A nanocomplex that is both tumor cell-selective and cancer gene-specific for anaplastic large cell lymphoma

Background  

Many in vitro studies have demonstrated that silencing of cancerous genes by siRNAs is a potential therapeutic approach for blocking tumor growth. However, siRNAs are not cell type-selective, cannot specifically target tumor cells, and therefore have limited in vivo application for siRNA-mediated gene therapy.     

Glycosaminoglycans modulate C6 glioma cell adhesion to extracellular matrix components and alter cell proliferation and cell migration

Background  

Adhesion to extracellular matrix (ECM) components has been implicated in the proliferative and invasive properties of tumor cells. We investigated the ability of C6 glioma cells to attach to ECM components in vitro and described the regulatory role of glycosaminoglycans (GAGs) on their adhesion to the substrate, proliferation and migration.     

An <Emphasis Type="Italic">in vivo</Emphasis> RNA interference screen identifies gene networks controlling <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>blood cell homeostasis

Background  

In metazoans, the hematopoietic system plays a key role both in normal development and in defense of the organism. In Drosophila, the cellular immune response involves three types of blood cells: plasmatocytes, crystal cells and lamellocytes. This last cell type is barely present in healthy larvae, but its production is strongly induced upon wasp parasitization or in mutant contexts affecting larval blood cell homeostasis. Notably, several zygotic mutations leading to melanotic mass (or "tumor") formation in larvae have been associated to the deregulated differentiation of lamellocytes. To gain further insights into the gene regulatory network and the mechanisms controlling larval blood cell homeostasis, we conducted a tissue-specific loss of function screen using hemocyte-specific Gal4 drivers and UAS-dsRNA transgenic lines.     

Multiple homoplasious insertions and deletions of a Triticeae (Poaceae) DNA transposon: a phylogenetic perspective

Background  

Stowaway elements are short, non-autonomous DNA transposons categorized as miniature inverted-repeat transposable elements (MITEs). The high MITE copy number in grass genomes suggests an active history of amplification and insertion, but ongoing MITE activity has only rarely been seen, and ongoing Stowaway activity has never been observed. Thus, a phylogenetic perspective on presence vs. absence of elements in an aligned data set can provide valuable historical insights into the dynamics of MITE acquisition and loss.     

Modulation of redox homeostasis under suboptimal conditions by Arabidopsis nudix hydrolase 7

Background  

Nudix hydrolases play a key role in maintaining cellular homeostasis by hydrolyzing various nuceloside diphosphate derivatives and capped mRNAs. Several independent studies have demonstrated that Arabidopsis nudix hydrolase 7 (AtNUDT7) hydrolyzes NADH and ADP-ribose. Loss of function Atnudt7-1 mutant plants (SALK_046441) exhibit stunted growth, higher levels of reactive oxygen species, enhanced resistance to pathogens. However, using the same T-DNA line, two other groups reported that mutant plants do not exhibit any visible phenotypes. In this study we analyze plausible factors that account for differences in the observed phenotypes in Atnudt7. Secondly, we evaluate the biochemical and molecular consequences of increased NADH levels due to loss of function of AtNUDT7 in Arabidopsis.     

INTS6/DICE1 inhibits growth of human androgen-independent prostate cancer cells by altering the cell cycle profile and Wnt signaling

Background  

The gene encoding integrator complex subunit 6 (INTS6), previously known as deleted in cancer cells 1 (DICE1, OMIM 604331) was found to be frequently affected by allelic deletion and promoter hypermethylation in prostate cancer specimens and cell lines. A missense mutation has been detected in prostate cancer cell line LNCaP. Together, these results suggest INTS6/DICE1 as a putative tumor suppressor gene in prostate cancer. In this study, we examined the growth inhibitory effects of INTS6/DICE1 on prostate cancer cells.     

<Emphasis Type="Italic">Dppa3 / Pgc7 / stella</Emphasis> is a maternal factor and is not required for germ cell specification in mice

Background  

In mice, germ cells are specified through signalling between layers of cells comprising the primitive embryo. The function of Dppa3 (also known as Pgc7 or stella), a gene expressed in primordial germ cells at the time of their emergence in gastrulating embryos, is unknown, but a recent study has claimed that it plays a central role in germ cell specification.     

A natural compound from <Emphasis Type="Italic">Hydnophytum formicarium</Emphasis> induces apoptosis of MCF-7 cells via up-regulation of Bax

Background  

Hydnophytum formicarium Jack is an epyphytic shrub that belongs to the family of Rubiaceae and is native to the tropical rain forests of the Asean region, which includes Malaysia. A flavanoid derivative, 7, 3', 5'-trihydroxyflavanone (3HFD), isolated from H. formicarium has been reported to have cytotoxic effects on the human breast carcinoma cell line MCF-7. The aim of the current study was to investigate the mode of cell death in MCF-7 cells treated with 3HFD. A DNA fragmentation assay was conducted on isolated genomic DNA, a TUNEL assay was used to determine the mode of cell death and Western blotting was used to evaluate the expression levels of Bax and Bcl-2. Immunofluorescence staining of MCF-7 cells was also performed to confirm the up-regulation of the Bax protein.     

