Global, regional and national burden of non-Hodgkin lymphoma from 1990 to 2017: estimates from global burden of disease study in 2017.

BACKGROUD: Non-Hodgkin lymphoma (NHL) is a common B/NK/T cell lymphoma. We collected detailed data about the incidence and mortality of NHL from Global Burden of Disease (GBD) Study in 2017 and extensively assessed the disease burden of NHL at the global level and also analysed its current trends according to sex, age, socio-demographic index (SDI), country and region. METHODS: By obtaining relevant data from Global Burden of Disease Study in 2017, estimated annual percentage changes (EAPCs) of age-standardized rate (ASR) were calculated to assess the current trends of the rate of incidence and mortality. RESULTS: Globally, ASR of incidence in NHL was increased while ASR of mortality and its annual percentage change was relatively stable. EAPCs in the incidence of NHL decreased in the low SDI regions but increased in the high SDI regions. The ratio of male to female mortalities was the highest in the 50-69-year-old age group, especially in the middle and middle-high SDI regions. CONCLUSION: The incidence of NHL was increased globally, whereas the deaths and its annual percentage change were relatively stable from 1990 to 2017.Key messagesAge-standardized rate (ASR) of incidence in NHL was increased globally from 1990 to 2017.ASR of mortality and its annual percentage change in NHL were relatively stable globally from 1990 to 2017.Estimated annual percentage changes (EAPCs) in the incidence of NHL decreased in the low socio-demographic index (SDI) regions but increased in the high SDI regions.

Delisheng induces antiproliferation and apoptosis effects in Hep3B cells via modulation of angiogenic proteins.

Delisheng is a widely used antineoplastic agent in China. Although previous studies revealed that Delisheng exhibits numerous pharmacological effects including the inhibition of cancer cell differentiation and enhancement of immune function with the lowest toxicity, the precise anticancer mechanisms of Delisheng in human hepatocellular carcinoma (HCC) cells remains largely unknown. The present study investigated the potential mechanisms underlying the anticancer properties of Delisheng on Hep3B cells. Delisheng demonstrated a strong anti-proliferation effect on Hep3B cells compared with normal liver HL-7702 cells, as detected by MTT assays. In addition, Delisheng arrested the cells in G/G1 phase. Furthermore, it exhibited a pro-apoptotic effect on Hep3B cells, as detected by flow cytometry. When exposed to Delisheng, Hep3B cells demonstrated decreased vascular endothelial growth factor (VEGF) and osteopontin (OPN) and increased endostatin (ES) protein expressions, as detected using immunocytochemistry staining and western blotting. These data suggest that Delisheng induces antiproliferation and apoptosis of Hep3B cells via modulation of VEGF, OPN and ES protein expression. It is hypothesized that Delisheng may be used as a novel anticancer therapeutic in HCC.

The clinical use of the platelet/lymphocyte ratio and lymphocyte/monocyte ratio as prognostic predictors in colorectal cancer: a meta-analysis.

BACKGROUND: Conflicting evidence exists regarding the effects of platelet/lymphocyte ratio (PLR) and lymphocyte/monocyte ratio(LMR) on the prognosis of colorectal cancer (CRC) patients. This study aimed to evaluate the roles of the PLR and LMR in predicting the prognosis of CRC patients via meta-analysis. METHODS: Eligible studies were retrieved from the PubMed, Embase,andChina National Knowledge Infrastructure (CNKI) databases, supplemented by a manual search of references from retrieved articles. Pooled hazard ratios (HR) with 95% confidence intervals (95% CI) were calculated using the generic inverse variance and random-effect model to evaluate the association of PLR and LMR with prognostic variables in CRC, including overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS). RESULTS: Thirty-three studies containing 15,404 patients met criteria for inclusion. Pooled analysis suggested that elevated PLR was associated with poorer OS (pooled HR = 1.57, 95% CI: 1.41 - 1.75, p< 0.00001, I2=26%) and DFS (pooled HR = 1.58, 95% CI: 1.31 - 1.92, p< 0.00001, I2=66%). Conversely, high LMR correlated with more favorable OS (pooled HR = 0.59, 95% CI: 0.50 - 0.68, p< 0.00001, I2=44%), CSS (pooled HR = 0.54, 95% CI: 0.40 - 0.72, p< 0.00001, I2=11%) and DFS (pooled HR = 0.82, 95% CI: 0.71- 0.94,p=0.005, I2=29%). CONCLUSIONS: Elevated PLR was associated with poor prognosis, while high LMR correlated with more favorable outcomes in CRC patients. Pretreatment PLR and LMR could serve as prognostic predictors in CRC patients.

