CiteULike: carmenv's cancer

Eph-ephrin signalling in adult tissues and cancer.

A Merlos-Suárez — 2008-05-15T16:56:36-00:00

Current opinion in cell biology, Vol. 20, No. 2. (April 2008), pp. 194-200.

Eph receptor tyrosine kinases and their ligands, the ephrins, play key roles in the regulation of migration and cell adhesion during development, thereby influencing cell fate, morphogenesis and organogenesis. Recent findings suggest that Eph signalling also controls the architecture and physiology of different tissues in the adult body under normal and pathological conditions such as cancer. A prime example is the intestinal epithelium where EphB-ephrinB interactions regulate both cell positioning and tumor progression. Here, we will review recent advances on the role of Eph-ephrin signalling in the intestine and other organs.

Expression of microRNAs and protein-coding genes associated with perineural invasion in prostate cancer.

Robyn L Prueitt — 2008-05-14T23:34:41-00:00

The Prostate (5 May 2008)

BACKGROUND: Perineural invasion (PNI) is the dominant pathway for local invasion in prostate cancer. To date, only few studies have investigated the molecular differences between prostate tumors with PNI and those without it. METHODS: To evaluate the involvement of both microRNAs and protein-coding genes in PNI, we determined their genome-wide expression with a custom microRNA microarray and Affymetrix GeneChips in 50 prostate adenocarcinomas with PNI and 7 without it. In situ hybridization (ISH) and immunohistochemistry was used to validate candidate genes. RESULTS: Unsupervised classification of the 57 adenocarcinomas revealed two clusters of tumors with distinct global microRNA expression. One cluster contained all non-PNI tumors and a subgroup of PNI tumors. Significance analysis of microarray data yielded a list of microRNAs associated with PNI. At a false discovery rate (FDR) <10%, 19 microRNAs were higher expressed in PNI tumors than in non-PNI tumors. The most differently expressed microRNA was miR-224. ISH showed that this microRNA is expressed by perineural cancer cells. The analysis of protein-coding genes identified 34 transcripts that were differently expressed by PNI status (FDR < 10%). These transcripts were down-regulated in PNI tumors. Many of those encoded metallothioneins and proteins with mitochondrial localization and involvement in cell metabolism. Consistent with the microarray data, perineural cancer cells tended to have lower metallothionein expression by immunohistochemistry than nonperineural cancer cells. CONCLUSIONS: Although preliminary, our findings suggest that alterations in microRNA expression, mitochondrial function, and cell metabolism occur at the transition from a noninvasive prostate tumor to a tumor with PNI. Prostate Published 2008 Wiley-Liss, Inc.

Cancerous miRNAs and their regulation.

Xu-Bao Shi — 2008-05-14T23:32:18-00:00

Cell cycle (Georgetown, Tex.), Vol. 7, No. 11. (19 March 2008)

Although they account for only a very minor fraction of the expressed genome, microRNAs (miRNAs) are pivotal regulators of development and cellular homeostasis through their control of diverse cellular processes including proliferation, differentiation, apoptosis, survival, motility, and morphogenesis. Accordingly, several miRNAs have been functionally classified as proto-oncogenes or tumor suppressors and are aberrantly expressed in different cancer types. Deregulation (e.g., overexpression or loss of expression) of these so-called "cancerous" miRNAs can figure prominently in tumor initiation and progression by elaborating an inappropriate cellular program promoting uncontrolled proliferation, favoring survival, inhibiting differentiation, and/or promoting invasive behavior. These features would certainly promote tumor dissemination and persistence by favoring metastasis and therapy resistance. Cancerous miRNAs therefore represent attractive molecules for exploitation as biomarkers and therapeutic targets. In this review, we highlight recently characterized cancerous miRNAs and the mechanisms through which they contribute to the pathogenesis of human cancers. We also discuss the signal transduction pathways that regulate the expression of these miRNAs with particular attention to several essential transcription factors such as Myc, p53, and the androgen receptor.

Vimentin affects the mobility and invasiveness of prostate cancer cells.

Yan Zhao — 2008-05-12T22:19:57-00:00

Cell biochemistry and function (8 May 2008)

A significant proportion of prostate cancer patients treated with curative intent go on to develop advanced disease. At a fundamental biological level, very little is known about what makes the disease aggressive and metastatic. Observational pathology reports and experimental data suggest that epithelial-mesenchymal transition is involved in prostate cancer invasiveness. Here, we investigated vimentin expression of prostate cancer cells, and explored the potential mechanism of vimentin promoting prostate cancer cells invasion. Vimentin expression was not detected in well differentiated tumors or in moderately differentiated tumors, but the majority of poorly differentiated cancers (5/11 with negative bone scan, 11/14 bone with positive scan) and bone metastases (8/8) had high vimentin expression in tumor cells. Downregulation of vimentin expression in PC-3 cells by transfection with antisense-vimentin led to a significant decrease in tumor cells motility and invasive activity. Furthermore, the expression of E-cadherin was inversely associated with expression of vimentin. Our results suggest that vimentin affects prostate cancer cells motility and invasiveness. Copyright (c) 2008 John Wiley & Sons, Ltd.

Anti-cancer and anti-angiogenic effects of curcumin and tetrahydrocurcumin on implanted hepatocellular carcinoma in nude mice.

P Yoysungnoen — 2008-04-29T16:19:40-00:00

World journal of gastroenterology : WJG, Vol. 14, No. 13. (7 April 2008), pp. 2003-2009.

