Succinic acid inhibits photosynthesis of Microcystis aeruginosa via damaging PSII oxygen-evolving complex and reaction center.

To elucidate the mechanism of succinic acid (SA) inhibition of Microcystis aeruginosa, the chlorophyll fluorescence transients, photosynthesis, photosynthetic electron transport activity, and gene expression of M. aeruginosa were evaluated under various doses of SA. The results demonstrated that, after treatment with 60 mg L-1 SA for 1 h, the chlorophyll fluorescence transients and related parameters changed significantly, indicating that the function and structure of photosynthetic apparatuses of Microcystis were seriously damaged. The initial quantum efficiency α, maximum net photosynthetic rate Pnmax, dark respiration rate Rd, and gross photosynthetic rate decreased to 57%, 49%, 49%, and 46%, respectively, relative to the control. Furthermore, photosystem II (PSII) activity (H2O→p-BQ) and the electron transport activity of H2O→MV and DPC→MV significantly decreased. Real-time PCR analysis revealed that, following incubation with 60 mg L-1 SA for 24 h, the expression level of core protein genes (psbA, psaB, psbD, and psbO) of the photosynthesis centers photosystem I (PSI) and PSII decreased significantly. However, the transcription of gene nblA encoding phycobilisome degradation protein was elevated. The downregulation of the rbcL gene, which encodes the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), resulted in the suppression of CO2 fixation and assimilation. High concentration (60 mg L-1) of SA resulted in damage to oxygen-evolving complex (OEC) and reaction center of PSII, blocking photosynthetic electron transport, thereby lowering the rate photosynthesis and inhibiting the growth of Microcystis. We concluded that inhibition of photosynthesis is an important mechanism of SA inhibition in M. aeruginosa.

Ginkgetin alleviates high glucose-evoked mesangial cell oxidative stress injury, inflammation, and extracellular matrix (ECM) deposition in an AMPK/mTOR-mediated autophagy axis.

Diabetic nephropathy constitutes the leading cause for end-stage kidney disease. Ginkgetin is a common natural non-toxic biflavone and fulfills pleiotropic pharmacological characterizations, such as anti-inflammation and kidney injury. Nevertheless, its efficacy in diabetic nephropathy remains elusive. Here, ginkgetin exhibited little cytotoxicity in glomerular mesangial cells. Of note, ginkgetin restrained high glucose (HG)-induced mesangial cell proliferation and oxidative stress by inhibiting ROS and malonaldehyde levels, but enhancing antioxidant SOD activity. Additionally, ginkgetin suppressed HG-evoked transcript and release of inflammatory cytokine TNF-α, IL-1ß, and IL-6. Concomitantly, the increased extracellular matrix (ECM) deposition in HG-treated glomerular mesangial cells was attenuated by ginkgetin via decreasing expression of collagen IV, fibronectin, and laminin. Intriguingly, ginkgetin-restored HG-impaired autophagy; whereas blocking autophagy by its inhibitor 3-MA overturned ginkgetin function against HG-evoked mesangial cell dysfunction. Mechanistically, ginkgetin-mediated AMPK/mTOR axis accounted for HG-impaired autophagy. Importantly, blockage of AMPK signaling reversed ginkgetin-restored autophagy and its protective efficacy against HG-induced dysfunction in mesangial cells. Thus, these findings highlight that ginkgetin may attenuate HG-evoked mesangial cell hyperplasia, oxidative stress, inflammation, and ECM accumulation by activating AMPk/mTOR-mediated autophagy pathway. Therefore, ginkgetin may alleviate the progression of diabetic nephropathy by regulating glomerular mesangial cell dysfunction, supporting a promising therapeutic agent against diabetic nephropathy.

Cadmium phytotoxicity, related physiological changes in Pontederia cordata: antioxidative, osmoregulatory substances, phytochelatins, photosynthesis, and chlorophyll fluorescence.

