inhibited the activity of PP2A, K562 cell proliferation, and promoted cell apoptosis. Suppressing BCR-ABL by imatinib mesylate (IM) significantly decreased CIP2A expression. CIP2A knockdown decreased BCR-ABL but increased SHP-1 expression, and CIP2A overexpression had the reverse effect. CIP2A is overexpressed in CML-CP patients, and its expression may promote CML pathogenesis. CIP2A and BCR-ABL can regulate each other in a positive feedback loop. CIP2A may be a useful therapeutic target in CML-CP, particularly in patients with IM resistance. However, further studies are needed to validate the interaction between CIP2A and BCR-ABL using other tyrosine kinase inhibitors than IM.

The aim of this study was to examine the hypothesis that a combination of proteasome inhibition by bortezomib and immune therapy with interleukin-12 (IL-12) can produce enhanced antitumor efficacy relative to the effects of either of these agents alone. A mouse xenograft model of myeloma was developed. The mice were randomly divided into saline control (NS), IL-12 (0.4 µg/animal; intraperitoneal), bortezomib (0.75 mg/kg; intravenous), and bortezomib+IL-12 groups. Effects of treatments on tumor growth were assessed by before and after treatment comparisons and group comparisons. The effects of various treatments on the number of peripheral blood lymphocytes and natural killer (NK) cells were assessed by complete blood count and flow cytometry analysis. The cell-killing function of NK cells in splenocytes was evaluated using the lactate dehydrogenase release assay. IL-12 treatment alone produced a mild decrease in tumor volume compared with control (P>0.05). Bortezomib alone resulted in substantial inhibition of tumor growth at varying time points, reaching ~65 and ~60% reduction in tumor volume after 15 and 21 days of therapy, respectively. At the same time points, the combination therapy produced ~75 and ~84% decreases in tumor growth, respectively, which were significantly greater than the reduction produced by bortezomib monotherapy. Tumors resumed growth upon termination of bortezomib treatment at 2 weeks, although the tumor volume was still significantly smaller than that in the time-matched NS and IL-12 animals. This rebound of tumor growth was completely prevented with the combination therapy, and tumor volume continued to decrease throughout the time course. The percentage and total number of NK cells were significantly decreased after bortezomib monotherapy and combination therapy; however, they remained unaltered after IL-12 treatment compared with no treatment. Further, combination therapy significantly restored the bortezomib-induced functional impairment of the cell-killing capability of NK cells, relative to bortezomib alone. We conclude that the bortezomib-IL-12 combination therapy offers superior antitumor efficacy over monotherapy with either bortezomib or IL-12 in a mouse model of myeloma. Restoration of bortezomib-induced functional impairment of NK cells by IL-12 may be a mechanism for the synergetic effects of the two agents. Therefore, a combination of the two agents may represent a more rational therapeutic approach for myeloma.