The blockage of Notch signalling promoted the generation of polymorphonuclear myeloid-derived suppressor cells with lower immunosuppression.

Myeloid-derived suppressor cells (MDSCs) mostly consisting of polymorphonuclear (PMN)-MDSCs and mononuclear MDSCs have been considered to play critical roles in immunosuppression, angiogenesis, invasion and metastases of various tumours. However, it is still unclear the regulated mechanisms underlying the generation and immunosuppression of two major MDSC subsets. Here, we report Notch signalling was inhibited significantly in tumour-bearing mouse MDSCs, in which PMN-MDSCs were the major population. MDSCs without recombination signal binding protein-Jк (RBP-J), the critical transcription factor mediating signalling from all four mammalian Notch receptors, reduced their ability of inhibiting the proliferation and activation of allogenic T cells. RBP-J-deficient MDSCs could not down-regulate the expression of co-stimulation molecules on dendritic cells (DCs). The antigen presentation capacity of DCs co-cultured with RBP-J-deficient MDSCs was not impaired in contrast to controls. Moreover, we show the blockage of Notch signalling could improve the generation of PMN-MDSCs but inhibit the production of mononuclear MDSCs both in vitro and in vivo. Stat3 pathway was suppressed in MDSCs blocked Notch signalling and Stat3 activation by IL-6 could reverse the phenotype and immunosuppression of Notch signalling-deficient MDSCs. Therefore, targeting Notch signalling may be an effective therapeutic strategy in tumour therapy.

[miR-135b promotes the invasion and metastasis of hepatocellular carcinoma cells].

OBJECTIVE: To explore the effect of miR-135b on the invasion and metastasis of hepatocellular carcinoma cells and the underlying molecular mechanism. METHODS: The invasive and metastasis abilities were detected by Transwell(TM) assay in hepatocellular carcinoma cells with over-expressed or down-regulated miR135b. The hepatocellular carcinoma cell growth and tumor formation abilities in vivo were examined by xenograft model. Downstream genes targeted by miR-135b were detected by Western blotting and dual-luciferase report assay. RESULTS: Up-regulated miR-135b was observed in highly invasive MHCC97 hepatocellular carcinoma cell lines. Over-expression of miR-135b enhanced the invasive and migratory abilities in vitro and in vivo of HepG2 and Bel-7402 cells. The invasive and migratory abilities in vitro and in vivo were significantly suppressed in miR-135b down-regulated MHCC97 hepatocellular carcinoma cells silenced by the pcDNA-miR-135b-Sponge plasmid. Western blotting and dual-luciferase report system analysis showed that multiple key components in the Hippo pathway, including large tumor suppressor homolog 2 (LATS2), beta-transducin repeats-containing proteins (ß-TrCP), N-myc downstream-regulated gene 2 (NDR2) as well as leucine zipper tumor suppressor gene 1 (LZTS1) were targeted by miR-135b. CONCLUSION: miR-135b promotes the invasion and metastasis possibly by targeting the Hippo pathway genes.

EGFR inhibitors and autophagy in cancer treatment.

Epidermal growth factor receptor (EGFR) inhibitor treatment is a strategy for cancer therapy. However, innate and acquired resistance is a major obstacle of the efficacy. Autophagy is a self-digesting process in cells, which is considered to be associated with anti-cancer drug resistance. The activation of EGFR can regulate autophagy through multiple signal pathways. EGFR inhibitors can induce autophagy, but the specific function of the induction of autophagy by EGFR inhibitors remains biphasic. On the one hand, autophagy induced by EGFR inhibitors acts as a cytoprotective response in cancer cells, and autophagy inhibitors can enhance the cytotoxic effects of EGFR inhibitors. On the other hand, a high level of autophagy after treatment of EGFR inhibitors can also result in autophagic cell death lacking features of apoptosis, and the combination of EGFR inhibitors with an autophagy inducer might be beneficial. Thus, autophagy regulation represents a promising approach for improving the efficacy of EGFR inhibitors in the treatment of cancer patients.

Cyclooxygenase-2 inhibitor is a robust enhancer of anticancer agents against hepatocellular carcinoma multicellular spheroids.

