Andrographolide sensitizes KRAS-mutant colorectal cancer cells to cetuximab by inhibiting the EGFR/AKT and PDGFRß/AKT signaling pathways.

BACKGROUND: Cetuximab, an inhibitor targeting EGFR, is widely applied in clinical management of colorectal cancer (CRC). Nevertheless, drug resistance induced by KRAS-mutations limits cetuximab's anti-cancer effectiveness. Furthermore, the persistent activation of EGFR-independent AKT is another significant factor in cetuximab resistance. Nevertheless, the mechanism that EGFR-independent AKT drives cetuximab resistance remains unclear. Thus, highlighting the need to optimize therapies to overcome cetuximab resistance and also to explore the underlying mechanism. PURPOSE: This work aimed to investigate whether and how andrographolide enhance the therapeutic efficacy of cetuximab in KRAS-mutant CRC cells by modulating AKT. METHODS: The viabilities of CRC cell lines were analyzed by CCK-8. The intracellular proteins phosphorylation levels were investigated by Human Phospho-kinase Antibody Array analysis. Knockdown and transfection of PDGFRß were used to evaluate the role of andrographolide on PDGFRß. The western blotting was used to investigate Wnt/ß-catenin pathways, PI3K/AKT, and EMT in KRAS-mutant CRC cells. The animal models including subcutaneous tumor and lung metastasis were performed to assess tumor response to therapy in vivo. RESULTS: Andrographolide was demonstrated to decrease the expression of PI3K and AKT through targeting PDGFRß and EGFR, and it enhanced cetuximab effect on KRAS-mutant CRC cells by this mechanism. Meanwhile, andrographolide helped cetuximab to inhibit Wnt/ß-catenin, CRC cell migration and reduced Vimentin expression, while increasing that of E-cadherin. Lastly, co-treatment with cetuximab and andrographolide reduced the growth of KRAS-mutant tumors and pulmonary metastases in vivo. CONCLUSIONS: Our findings suggest that andrographolide can overcome the KRAS-mutant CRC cells' resistance to cetuximab through inhibiting the EGFR/PI3K/AKT and PDGFRß /AKT signaling pathways. This research provided a possible theory that andrographolide sensitizes KRAS-mutant tumor to EGFR TKI.

Numerical simulation of mechanical tests on a living skin using anisotropic hyperelastic law.

The skin is a living tissue that behaves in a hyperelastic and anisotropic way. A constitutive law called HGO-Yeoh is proposed to model the skin by improving the classical HGO constitutive law. This model is implemented in a finite element code FER "Finite Element Research" to benefit from its tools, including the bipotential contact method, a very efficient function coupling contact and friction. Identifying the skin-related material parameters is done through an optimisation procedure using analytic and experimental data. A tensile test is simulated using the codes FER and ANSYS. Then, the results are compared with the experimental data. Finally, a simulation of an indentation test using a bipotential contact law is done.

Enhanced segmentation of gastrointestinal polyps from capsule endoscopy images with artifacts using ensemble learning.

BACKGROUND: Endoscopy artifacts are widespread in real capsule endoscopy (CE) images but not in high-quality standard datasets. AIM: To improve the segmentation performance of polyps from CE images with artifacts based on ensemble learning. METHODS: We collected 277 polyp images with CE artifacts from 5760 h of videos from 480 patients at Guangzhou First People's Hospital from January 2016 to December 2019. Two public high-quality standard external datasets were retrieved and used for the comparison experiments. For each dataset, we randomly segmented the data into training, validation, and testing sets for model training, selection, and testing. We compared the performance of the base models and the ensemble model in segmenting polyps from images with artifacts. RESULTS: The performance of the semantic segmentation model was affected by artifacts in the sample images, which also affected the results of polyp detection by CE using a single model. The evaluation based on real datasets with artifacts and standard datasets showed that the ensemble model of all state-of-the-art models performed better than the best corresponding base learner on the real dataset with artifacts. Compared with the corresponding optimal base learners, the intersection over union (IoU) and dice of the ensemble learning model increased to different degrees, ranging from 0.08% to 7.01% and 0.61% to 4.93%, respectively. Moreover, in the standard datasets without artifacts, most of the ensemble models were slightly better than the base learner, as demonstrated by the IoU and dice increases ranging from -0.28% to 1.20% and -0.61% to 0.76%, respectively. CONCLUSION: Ensemble learning can improve the segmentation accuracy of polyps from CE images with artifacts. Our results demonstrated an improvement in the detection rate of polyps with interference from artifacts.