Pontederia cordata is a heavy metal accumulator, while the heavy metal tolerance mechanisms of this plant are not well understood. Hydroponic experiments were used to assess the effects of Cd2+ on antioxidative activities, osmoregulatory substances and photosynthesis in leaves. Exposure of 5 mg L-1 Cd2+ for 7 days, the photosynthetic apparatus functioned normally and sustained a relatively high photosynthetic rate, and good growth was observed. Under 50 and 75 mg L-1 Cd2+, accelerated lipid peroxidation and increased peroxidase activity (POD; E.C.1.11.1.7) were detected, while no significant differences were observed in superoxide dismutase (SOD; E.C.1.15.1.1) and catalase (CAT; E.C.1.11.1.6) activities, as well as in lutein, ascorbic acid, and glutathione contains of leaves. Proline content increased, while soluble sugar and soluble protein contents decreased under 75 mg L-1 Cd2+. Cd2+ at different concentrations induced a reduction in carotenoid, total carotenoid, and ascorbic acid-dehydroascorbate contents. A significant increase in phytochelatin content was induced by 75 mg L-1. Chlorophyll content decreased under Cd stress and disturbed photosynthesis, causing dramatic reductions in photosynthetic parameters. Stomatal closure was responsible for a reduced photosynthetic rate under Cd2+ exposure. Cd2+ concentrations of no less than 25 mg L-1 disorganized the photosynthetic apparatus, induced the partial closure, and decreased activity of the photosystem II (PS II) reaction center, thus disturbing light conversion and utilization, thereby decreasing the photosynthetic efficiency in PS II.

Ecdysterone Accelerates Healing of Radiation-Induced Oral Mucositis in Rats by Increasing Matrix Cell Proliferation.

Development of oral mucositis represents a rate-limiting factor in radiation therapy for the treatment of head and neck, as well as other cancers. In this work, we investigated the treatment effect of ecdysterone (a steroid derived from the dry root of Achyranthes bidentate) on radiation-induced oral mucositis, and examined possible underlying mechanisms. Male Sprague-Dawley rats were exposed to 20 Gy X-ray irradiation (single dose, cranial localization) to induce oral mucositis. Possible therapeutic effects of ecdysterone on radiation-induced oral mucositis were investigated by monitoring weights, direct observations, visual scoring method and evaluation of hematoxylin and eosin staining. Assessments of leukocyte common antigen and proliferating cell nuclear antigen staining were also performed in the damaged areas of tongues harvested after irradiation, and changes in signaling pathways were investigated using Western blotting. The development and progression of radiation-induced oral mucositis in this model was similar to that observed in clinic patients. Ecdysterone effectively improved radiation-induced oral mucositis as assessed by direct observation and histopathology, and also increased proliferation of matrix cells, since the Ras-Raf-ERK signal pathway was found to be activated by its use. It was concluded that orally administered ecdysterone accelerated the healing process in a rat model of radiation-induced oral mucositis by upregulating the Ras-Raf-ERK signal pathway.

Tolerance mechanism of Triarrhena sacchariflora (Maxim.) Nakai. seedlings to lead and cadmium: Translocation, subcellular distribution, chemical forms and variations in leaf ultrastructure.

Hydroponic experiments were conducted to assess the accumulation, translocation, and chemical forms of lead (Pb) and cadmium (Cd) in the roots, stems, and leaves of Triarrhena sacchariflora seedlings and the associated variation in leaf ultrastructure. The leaves and leaf ultrastructure showed no significant symptoms of toxicity with 0.05 mM Pb or 0.01 mM Cd exposure for 10d. Chlorosis and wilting were observed in leaves when the Pb and Cd concentration was higher than 0.1 and 0.05 mM in the medium, respectively, as demonstrated by severe ultrastructural modifications at higher concentration in the leaves, such as plasmolysis, cell wall detachment, chloroplast swelling, nuclear condensation, and even nuclear fragmentation. The Pb and Cd concentrations in the roots was significantly higher than those in the stems and leaves. This indicated low Pb and Cd translocation from the roots to the aboveground parts. Subcellular distribution analysis showed that the majority of Pb and Cd was bound to the cell wall, especially in the roots, indicating that the cell wall likely constitutes a crucial storage site for Pb and Cd. This mechanism decreases the translocation of Pb and Cd across membranes and is more effective than vacuolar compartmentation. The majority of Pb and Cd exited in form of insoluble Pb/Cd-pectate or -oxalate complexes in the plant. In conclusion, higher concentrations of Pb or Cd induced premature senescence. High Pb and Cd enrichment was observed in the roots, which decreased the translocation of Pb and Cd from the roots to the aboveground tissues. The immobilization of Pb or Cd by the cell wall is important for plant detoxification and can protect protoplasts from Pb or Cd toxicity. Pb and Cd mainly existed in insoluble Pb/Cd-phosphate or -oxalate complexes, exhibiting low activity and thereby limiting symplastic transport and suppressing toxicity.