Late stage inhibition of hematogenous melanoma metastasis by cystatin C over-expression

Background  

Tumor metastasis is a frequent cause of treatment failure for cancer patients. A key feature of metastatic cancer cells is their invasive ability. Cysteine proteases contribute to invasive properties of many cancer cell types. To analyze the contribution of cysteine proteases to metastasis we have over-expressed in B16 melanoma cells the natural cysteine protease inhibitor, cystatin C. We measured in vitro invasion of cystatin over-expression clones with Boyden chamber type assays. Tail-vein injections of cells were used to compare lung tumor colonization. Subcutaneous tumor growth and tumor cell metastasis from primary tumors were also analyzed. Apoptosis of tumor cells was measured in lung tissues following melanoma cell injection.     

Role of Scrib and Dlg in anterior-posterior patterning of the follicular epithelium during Drosophila oogenesis

Background  

Proper patterning of the follicle cell epithelium over the egg chamber is essential for the Drosophila egg development. Differentiation of the epithelium into several distinct cell types along the anterior-posterior axis requires coordinated activities of multiple signaling pathways. Previously, we reported that lethal(2)giant larvae (lgl), a Drosophila tumor suppressor gene, is required in the follicle cells for the posterior follicle cell (PFC) fate induction at mid-oogenesis. Here we explore the role of another two tumor suppressor genes, scribble (scrib) and discs large (dlg), in the epithelial patterning.     

Enhanced phenol degradation by immobilized Acinetobacter sp. strain AQ5NOL 1

A locally isolated Acinetobacter sp. Strain AQ5NOL 1 was encapsulated in gellan gum and its ability to degrade phenol was compared with the free cells. Optimal phenol degradation was achieved at gellan gum concentration of 0.75% (w/v), bead size of 3 mm diameter (estimated surface area of 28.26 mm²) and bead number of 300 per 100 ml medium. At phenol concentration of 100 mg l⁻¹, both free and immobilized bacteria exhibited similar rates of phenol degradation but at higher phenol concentrations, the immobilized bacteria exhibited a higher rate of degradation of phenol. The immobilized cells completely degrade phenol within 108, 216 and 240 h at 1,100, 1,500 and 1,900 mg l⁻¹ phenol, respectively, whereas free cells took 240 h to completely degrade phenol at 1,100 mg l⁻¹. However, the free cells were unable to completely degrade phenol at higher concentrations. Overall, the rates of phenol degradation by both immobilized and free bacteria decreased gradually as the phenol concentration was increased. The immobilized cells showed no loss in phenol degrading activity after being used repeatedly for 45 cycles of 18 h cycle. However, phenol degrading activity of the immobilized bacteria experienced 10 and 38% losses after the 46 and 47th cycles, respectively. The study has shown an increased efficiency of phenol degradation when the cells are encapsulated in gellan gum.     

Hypothyroidism Enhances Tumor Invasiveness and Metastasis Development

Background

Whereas there is increasing evidence that loss of expression and/or function of the thyroid hormone receptors (TRs) could result in a selective advantage for tumor development, the relationship between thyroid hormone levels and human cancer is a controversial issue. It has been reported that hypothyroidism might be a possible risk factor for liver and breast cancer in humans, but a lower incidence of breast carcinoma has been also reported in hypothyroid patients

Methodology/Principal Findings

In this work we have analyzed the influence of hypothyroidism on tumor progression and metastasis development using xenografts of parental and TRβ1–expressing human hepatocarcinoma (SK-hep1) and breast cancer cells (MDA-MB-468). In agreement with our previous observations tumor invasiveness and metastasis formation was strongly repressed when TRβ–expressing cells were injected into euthyroid nude mice. Whereas tumor growth was retarded when cells were inoculated into hypothyroid hosts, tumors had a more mesenchymal phenotype, were more invasive and metastatic growth was enhanced. Increased aggressiveness and tumor growth retardation was also observed with parental cells that do not express TRs.

Conclusions/Significance

These results show that changes in the stromal cells secondary to host hypothyroidism can modulate tumor progression and metastatic growth independently of the presence of TRs on the tumor cells. On the other hand, the finding that hypothyroidism can affect differentially tumor growth and invasiveness can contribute to the explanation of the confounding reports on the influence of thyroidal status in human cancer.     

3D nuclear organization of telomeres in the Hodgkin cell lines U-HO1 and U-HO1-PTPN1: PTPN1 expression prevents the formation of very short telomeres including "t-stumps"

Background  

In cancer cells the three-dimensional (3D) telomere organization of interphase nuclei into a telomeric disk is heavily distorted and aggregates are found. In Hodgkin's lymphoma quantitative FISH (3D Q-FISH) reveals a major impact of nuclear telomere dynamics during the transition form mononuclear Hodgkin (H) to diagnostic multinuclear Reed-Sternberg (RS) cells. In vitro and in vivo formation of RS-cells is associated with the increase of very short telomeres including "t-stumps", telomere loss, telomeric aggregate formation and the generation of "ghost nuclei".     