Disruption of O-GlcNAcylation Homeostasis Induced Ovarian Granulosa Cell Injury in Bovine.

O-linked ß-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. However, little information is available regarding the molecular regulation of O-GlcNAcylation in granulosa cell function and glucose metabolism. This study focused on the impact of disrupted O-GlcNAc cycling on the proliferation and apoptosis of bovine granulosa cells, and further aimed to determine how this influenced glucose metabolism. Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. Dysregulated O-GlcNAc cycling reduced cell viability, downregulated the proliferation-related genes of CDC42 and PCNA transcripts, upregulated the pro-apoptotic genes of BAX and CASPASE-3 mRNA and the ratio of BAX/BCL-2, and increased the apoptotic rate. Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. Moreover, inhibition of OGT significantly increased the expression level of thioredoxin-interacting protein (TXNIP), but repression of OGA had no effect. Collectively, our results suggest that perturbation of O-GlcNAc cycling has a profound effect on granulosa cell function and glucose metabolism.

Characterizing the composition of intestinal microflora by 16S rRNA gene sequencing.

BACKGROUND: This study determined the composition and diversity of intestinal microflora in patients with colorectal adenoma (CRA), which may provide precedence for investigating the role of intestinal microflora in the pathogenesis of colorectal tumors, the composition of intestinal microflora closely related to CRA, and further validating the possibility of intestinal flora as a biomarker of CRA. AIM: To study the relationship between intestinal microflora and CRA. METHODS: This is a prospective control case study from October 2014 to June 2015 involving healthy volunteers and patients with advanced CRA. High-throughput sequencing and bioinformatics analysis were used to investigate the composition and diversity of intestinal microflora in 36 healthy subjects and 49 patients with advanced CRA. Endpoints measured were operational taxonomic units of intestinal flora, as well as their abundance and diversity (α and ß types). RESULTS: In this study, the age, gender, body mass index, as well as location between controls and patients had no significant differences. The mucosa-associated gut microbiota diversity and bacterial distribution in healthy controls and colorectal adenomas were similar. The operational taxonomic unit, abundance, and α and ß diversity were all reduced in patients with CRA compared to controls. At the phylum level, the composition of intestinal microflora was comparable between patients and controls, but the abundance of Proteobacteria was increased, and Firmicutes and Bacteroides were significantly decreased (P < 0.05). The increase in Halomonadaceae and Shewanella algae, and reduction in Coprococcus and Bacteroides ovatus, could serve as biomarkers of CRA. High-throughput sequencing confirms the special characteristics and diversity of intestinal microflora in healthy controls and patients with CRA. CONCLUSION: The diversity of intestinal microflora was decreased in patients with CRA. An increase in Halomonadaceae and Shewanella algae are markers of CRA.

Bioinformatics Analysis and RNA-Sequencing of SCAMP3 Expression and Correlated Gene Regulation in Hepatocellular Carcinoma.