[Research progress on bisphosphonate-related osteonecrosis of the jaws].

Bisphosphonates (BPs), as potent drugs inhibiting bone resorption, have been widely used for treatment of several diseases. In recent years, dentists and oral and maxillofacial surgeons reported continuously increasing cases of bisphosphonate-related osteonecrosis of the jaws (BRONJ). This disease is clinically characterized by exposed bones, formation of sequestrum, pain, and halitosis. Provided that pathogenesis of BRONJ is unclear, effective treatments for this disease are currently unavailable. Thus, prevention plays an important role in the management of BRONJ. This review summarizes research progress on pathogenesis, risk factors, clinical characteristics, treatment, and prevention of this condition.

[Cone beam computed tomography evaluation of bifid mandibular canals in the adult population in Sichuan Province].

OBJECTIVE: To investigate the incidence of bifid mandibular canals (BMC), and analyze the types, courses, and anatomic features of the variant canals in the adult population in Sichuan Province. METHODS: Five hundred patients (1 000 hemimandibles) underwent cone beam computed tomography (CBCT) were included in this study. The incidence, bifurcate types and courses of the BMC were evaluated. RESULTS: The incidence of BMC was 13.8% (69/500) in the study, 9.2% in terms of total hemimandibles. The most frequently type was retromolar canals, followed by the dental and buccolingual type, meanwhile the lowest was the forward type. The mean diameter of the accessory canals was 0.90 mm and the mean length was 9.39 mm. CONCLUSIONS: CBCT used in this study has shown that the incidence of BMC assessed by CBCT was significantly higher than panoramic radiography. Furthermore, CBCT can depict the position, course, size and the branches of the mandibular canals.
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SENP1 regulates cell migration and invasion in neuroblastoma.

Neuroblastoma (NB) is an embryonic solid tumor derived from precursor cells of the sympathetic nervous system, and accounts for 11% of childhood cancers and around 15% of cancer deaths in children. SUMOylation and deSUMOylation are dynamic mechanisms regulating a spectrum of protein activities. The SUMO proteases (SENP) remove SUMO conjugate from proteins, and their expression is deregulated in diverse cancers. However, nothing is known about the role of SENPs in NBL. In the present study, we found that SENP1 expression was significantly high in metastatic NB tissues compared with primary NB tissues. Overexpression of SENP1 promoted NB cells migration and invasion. Inhibition of SENP1 could significantly suppress NB cell migration and invasion. Moreover, we found that SENP1 could regulate the expression of CDH1, MMP9, and MMP2. In summary, the data presented here indicate a significant role of SENP1 in the regulation of cell migration and invasion in NB and suppress SENP1 expression as promising candidates for novel treatment strategies of NB.

[Exploratory study on influence of biopsy to biological behavior of Tca8113 transplanted tumor].

OBJECTIVE: We established an animal model of nude mice with Tca8113 tumor and cut some tissue for biopsy. We also determined the biological behavior and mechanisms of the tumor. METHODS: The mice were divided into two groups randomly. Mice in both groups were injected with Tca8113 cells into their tongues. The survival condition, growth of primary focus, and metastasis were observed. Hematoxylin and eosin staining and immunohistochemistry were performed on nuclear factor κB (NF-κB), matrix metallopeptidase 9 (MMP-9), vascular endothelial growth factor (VEGF), stromal cell-derived factor 1 (SDF-1), and Ki67 to determine their distributions within the tumor. Cytokeratin staining was also performed to detect micrometastasis in the submandibular lymph nodes. RESULTS: The emerging rate of tumor was 97.92%. The weight and survival time of the experimental group were lower than that of the control group, whereas the metastasis ratio was higher. The expression of NF-κB, MMP-9, SDF-1, and MMP-9 in tumors was higher in the experimental group than that in the control group. The expression of NF-κB, MMP-9, VEGF, and SDF-1 was relevant. The microvessel density of the experimental group was higher than that in the control group. CONCLUSIONS: Biopsy can affect the biological behavior of tongue tumor and can promote growth of primary focus and metastasis.