PURPOSE: Celecoxib, an inhibitor of cyclooxygenase-2 (COX2), was investigated for enhancement of chemotherapeutic efficacy in cancer clinical trials. This study aimed to determine whether celecoxib combined with 5-fluorouracil or sorafenib or gefitinib is beneficial in HepG2 multicellular spheroids (MCSs), as well as elucidate the underlying mechanisms. METHODS: The human hepatocellular carcinoma cell line HepG2 MCSs were used as in vitro models to investigate the effects of celecoxib combined with 5-fluorouracil or sorafenib or gefitinib treatment on cell growth, apoptosis, and signaling pathway. RESULTS: MCSs showed resistance to drugs compared with monolayer cells. Celecoxib combined with 5-fluorouracil or sorafenib exhibited a synergistic action. Exposure to celecoxib (21.8 µmol/L) plus 5-fluorouracil (8.1 × 10(-3) g/L) or sorafenib (4.4 µmol/L) increased apoptosis but exerted no effect on COX2, phosphorylated epidermal growth-factor receptor (p-EGFR) and phosphorylated (p)-AKT expression. Gefitinib (5 µmol/L), which exhibits no growth-inhibition activity as a single agent, increased the inhibitory effect of celecoxib. Gefitinib (5 µmol/L) plus celecoxib (21.8 µmol/L) increased apoptosis. COX2, p-EGFR, and p-AKT were inhibited. CONCLUSION: Celecoxib combined with 5-fluorouracil or sorafenib or gefitinib may be superior to single-agent therapy in HepG2 MCSs. Our results provided molecular evidence to support celecoxib combination-treatment strategies for patients with human hepatocellular carcinoma. MCSs provided a good model to evaluate the interaction of anticancer drugs.

[Effects of SIPL1 screened by suppression subtractive hybridization (SSH) on biological function and drug resistance of renal cell carcinoma cells].

OBJECTIVE: To screen the differentially expressed genes in human renal clear-cell carcinoma (RCC) cells using suppression subtractive hybridization (SSH), and to explore their biological function and underlying mechanism in RCC cells. METHODS: Total RNAs were extracted from human renal clear-cell carcinoma cell line RLC-310 and human normal renal cell line HK-2 cells, and SSH technology was used to construct a RCC cell library of differential expression genes and to screen the most differentially expressed genes. RNA interference vector was constructed to silence the expression of the differentially expressed gene SIPL1 in human renal cell lines RLC-310 and GRC-1. Proliferation index was estimated by cell counting, MTT and tumor xenograft assay. Cell cycle analysis was performed using fluorescence activated cell sorting. Drug resistance potential to adriamycin was assessed by MTT. RESULTS: A subtractive cDNA library of highly expressed genes in the RCC cells was constructed and 12 differentially expressed genes were screened from the subtractive library, in which SIPL1 was the most differently expressed gene in the RCC cell line. SIPL1 overexpression in the RCC cells and clinical samples was confirmed by RT-PCR and Western blot analyses. The shRNA expression plasmid targeting to SIPL1 gene was constructed and transfected into RLC-310 and GRC-1 cells, resulting in downregulation of SIPL1. SIPL1 knockdown inhibited the cell proliferation (P < 0.05) and tumorgenesis. The tumor weights formed by RLC-310 cells transfected with SIPL1 shRNA was (0.22 ± 0.07)g and that of negative control vector was (0.85 ± 0.06)g. The tumor weight formed by GRC-1 cells was (0.32 ± 0.07)g and that of control vectors was (1.21 ± 0.11)g (P < 0.05). SIPL1 shRNA-transfected RLC-310 cells showed that more cells were arrested at G0/G1 phase [(71.13 ± 4.58)%] than that in the negative control RLC-310 cells [(53.27 ± 3.34)%, P < 0.05]. The proportion of G0/G1 phase in the SIPL1 shRNA transfected GRC-1 cells was (73.83 ± 3.97)%, significantly higher than that of (59.33 ± 3.03)% in the negative control GRC-1 cells (P < 0.05), and enhanced their sensitivity to adriamycin (P < 0.05). Silence of SIPL1 caused inactivation of AKT signaling and up-regulated expression of P27(Kip1) and P21(Cip1) proteins. CONCLUSIONS: A differentially expressed gene SIPL1 in the renal clear-cell carcinoma is successfully screened using SSH technology. SIPL1 functions as an oncogene in RCC, and may become a novel molecular target for RCC diagnosis and therapy.

The photocatalytic activity of TiO2 thin film deposited on Al plate together with Cu(II) and Ag(I).