BACKGROUND: Secretory Carrier Membrane Proteins 3 (SCAMP3) is a transmembrane protein that affects intracellular trafficking, protein sorting and vesicle formation. Overexpression of SCAMP3 correlates with poorly differentiated hepatocellular carcinoma (HCC). However, the expression and corresponding gene regulation of SCAMP3 in HCC remain unclear. METHODS: Bioinformatics analyses of clinical parameters and survival data were conducted to predict the prognostic value of SCAMP3 in HCC. RNA sequencing and real-time PCR were conducted to confirm the SCAMP3 expression in HCC tissue. Expression was analyzed using OncomineTM and UALCAN, while SCAMP3 alterations and survival analysis were identified by cBioPortal. Differential gene expression with SCAMP3 was analyzed by LinkedOmics and GEPIA. The target networks of enzymes and co-transcriptional factors were identified using Gene enrichment analysis. Expression of SCAMP3 in HCC tissue was detected by RNA-sequencing and Western-blotting. RESULTS: Based on bioinformatics analysis and detection of mRNA expression, SCAMP3 was over-expressed in numerous tumors, especially in HCC. SCAMP3 level was positively correlated with disease stages and tumor grades and negatively correlated with patient survival. Furthermore, functional network analysis indicated that SCAMP3 regulated metabolic process and DNA replication through oxidative phosphorylation and chromatin remodeling or Ribosome. SCAMP3 regulated a number of gene expressions including PPAP2B, SNRK, ARID4A, PRCC, VPS72 via protein binding and proteasome, which may affect cell adhesion, proliferation, transcription, cell cycle and metabolism. Further, Real-time PCR and Western-blotting showed that the SCAMP3 level was increased in HCC tissue. CONCLUSION: The present data analysis efficiently reveals information about SCAMP3 expression and correlated function in HCC, laying a foundation for further study of SCAMP3 in the tumor.

Survey of antibiotic use among hospitalised children in a hospital in Northeast China over a 4-year period.

PURPOSE: We investigated the usage of antibiotic utilisation rate (AUR) among Chinese hospitalised children over a 4-year period to determine clinical characteristics. DESIGN AND METHODS: AUR, antibiotic type and antibiotic use in combination were analysed among hospitalised children of the affiliated hospital of Beihua University in Northeast China from January 2015 to December 2018. The linear prediction was used to investigate the trends of antibiotics use in combination and AUR, and autoregressive integrated moving average model was used to predict AUR in 2019. RESULTS: A total of 2,981 inpatients were admitted to the hospital during the study period. The AUR from 2015 to 2018 was 91.51%, 92.67%, 91.30%, and 93.00%, respectively. AUR was associated with season (p < .01), the peak period was found to be from November to January in 2019 (R2 = 0.802). The etiological delivery rate had increased (p < .01). Pneumonia was the main disease in children for which they received antibiotics. The combination of multidrug (≥3 agents used) had increased (p < .01) over the study period. PRACTICE IMPLICATIONS: AUR was stable among hospitalised children in a hospital. Cephalosporin and macrolide antibiotics were the main antibiotic types, and the combination of multidrug had increased, more attention should be paid to the use of antibiotics in hospitalised children.

TK1 overexpression is associated with the poor outcomes of lung cancer patients: a systematic review and meta-analysis.

AIM: The study aimed to unveil the effect of TK1 expression on the clinicopathological significance and prognosis in patients with lung cancer. Results & methodology: Studies for meta-analysis were selected according to a thorough literature search in databases (PubMed, EMBASE and Chinese databases). Ten studies containing 1393 lung cancer patients were investigated in our analysis. The TK1 overexpression was associated with poorer overall survival(OS) in lung cancer patients (hazard ratio = 1.881; 95% CI:1.318-2.684, Z = 3.48; p = 0.001). Furthermore, The TK1 expression is associated with the clinicopathological features of lung cancer patients (tumor type, age, lymph node metastasis, distant metastasis and tumor, node, metastasis [TNM] stages).  Discussion & conclusion: The TK1 expression might have a supportive implication in assessing biological behavior and prognosis of lung cancer patients.

[Low cement distribution index is a risk factor for refracture of the adjacent segments after percutaneous vertebroplasty].