Molecular Mechanism of the Cell Death Induced by the Histone Deacetylase Pan Inhibitor LBH589 (Panobinostat) in Wilms Tumor Cells.

BACKGROUND: Wilms tumor (WT) is an embryonic kidney cancer, for which histone acetylation might be a therapeutic target. LBH589, a novel targeted agent, suppresses histone deacetylases in many tumors. This study investigated the antitumor activity of LBH589 in SK-NEP-1 and G401 cells. METHODS: SK-NEP-1 and G401 cell growth was assessed by CCK-8 and in nude mice experiments. Annexin V/propidium iodide staining followed by flow cytometry detected apoptosis in cell culture. Gene expressions of LBH589-treated tumor cells were analyzed using an Arraystar Human LncRNA Array. The Multi Experiment View cluster software analyzed the expression data. Differentially expressed genes from the cluster analyses were imported into the Ingenuity Pathway Analysis tool. RESULTS: LBH589 inhibited cell proliferation of SK-NEP-1 and G401 cells in a dose-dependent manner. Annexin V, TUNEL and Hochest 33342 staining analysis showed that LBH589-treated cells showed more apoptotic features compared with the control. LBH589 treatment inhibited the growth of SK-NEP-1 xenograft tumors in nude mice. Arraystar Human LncRNA Array analysis of genes and lncRNAs regulated by LBH589 identified 6653 mRNAs and 8135 lncRNAs in LBH589-treated SK-NEP-1 cells. The most enriched gene ontology terms were those involved in nucleosome assembly. KEGG pathway analysis identified cell cycle proteins, including CCNA2, CCNB2, CCND1, CCND2, CDK4, CDKN1B and HDAC2, etc. Ingenuity Pathway Analysis identified important upstream molecules: HIST2H3C, HIST1H4A, HIST1A, HIST1C, HIST1D, histone H1, histone H3, RPRM, HSP70 and MYC. CONCLUSIONS: LBH589 treatment caused apoptosis and inhibition of cell proliferation of SK-NEP-1and G401 cells. LBH589 had a significant effect and few side effects on SK-NEP-1 xenograft tumors. Expression profiling, and GO, KEGG and IPA analyses identified new targets and a new "network" of genes responding to LBH589 treatment in SK-NEP-1 cells. RPRM, HSP70 and MYC may be important regulators during LBH589 treatment. Our results provide new clues to the proapoptotic mechanism of LBH589.

Combined hand gesture--speech model for human action recognition.

This study proposes a dynamic hand gesture detection technology to effectively detect dynamic hand gesture areas, and a hand gesture recognition technology to improve the dynamic hand gesture recognition rate. Meanwhile, the corresponding relationship between state sequences in hand gesture and speech models is considered by integrating speech recognition technology with a multimodal model, thus improving the accuracy of human behavior recognition. The experimental results proved that the proposed method can effectively improve human behavior recognition accuracy and the feasibility of system applications. Experimental results verified that the multimodal gesture-speech model provided superior accuracy when compared to the single modal versions.

The promoter of miR-663 is hypermethylated in Chinese pediatric acute myeloid leukemia (AML).