Antiproliferative activity of chloroformic extract of Persian Shallot, Allium hirtifolium, on tumor cell lines

Allium hirtifolim (Persian Shallot) belongs to Allium genus (Alliaceae family). We investigated the in vitro effects of chloroformic extract of A. hirtifolium and its Allicin on the proliferation of HeLa (cervical cancer), MCF7 (human, caucasion, breast, adenocarcinoma) and L929 (mouse, C3H/An, connective) cell lines. Our results showed that components of A. hirtifolium might inhibit proliferation of tumor cell lines. This inhibition in HeLa and MCF-7 cells was dose-dependent. The presence of Allicin was evaluated by TLC method in bulbs and the extract of A. hirtifolium was analyzed by HPLC. MTT test was performed 24, 48 and 72 h after cell culture. A significant decrease in cell lines was observed in HeLa and MCF-7 as compared to L929 cell lines. DNA fragmentation analysis revealed a large number of apoptotic cells in treated HeLa and MCF-7 cell groups, but no effects in L929 cells. Therefore A. hirtifolium might be a candidate for tumor suppression.     

PETALS: Proteomic Evaluation and Topological Analysis of a mutated Locus' Signaling

Background  

Colon cancer is driven by mutations in a number of genes, the most notorious of which is Apc. Though much of Apc's signaling has been mechanistically identified over the years, it is not always clear which functions or interactions are operative in a particular tumor. This is confounded by the presence of mutations in a number of other putative cancer driver (CAN) genes, which often synergize with mutations in Apc.     

Transcriptional regulation of subclass 5b fimbriae

Background  

Enterotoxigenic Escherichia coli (ETEC) is a major cause of infant and child mortality in developing countries. This enteric pathogen causes profuse watery diarrhea by elaborating one or more enterotoxins that intoxicate eukaryotic cells and ultimately leads to a loss of water to the intestinal lumen. Virulence is also dependent upon fimbrial adhesins that facilitate colonization of the small intestine.     

Effects of extracellular DNA and DNA‐binding protein on the development of a Streptococcus intermedius biofilm

Aims

The aim of this study was to clarify the effects of homologous and heterologous extracellular DNAs (eDNAs) and histone‐like DNA‐binding protein (HLP) on Streptococcus intermedius biofilm development and rigidity.

Methods and Results

Formed biofilm mass was measured with 0·1% crystal violet staining method and observed with a scanning electron microscope. The localizations of eDNA and extracellular HLP (eHLP) in formed biofilm were detected by staining with 7‐hydoxyl‐9H‐(1,3‐dichloro‐9,9‐dimethylacridin‐2‐one) and anti‐HLP antibody without fixation, respectively. DNase I treatment (200 U ml^?1) markedly decreased biofilm formation and cell density in biofilms. Colocalization of eHLP and eDNA in biofilm was confirmed. The addition of eDNA (up to 1 μg ml^?1) purified from Strep. intermedius, other Gram‐positive bacteria, Gram‐negative bacteria, or human KB cells into the Strep. intermedius culture increased the biofilm mass of all tested strains of Strep. intermedius, wild‐type, HLP‐downregulated strain and control strains. In contrast, the addition of eDNA (>1 μg ml^?1) decreased the biofilm mass of all Strep. intermedius strains.

Conclusions

These findings demonstrated that eDNA and eHLP play crucial roles in biofilm development and its rigidity.

Significance and Impact of the Study

eDNA‐ and HLP‐targeting strategies may be applicable to novel treatments for bacterial biofilm‐related infectious diseases.     

Tooth loss and its relationship with protein intake by elderly Brazilians—A structural equation modelling approach

Objective

This study aimed at assessing the relationship between self‐perceived tooth loss and wearing dentures, on the one hand, and the consumption of protein, on the other hand, among the elderly population of Botucatu, SP. Food consumption tends to decrease with ageing, especially protein intake, and one of the causes could be the precariousness of oral health. Several risk factors associated with deficient dietary protein intake have been identified, namely greater physical dependence, reduced caloric intake and food insecurity, but no studies have analysed whether tooth loss and prostheses interfere with protein intake.

Methods

An interview was conducted among 365 elderly individuals, in which we examined oral health‐related quality of life (OHRQoL) as the only latent variable, in a 24‐hour nutritional assessment dietary recall repeated 3 times, conducted in person by a trained nutritionist and also performed an analysis of nutritional needs using the Nutrition Data System Research (NDSR) Program.

Results

The structural equation model, performed using Stata v.14, showed that lack of teeth (standardised coefficient [SC] = 0.21, P < .001), and prosthesis use (SC = ?0.21, P < .001) was associated with OHRQoL. Lack of teeth had a direct effect on the consumption of animal protein (SC = 0.08, P = .02), a strong total effect on animal protein intake (SC = 0.51, P = .04) and a medium effect on total protein intake (SC = 0.20, P = .03), adjusted for confounders (depression and medical problems).

Conclusion

Tooth loss had a strong and significant total effect on animal protein intake and a medium effect on total protein intake among elderly Brazilians.