OBJECTIVE: To investigate the impact of cement distribution index on the occurrence of refracture in the adjacent segments after percutaneous vertebroplasty. METHODS: This retrospective analysis was conducted among 143 patients who received percutaneous vertebroplasty for osteoporotic vertebral compression fracture between April, 2011 and April, 2014. Of the 134 patients with complete follow-up data, 18 had adjacent segment fracture within 1 year following the surgeries (re-fracture group), and 116 patients without new fracture served as the control group. All the patients underwent X-ray examinations after the surgery and according to the position and shape, the cement in the vertebrae were classified into 5 types (I to V), and the volume-cubage index was computed based on the cement volume and vertebral cubage. Age, gender, bone mineral density (BMD), cement distribution index, volume-cubage index, and cement leakage were evaluated in the 2 groups, and the variables with significant differences between the 2 groups were analyzed in Logistic regression analysis. RESULTS: BMD was significantly lower and the rate of cement leakage was significantly higher in the re-fracture group than in the control group (P<0.05). Significant difference was found in cement distribution index between the 2 groups (P<0.05) but not in age, gender, cement volume or volume-cubage index (P>0.05). Logistic regression analysis indicated that BMD, cement leakage and cement distribution index all significantly affected the occurrence of adjacent vertebral fractures following percutaneous vertebroplasty. CONCLUSION: A low BMD, cement leakage and a low cement distribution index are all risks factor of adjacent vertebral fracture after percutaneous vertebroplasty.

NIMA-related kinase 2 regulates hepatocellular carcinoma cell growth and proliferation.

NIMA-related kinase 2 (Nek2) is often upregulated in human cancer and is important in regulating the cell cycle and gene expression, and maintaining centrosomal structure and function. The present study aimed to investigate the expression pattern, clinical significance, and biological function of Nek2 in hepatocellular carcinoma (HCC). mRNA and protein levels of Nek2 were examined in HCC and corresponding normal liver tissues. The MTT and soft agar colony formation assays, and flow cytometry were employed to assess the roles of Nek2 in cell proliferation and growth. In addition, western blot analysis was performed to assess the expression of cell cycle- and proliferation-related proteins. The results revealed that Nek2 was upregulated in HCC tissues and cell lines. The clinical significance of Nek2 expression was also analyzed. Inhibiting Nek2 expression by siRNA suppressed cell proliferation, growth, and colony formation in hepatocellular carcinoma cell line HepG2 cells, induced cell cycle arrest in the G2/M phase by retarding the S-phase, and promoted apoptosis. Furthermore, Nek2 depletion downregulated ß-catenin expression in HepG2 cells and diminished expression of Myc proto-oncogene protein (c-Myc), cyclins D1, B1, and E and cyclin-dependent kinase 1, whilst increasing protein levels of p27. This demonstrates that overexpression of Nek2 is associated with the malignant evolution of HCC. Targeting Nek2 may inhibit HCC cell growth and proliferation through the regulation of ß-catenin by the Wnt/ß-catenin pathway and therefore may be developed as a novel therapeutic strategy to treat HCC.

Case History Report: Cone Beam Computed Tomography for Implant Insertion Guidance in the Presence of a Dense Bone Island.

This article describes the use of cone beam computed tomography (CBCT) to diagnose a dense bone island (DBI) to facilitate implant insertion guidance in a patient followed up for 4 years. Suitable image-directed preplanning and periodic review by CBCT scanning is recommended when a jaw DBI is encountered in treatment planning for implant placement.

Synthesis, Anti-inflammatory Activities and Mechanisms of 3,5- dihydroxycinnamic Acid Derivatives.