BACKGROUND: There is growing evidence supporting a role for microRNAs (miRNA) as targets in aberrant mechanisms of DNA hypermethylation. Epigenetic silencing of tumor suppressor miRNAs, including miR-663, which has recently been reported to be inactivated by hypermethylation in several cancers, may play important roles in pediatric acute myeloid leukemia (AML). However, expression of miR-663 and its promoter methylation remain status unclear in childhood leukemia. METHODS: Promoter methylation status of miR-663 was investigated by methylation specific PCR (MSP) and bisulfate genomic sequencing (BGS). Transcriptional expression of miR-663 was evaluated by semi-quantitative and real-time PCR, and the relationship between expression of miR-663 and promoter methylation was confirmed using 5-aza-2'-deoxycytidine (5-Aza) demethylation reagent. RESULTS: MiR-663 was aberrantly methylated in 45.5% (5/11) leukemia cell lines; BGS showed that the promoter was significantly methylated in three AML cell lines; methylation of miR-663 was significantly higher in Chinese pediatric AML patients [41.4% (29/70)] compared to normal bone marrow (NBM) control samples [10.0% (3/30)]. These results were confirmed by both BGS and 5-Aza demethylation analysis. In addition, miR-663 transcript expression was significantly lower in AML patients, both with and without miR-663 methylation, compared to controls; however, there were no significant differences in clinical features or French-American-British (FAB) classification between patients with and without miR-663 methylation. CONCLUSIONS: Expression of miR-663 was significantly lower in pediatric AML cells compared to NBM controls; furthermore, a high frequency of miR-663 promoter hypermethylation was observed in both AML cell lines and pediatric AML samples. Inactivation of miR-663 by promoter hypermethylation could be affected by 5-Aza demethylation. These findings suggest that hypermethylation of the miR-663 promoter may be an early event in the development of pediatric AML.

Inhibition of the ecto-beta subunit of F1F0-ATPase inhibits proliferation and induces apoptosis in acute myeloid leukemia cell lines.

BACKGROUND: Leukemia, a heterogeneous clonal disorder of hematopoietic progenitor cells, presents a world-wide health problem, especially in childhood. F1F0 ATPase, an inner mitochondrial enzyme, is expressed on the plasma membrane of tumor cells, and its inhibition induces both anti-angiogenic and anti-tumorigenic activity. METHODS: Monoclonal Antibody (McAb) against ATPase was produced by polyethylene glycol-mediated fusions and screened by ELISA. Proliferation, cell cycle and apoptosis of cells were analyzed when the surface ATPase of cells was blockaded with McAb. RESULTS: We detected cell-membrane expression of the F1F0 ATPase ß subunit on 0.1% to 56% of the 11 cell lines derived from leukemia, including acute myeloid leukemia (AML). We produced a monoclonal antibody, McAb7E10, which recognizes both the native and recombinant ATPase ß subunit, with a dissociation constant (KD) of 3.26E-10. We demonstrate that McAb7E10 binds to ATPase at the cell surface, where it is able to inhibit ATP synthesis. McAb7E10 significantly inhibited proliferation of AML cell lines in vitro: the relative inhibitory rates of 50 µg/mL McAb7E10 treated MV4-11and HL-60 cells were 69.6% and 81.9% respectively. Cell cycle analysis indicated that McAb7E10 significantly induced apoptosis in MV4-11 and HL-60 cells: the relative rates of apoptosis in 5, 10 and 50ug/mL McAb7E10 treated MV4-11 cells was 3.6 ± 0.83%, 8.4 ± 1.69% and 17.3 ± 2.56% compared to 1.5% ± 0.85% in mouse IgG treated cells (p < 0.01). The relative rate of apoptosis in 5, 10 and 50ug/mL McAb7E10 treated HL-60 cells was 5.5 ± 2.37%, 11.3 ± 3.62% and 19.9 ± 3.31% compared to 1.56% ± 0.97% in mouse IgG treated cells (p < 0.01). Annexin V staining demonstrated that the relative apoptotic rates in 50 µg/mL McAb7E10 treated MV4-11 and HL-60 cells were 50.5% ± 7.04% and 32.9% ± 4.52%, respectively, significantly higher than IgG control antibody treated cells were 21.9% ± 3.11% and 15.3% ± 3.95%, p < 0.01. CONCLUSIONS: These findings indicate that ectopic expression of ATPase ß subunit may be a tumor-associated antigen in hematological malignancies. The F1F0 ATPase ß subunit provides a potential target for immunotherapy in AML and hematological malignancies.

Analyzing the gene expression profile of pediatric acute myeloid leukemia with real-time PCR arrays.