Cu (II) and Ag(I) together with TiO(2) powder were deposited on conducting support substrates to enhance the photocatalytic ability. The catalytic efficiency was tested by monitoring the photocatalytic degradation and detriment of methylene blue (MB) and bovine serum albumin (BSA). The conformational change of BSA induced by catalysts was also observed by circular dichroism spectroscopy.The antibacterial activities were studied by Escherichia coli. Both MB and BSA could be degraded more efficiently than pure TiO(2). After treatment with catalyst, the morphology of cells became twisted and rougher. Regular wrinkles were damaged and groove-like rift appeared on the surface. The fluorescence polarization has shown a significant decrease in membrane fluidity and the increase of permeability of cell membrane. Changes of the spectral profile of E. coli were observed, which suggested the damages of surface groups on the cell membrane.

Survival advantages of multicellular spheroids vs. monolayers of HepG2 cells in vitro.

Mammalian cells grow in three-dimensions (3-D) in vivo. Commonly used two-dimensional (2-D) cell cultures are inadequate to recreate the biological microenvironment of tumor cells. The potentially different outcomes from 2-D and 3-D culture systems may have a significant impact on the relevance of experimental findings. The purpose of this study was to characterize the human hepatoma cell line HepG2 in 2-D and 3-D cultures. HepG2 cells in 2-D and 3-D cultures were treated with cisplatin, 5-fluorouracil, and adriamycin and were analyzed by scanning electron microscopy and transmission electron microscopy. Cell cycle progression and apoptosis were detected by flow cytometry. Inhibition of cell proliferation was quantified by MTT assay. The expression of E-cadherin, CD44v6, VEGF, KDR, endostatin, Bax, and cytochrome-c were analyzed by immunohistochemical (IHC) staining. As compared to the 2-D monolayer culture, the 3-D multicellular spheroids (MCS) of HepG2 cells featured a greater fraction of cells in G1 phase and were organized with more abundant cell-cell adhesion. In addition, cells in MCS were significantly less apoptotic in maintenance culture media and were more resistant to drug-induced apoptosis. E-cadherin, CD44v6, VEGF, KDR, endostatin, and cytochrome-c levels were increased in MCS as compared to 2-D cell cultures. In conclusion, MCS conferred differentiated phenotypes including increased cell-cell adhesion and G1 phase cell cycle arrest, enhanced cellular resistance to apoptosis, and upregulated angiogenic potential. Based on our data, a multicellular morphological hierarchy may sustain the growth/survival advantages of cancer cells in vivo. Therefore, a 3-D culture system should be the preferred technique for cancer biology investigation.

Chinese medicinal compound delisheng has satisfactory anti-tumor activity, and is associated with up-regulation of endostatin in human hepatocellular carcinoma cell line HepG2 in three-dimensional culture.

AIM: To investigate the multicellular resistance of human hepatocellular carcinoma HepG2 cells in three-dimensional culture to delisheng, 5-fluorouracil and adriamycin, and the possible molecular mechanisms of delisheng. METHODS: Human hepatocellular carcinoma HepG2 cells were cultured with a liquid overlay technique. After the formation of multicellular spheroids, morphology was analyzed by phase contrast microscopy, scanning electron microscopy and transmission electron microscopy. Sensitivity of HepG2 cells to delisheng, 5-fluorouracil and adriamycin was investigated by MTT assay in multicelluar spheroids and monolayers. Vascular endothelial growth factor (VEGF) and endostatin expression were analyzed in multicellular spheroids treated with delisheng, 5-fluorouracil, adriamycin and negative control PBS, with immunohistochemical staining. RESULTS: Multicellular spheroids exhibited structural characteristics somewhat different to those in monolayers. The cells in three-dimensional cell culture turned out to be less sensitive to delisheng, 5-fluorouracil and adriamycin than the cells cultured in monolayer. This showed that delisheng had a satisfactory cells inhibition ratio compared to 5-fluorouracil and adriamycin. Immunohistochemical staining showed that VEGF and endostatin expression was positive during growth as multicellular spheroids, and endostatin expression in spheroids with treatment of delisheng was higher than that with 5-fluorouracil, adriamycin and PBS (139.35 +/- 7.83, 159.23 +/- 10.34, 162.83 +/- 3.47 and 148.48 +/- 11.06, P < 0.05). CONCLUSION: Chinese medicine compound delisheng has satisfactory anti-tumor activity in HepG2 cells in three-dimensional culture, and the effects are associated with up-regulation of endostatin.