BACKGROUND: 3,4-dihydroxycinnamic acid and its derivatives exhibit numerous biologic activities. Such activities have not previously been reported for 3,5-dihydroxycinnamic acid derivatives. In this study, ten derivatives of 3,5- dihydroxycinnamic acid were synthesized and their anti-inflammatory activities were tested in 12-O-tetradecanoylphorbol 13-acetate-induced mouse ear edema. Molecular biological studies have shed lights on their anti-inflammatory mechanism. METHODS: Anti-inflammatory activities of ten new synthesized derivatives of 3,5-dihydroxycinnamic acid were tested in 12-O-tetradecanoylphorbol 13-acetate-induced mouse ear edema, and their anti-inflammatory mechanism was studied by ELISA, real-time RT-PCR, MPO assay and AA-induced mouse ear edema. RESULTS: Compound 7 showed a pronounced anti-inflammatory effect and the inhibition rate was 65.6% at a dose of 1.6mg/ear. This compound acted by reducing mRNA and protein synthesis of tumor necrosis factor-α, interleukins 1ß and 6, and also by decreasing the levels of activated neutrophil infiltrates. Furthermore, compound 7 significantly suppressed arachidonic acid-induced edema as well. Cell-based assays showed that compound 7 inhibited the production of cyclooxygenase- 2-catalyzed prostaglandin E2 from lipopolysaccharide-treated RAW 264.7 cells, and also inhibited 5-lipoxygenase production from A23187-treated RBL-1 cells, and consequently reduced leukotriene B4 production. CONCLUSION: This investigation revealed that some of the derivatives of 3,5-dihydroxycinnamic acid exhibit a more pronounced anti-inflammatory effect than 3,4-dihydroxycinnamic acid. Therefore, 3,5-dihydroxycinnamic acid derivatives, especially compound 7, represent potential value for antiinflammatory drug development.

[The anti-tumor activity and molecular mechanisms of an Aurora kinase inhibitor ZLJ213 in suppressing colon cancer growth].

The aim of this study is to evaluate anti-tumor activities and mechanism of a novel kinase inhibitor ZLJ213 which targeted Aurora A and vascular endothelial growth factor receptor (VEGFR) in vitro and in vivo against human colon cancer. Results showed that ZLJ213 inhibited cell proliferation and induced cell cycle arrest and apoptosis of HCT1 16 and SW48 cell lines. In HCT116-derived xenograft, ZLJ213 dosed at 100 mg · kg(-1) inhibited tumor growth by 73.24%. The IC50 of ZLJ213 on the expression of p-Aurora A was 0.258 µmol · L(-1) analyzed by ELISA. Under the concentration of 0.08 µmol · L(-1), ZLJ213 could inhibit the activities of Aurora A, Histone H3 and VEGFR of HCT116 and SW48 cell lines. Simultaneously, ZLJ213 induced activation of Caspase 3 and PARP cleavage. Above data suggested that ZLJ213 had the ability to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo in colon cancer, and down-regulate the expression of p-Aurora A and p-VEGFR. ZLJ213 might be a potential therapeutic agent against colon cancer.

Low G preconditioning reduces liver injury induced by high +Gz exposure in rats.

AIM: To investigate the effect of repeated lower +Gz exposure on liver injury induced by high +Gz exposure in rats. METHODS: Sixty male Wister rats were randomly divided into a blank control group, a low G preconditioning group (LG) (exposed to +4 Gz/5 min per day for 3 d before +10 Gz/5 min exposure), and a +10 Gz/5 min group (10G) (n = 20 in each group). Blood specimens and liver tissue were harvested at 0 h and 6 h after +10 Gz/5 min exposure. Liver function was analyzed by measuring serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, and liver injury was further assessed by histopathological observation. Malondialdehyde (MDA), superoxide dismutase (SOD) and Na(+)-K(+)-ATPase were determined in hepatic tissue. RESULTS: The group LG had lower ALT, AST, and MDA values at 0 h after exposure than those in group 10G. SOD values and Na(+)-K(+)-ATPase activity in the LG group were higher than in group 10G 0 h post-exposure. Hepatocyte injury was significantly less in group LG than in group 10G on histopathological evaluation. CONCLUSION: It is suggested that repeated low +Gz exposure shows a protective effect on liver injury induced by high +Gz exposure in rats.