BACKGROUND: The Real-time PCR Array System is the ideal tool for analyzing the expression of a focused panel of genes. In this study, we will analyze the gene expression profile of pediatric acute myeloid leukemia with real-time PCR arrays. METHODS: Real-time PCR array was designed and tested firstly. Then gene expression profile of 11 pediatric AML and 10 normal controls was analyzed with real-time PCR arrays. We analyzed the expression data with MEV (Multi Experiment View) cluster software. Datasets representing genes with altered expression profile derived from cluster analyses were imported into the Ingenuity Pathway Analysis Tool. RESULTS: We designed and tested 88 real-time PCR primer pairs for a quantitative gene expression analysis of key genes involved in pediatric AML. The gene expression profile of pediatric AML is significantly different from normal control; there are 19 genes up-regulated and 25 genes down-regulated in pediatric AML. To investigate possible biological interactions of differently regulated genes, datasets representing genes with altered expression profile were imported into the Ingenuity Pathway Analysis Tool. The results revealed 12 significant networks. Of these networks, Cellular Development, Cellular Growth and Proliferation, Tumor Morphology was the highest rated network with 36 focus molecules and the significance score of 41. The IPA analysis also groups the differentially expressed genes into biological mechanisms that are related to hematological disease, cell death, cell growth and hematological system development. In the top canonical pathways, p53 and Huntington's disease signaling came out to be the top two most significant pathways with a p value of 1.5E-8 and2.95E-7, respectively. CONCLUSIONS: The present study demonstrates the gene expression profile of pediatric AML is significantly different from normal control; there are 19 genes up-regulated and 25 genes down-regulated in pediatric AML. We found some genes dyes-regulated in pediatric AML for the first time as FASLG, HDAC4, HDAC7 and some HOX family genes. IPA analysis showed the top important pathways for pediatric AML are p53 and Huntington's disease signaling. This work may provide new clues of molecular mechanism in pediatric AML.

Promoter of TFPI-2 is hypermethylated in Chinese pediatric acute myeloid leukemia.

Human tissue factor pathway inhibitor-2 (TFPI-2) has been implicated as a metastasis-associated gene in many types of tumors. In this study, we investigated whether TFPI-2 was inactivated epigenetically in pediatric acute myeloid leukemia (AML). Methylation status was investigated by methylation-specific polymerase chain reaction and bisulfate genomic sequencing. TFPI-2 was aberrantly methylated in 50% (3/6) of AML cell lines. Aberrant methylation of TFPI-2 promoter was detected in 71.6% (48/67) of the Chinese pediatric AML patients. TFPI-2 transcript was significantly lower in AML group compared with controls (3.44 vs. 32.8, P<0.001). Patients with methylated TFPI-2 gene had significantly lower TFPI-2 transcript than those patients without methylated TFPI-2 (P=0.04). Promoter hypermethylation of TFPI-2 is frequent and specific event in pediatric AML.

MMP28 (epilysin) as a novel promoter of invasion and metastasis in gastric cancer.

BACKGROUND: The purpose of this study was to investigate invasion and metastasis related genes in gastric cancer. METHODS: The transwell migration assay was used to select a highly invasive sub-line from minimally invasive parent gastric cancer cells, and gene expression was compared using a microarray. MMP28 upregulation was confirmed using qRT-PCR. MMP28 immunohistochemistry was performed in normal and gastric cancer specimens. Invasiveness and tumor formation of stable cells overexpressing MMP28 were tested in vitro and in vivo. RESULTS: MMP28 was overexpressed in the highly invasive sub-cell line. Immunohistochemistry revealed MMP28 expression was markedly increased in gastric carcinoma relative to normal epithelia, and was significantly associated with depth of tumor invasion, lymph node metastasis and poorer overall survival. Ectopic expression of MMP28 indicated MMP28 promoted tumor cell invasion in vitro and increased gastric carcinoma metastasis in vivo. CONCLUSIONS: This study indicates MMP28 is frequently overexpressed during progression of gastric carcinoma, and contributes to tumor cell invasion and metastasis. MMP28 may be a novel therapeutic target for prevention and treatment of metastases in gastric cancer.

Retinoic acid induces HL-60 cell differentiation via the upregulation of miR-663.