Synergistic effect of RhBMP-2 and bFGF on ectopic osteogenesis in mice.

OBJECTIVE: To investigate the synergistic effect and mechanism of the combined application of recombinant human bone morphogenetic protein-2 (rhBMP-2) and basic fibroblast growth factor (bFGF). METHODS: 24 KM male mice were randomly divided into 6 groups with 4 mice in each group, namely, Group A (control group), Group B (only treated with collagen), Group C (treated with 2 ng bFGF+collagen), Group D (treated with 4 µ g rhBMP-2+collagen), Group E (treated with 4 µ g rhBMP-2+2 ng bFGF+collagen) and Group F (treated with 4 µ g rhBMP-2+4 ng bFGF+collagen). The composites were implanted into the intermuscular septum of hind legs mice; whereas in control group, intermuscular septum of mice was separated and no implantation was performed. General observation, detection of concentration of calcium content, micro computed tomography (Micro-CT), three-dimensional reconstruction scan, measurement of bone mineral density (BMD), bone volume fraction (BVF) and trabecular thickness (Tb.Th), as well as histological observation with HE staining and ALP and CD34 immumohistochemical staining were performed. RESULTS: Ectopic osteogenesis was found in Groups D, E and F mice. The difference in concentration of calcium contents was statistically significant between Groups D and E (P<0.05), but insignificant between Groups E and F (P>0.05). Micro-CT and three-dimensional reconstruction revealed continuous newborn bone substance in external surface of ectopic bone formation, and the center of bone formation did not show obvious substantial filling by bone substance. The differences in BMD, BVF and Tb.Th were statistically significant between Groups D and E or F (P<0.01 or <0.05). HE staining showed that in Groups D, E and F, newborn bone substance was mainly located at the edge of ectopic bone formation, and the bone formation in Groups E and F was better than that in Group D. ALP and CD34 immumohistochemical staining revealed the positive expression mainly at the edge of ectopic bone formation, and area of positive expression in Groups E and F was larger than that in Groups D. CONCLUSIONS: rhBMP-2 possesses the capacity to induce ectopic osteogenesis independently, but bFGF does not have this ability; the combined application of rhBMP-2 and bFGF can enhance the synergetic effect on inducing ectopic osteogenesis.

Antigen-extracted xenogeneic cancellous bone graft with recombinant human bone morphogenetic protein-2 enhances bone regeneration in repair of mandibular defect in rabbits.

The effects of a large-piece of xenogeneic bone that was separated from healthy pigs as a scaffold for the repair of a mandibular defect was investigated, and the applicability of antigen-extracted xenogeneic cancellous bone (AXCB) soaked with recombinant human bone morphogenetic protein-2 (rhBMP-2) in bone defect repair was assessed. Mandibular defects were created in 48 New Zealand rabbits, and the animals were randomly divided into four groups, in which the mandibular defects were grafted with AXCB, AXCB soaked with rhBMP-2, and autograft bone, or left blank. An equal number of animals from each group were classified into three time points (4, 8, and 12 weeks) after surgery for gross pathological observation, hematoxylin and eosin (H and E) staining, radiographic examination, and bone density measurement. H and E staining revealed that the area percentage of bone regeneration in the group of the AXCB/rhBMP-2 graft was 27.72 ± 4.68, 53.90 ± 21.92, and 77.35 ± 9.83 at 4 weeks, 8 weeks, and 12 weeks, respectively. These results were better than those of the autogenous bone graft, suggesting that the group of the AXCB/rhBMP-2 graft achieved a good osteogenic effect. With regard to the AXCB graft without rhBMP-2, the area percentage of bone regeneration was only 14.03 ± 5.02, 28.49 ± 11.35, and 53.90 ± 21.92. Therefore, the osteogenic effect of the AXCB/rhBMP-2 graft was demonstrated to have the best effect. In the group of the AXCB/rhBMP-2 graft, the area percentage of bone regeneration increased, and the implanted materials were gradually degraded and replaced by autogenous bone regeneration over time. We conclude that the AXCB graft soaked with rhBMP-2 showed good osteogenic effect in the repair of bone defects and good biocompatibility. AXCB serves as a good carrier of rhBMP-2, which promotes bone formation.

Female patient-specific finite element modeling of pelvic organ prolapse (POP).

Pelvic organ prolapse (POP) occurs only in women and becomes more common as women age. However, the surgical practices remain poorly evaluated. The realization of a simulator of the dynamic behavior of the pelvic organs is then identified as a need. It allows the surgeon to estimate the functional impact of his actions before his implementation. In this work, the simulation will be based on a patient-specific approach in which each geometrical model will be carried out starting from magnetic resonance image (MRI) acquisition of pelvic organs of one patient. To determine the strain and stress in the soft biological tissues, hyperelastic constitutive laws are used in the context of finite element analysis. The Yeoh model has been implemented into an in-house finite element code FER to model these organ tissues taking into account large deformations with multiple contacts. The 2D and 3D models are considered in this preliminary study and the results show that our method can help to improve the understanding of different forms of POP.

[Synthesis of novel curcumin mimics and preliminary evaluation for their antitumor activity].

Curcumin has been reported to possess antitumor activity with low toxicity. However, the clinical application of curcumin has been significantly limited by its instability and poor metabolic property. In order to overcome these limitations and discover novel small molecules with potential antitumor activity, 29 curcumin mimics were synthesized, which were confirmed by 1H NMR and HR-MS, and their cytotoxic property was evaluated against five human cancer cell lines in vitro. Compounds 16, 18 and 19 exhibited good cytotoxic property, their IC50 value were even below 5 micromol x L(-1) to some cancer cell lines, 5-9 times better than curcumin.

[Anti-tumor activity and mechanism of T03 in vitro and in vivo].

The purpose of this study is to investigate the activity and mechanism of a new anti-tumor agent T03. MTT and colony formation assay were performed to determine anti-proliferation activity of T03 in vitro. Antitumor activity was observed by Renca xenograft model in vivo. The effect of T03 on cell cycle and apoptosis were measured by FCM analysis. Western blotting was performed to investigate the expression level of proteins in HepG2 cell lines treated with T03. T03 had anti-tumor activity by inhibiting tumor cell growth and colony formation in vitro, especially on hepatocellular carcinoma cells (HCC). At the concentration of 10 micromol x L(-1), T03 induced cell apoptosis and cell cycle arrest in HCC. Moreover, it proved that T03 reduced the tumor weight with the rate of 42.30% without any obviously side effect in Renca xenograft model. At the concentration of 2.0 micromol x L(-1), T03 was able to reduce the level of p-c-Raf (Ser259), and thus blocked Raf/MEK/ERK and AKT signaling in HepG2 cell lines. The result suggested that T03 has the potential to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo, particularly active against HCC, indicating T03 and its analogues may serve as a new anti-cancer drug against hepatocellular carcinoma.

[Synthesis and biological evaluation of 2-(3-butynoicamidophenyl) benzothiazole derivatives as antitumor agents].

A series of 2-(3-butynoicamidophenyl)benzothiazole derivatives were synthesized starting from 4-fluoro-3-nitrobenzoic acid. Structures of all the synthesized compounds were confirmed by 1H NMR and HR-MS. Their antitumor activities against human tumor cells lines (HCT116, Mia-PaCa2, U87-MG, A549, NCI-H1975) were evaluated by MTT assay. The results revealed that most of the synthesized compounds showed potent activities against HCT116, Mia-PaCa2, U87-MG tumor cells lines. Particularly, compounds 14c and 14h exhibited better activity with IC50 values of 1 x 10(-8) mol x L(-1) against U87-MG and HCT116 respectively. The structure-activity relationship of compounds was also discussed preliminarily.