BACKGROUND: Differentiation of the acute myeloid leukemia (AML) cell line HL-60 can be induced by all trans-retinoic acid (ATRA); however, the mechanism regulating this process has not been fully characterized. METHODS: Using bioinformatics and in vitro experiments, we identified the microRNA gene expression profile of HL-60 cells during ATRA induced granulocytic differentiation. RESULTS: Six microRNAs were upregulated by ATRA treatment, miR-663, miR-494, miR-145, miR-22, miR-363* and miR-223; and three microRNAs were downregulated, miR-10a, miR-181 and miR-612. Additionally, miR-663 expression was regulated by ATRA. We used a lentivirus (LV) backbone incorporating the spleen focus forming virus (SFFV-F) promoter to drive miR-663 expression, as the CMV (Cytomegalovirus) promoter is ineffective in some lymphocyte cells. Transfection of LV-miR-663 induced significant HL-60 cell differentiation in vitro. CONCLUSIONS: Our results show miR-663 may play an important role in ATRA induced HL-60 cell differentiation. Lentivirus delivery of miR-663 could potentially be used directly as an anticancer treatment in hematological malignancies.

Altered phenotype of lymphatic endothelial cells induced by highly metastatic OTSCC cells contributed to the lymphatic metastasis of OTSCC cells.

The lymphatic endothelial cell (LEC) is an interactive surface for cancer cells. This article aims to explore cancer cell-induced changes of LEC, and study the tumor-lymphatic endothelium interaction. Here, LECs were co-cultured with highly and poorly metastatic tongue cancer cells. The differences in biologic behaviors and gene expression profiles between them were examined. The results showed that LECs induced by highly metastatic cancer cells displayed abnormal biologic behaviors, and could secrete chemokines to promote the migration of cancer cells. Therefore, biologic properties and functional status of LECs in oral tongue squamous cell carcinoma (OTSCC) might be a positive factor in lymphatic dissemination.

Oral cancer cells with different potential of lymphatic metastasis displayed distinct biologic behaviors and gene expression profiles.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) often spreads from the primary tumor to regional lymph nodes in the early stage. Better understanding of the biology of lymphatic spread of oral cancer cells is important for improving the survival rate of cancer patients. METHODS: We established the cell line LNMTca8113 by repeated injections in foot pads of nude mice, which had a much higher lymphatic metastasis rate than its parental cell line Tca8113. Then, we compared the biologic behaviors of cancer cells between them. Moreover, microarray-based expression profiles between them were also compared, and a panel of differential genes was validated using real-time-PCR. RESULTS: In contrast to Tca8113 cells, LNMTca8113 cells were more proliferative and resistant to apoptosis in the absence of serum, and had enhanced ability of inducing capillary-like structures. Moreover, microarray-based expression profiles between them identified 1341 genes involved in cell cycle, cell adhesion, lymphangiogenesis, regulation of apoptosis, and so on. Some genes dedicating to the metastatic potential, including JAM2, TNC, CTSC, LAMB1, VEGFC, HAPLN1, ACPP, GDF9 and FGF11, were upregulated in LNMTca8113 cells. CONCLUSION: These results suggested that LNMTca8113 and Tca8113 cells were proper models for lymphatic metastasis study because there were differences in biologic behaviors and metastasis-related genes between them. Additionally, the differentially expressed gene profiles in cancer progression may be helpful in exploring therapeutic targets and provide the foundation for further functional validation of these specific candidate genes for OSCC.

Identification of oral cancer cell-induced changes in gene expression profile of lymphatic endothelial cell.

Understading functional properties of tumor-derived lymphatic endothelial cells (TLEC) are relevant for blocking lymphatic metastasis. The changes of lymphatic endothelial cells (LEC) cocultured with oral cancer cells in a vitro model were examined. TLEC, in contrast to LEC, were more proliferative and have enhanced ability of lymphangiogenesis and anti-apoptosis. Gene microarrays revealed that 677 unique genes had two-fold or higher change between the two groups. Differential expressions of selected genes were confirmed by real-time PCR. Our results indicate that TLEC display abnormal characteristics and are distinct at the molecular level. Manipulation of TLEC is encouraging for therapy of lymphatic metastasis.