AIM: To determine the effect of tetrahydrocurcumin (THC) on tumor angiogenesis compared with curcumin (CUR) by using both in vitro and in vivo models of human hepatocellular carcinoma cell line (HepG2). METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was used for testing the anti-proliferating activities of CUR and THC. In male BALB/c nude mice, 2 multiply 10(6) human HepG2 cells were inoculated onto a dorsal skin-fold chamber. One day after HepG2 inoculation, the experimental groups were fed oral daily with CUR or THC (300 mg/kg or 3000 mg/kg). On d 7, 14 and 21, the tumor microvasculature was observed using fluorescence videomicroscopy and capillary vascularity (CV) was measured. RESULTS: Pathological angiogenic features including microvascular dilatation, tortuosity, and hyper-permeability were observed. CUR and THC could attenuate these pathologic features. In HepG2-groups, the CV were significantly increased on d 7 (52.43%), 14 (69.17%), and 21 (74.08%), as compared to controls (33.04%, P < 0.001). Treatment with CUR and THC resulted in significant decrease in the CV (P < 0.005 and P < 0.001, respectively). In particular, the anti-angiogenic effects of CUR and THC were dose-dependent manner. However, the beneficial effect of THC treatment than CUR was observed, in particular, from the 21 d CV (44.96% and 52.86%, P < 0.05). CONCLUSION: THC expressed its anti-angiogenesis without any cytotoxic activities to HepG2 cells even at the highest doses. It is suggested that anti-angiogenic properties of CUR and THC represent a common potential mechanism for their anti-cancer actions.

Curcumin inhibits WEHI-3 leukemia cells in BALB/c mice in vivo.

CC Su — 2008-04-29T16:18:45-00:00

In vivo (Athens, Greece), Vol. 22, No. 1. (b 2008), pp. 63-68.

Curcumin (1, 7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5- dione), a natural polyphenol product of the plant Curcuma longa, exhibited potent inhibitory activities against proliferation, induced cell cycle arrest and exhibited the induction of apoptosis in several tumor cell lines. In our previous studies, we have shown that curcumin induced cell cycle arrest and apoptosis on human leukemia HL-60 and mouse leukemia WEHI-3 cells; there are no reports regarding whether or not it affects leukemia cells in vivo. In the present study, we investigated the effects of curcumin on WEHI-3 in BALB/c mice and the results indicated that curcumin reduces the percentage of Mac-3 marker, which is the precursor of macrophage. Curcumin induced significant effects on the population of B cells from murine leukemia in vivo. We also investigated the weights of spleen and liver from murine leukemia and the results showed that curcumin reduced the weight of the liver and spleen. From the pathological examinations, the effects of curcumin on the liver and spleen from mice after being injected with WEHI-3 cells were apparent. Both organs were enlarged. In conclusion, curcumin affect WEHI-3 cells in vivo.

Evaluation of a nanotechnology-based carrier for delivery of curcumin in prostate cancer cells.

RL Thangapazham — 2008-04-29T16:07:45-00:00

International journal of oncology, Vol. 32, No. 5. (May 2008), pp. 1119-1123.

We have initiated studies to enhance targeted delivery of an anticancer agent, curcumin, for prostate cancer treatment by incorporating this agent into the liposomes (nanodelivery vehicles primarily composed of phospholipids) coated with prostate membrane specific antigen specific antibodies. We prepared curcumin-loaded liposomes of various lipid compositions by sonication at an average size of 100-150 nm. Un-entrapped curcumin was removed by size exclusion chromatography. Data show that curcumin preferentially partitioned into liposomes prepared from dimyristoyl phosphatidyl choline (DMPC) and cholesterol among the various compositions tested. The anti-proliferative activity of liposomal curcumin was studied using two human prostate cancer cell lines (LNCaP and C4-2B) by a tetrazolium dye-based (MTT) assay. Treatment of cells with liposomal curcumin (5-10 microM) for 24-48 h at 37 degrees C resulted in at least 70-80% inhibition of cellular proliferation without affecting their viability. On the other hand, free curcumin exhibited similar inhibition only at 10-fold higher doses (>50 microM). We also observed that LNCaP cells were relatively more sensitive to liposomal curcumin mediated block of cellular proliferation than C4-2B cells. We are currently developing liposome formulations with targeting ability to further improve the efficacy of curcumin in vivo.

Curcuma drugs and curcumin regulate the expression and function of P-gp in Caco-2 cells in completely opposite ways.

Xiao-Long Hou — 2008-04-29T16:04:01-00:00

International journal of pharmaceutics (18 March 2008)

Curcumin is a phenolic compound isolated from rhizomes of C. longa, C. aromatica and other Curcumas except C. zedoaria. Recently, both curcumin and Curcumas have become prevalent as supplement. P-gp has been reported as an important determinant for drug absorption in small intestine. In this study, Caco-2 cell monolayers were treated with methanol extracts of Curcumas (0.1mg/ml) or curcumin (30muM) for 72h to investigate the relationship between the potential affects of Curcumas and curcumin on P-gp. [(3)H]-digoxin and rhodamine 123 were used to evaluate P-gp activity. All Curcumas significantly increased the activity of P-gp by up-regulating the expressions of P-gp protein and MDR1 mRNA levels. Interestingly, contrary to Curcumas, curcumin treatment inhibited the activity of P-gp with a decrease in P-gp protein and MDR1 mRNA expression levels. Curcumas might alter the pharmacokinetics of co-administrated drugs by up-regulating the function and expression levels of intestinal P-gp. However, curcumin has no relationship with the inductive effect of Curcumas since curcumin showed an opposite effects. Caution should be exercised when Curcumas or curcumin are to be consumed with drugs that are P-gp substrates because Curcumas and curcumin might regulate the function of P-gp in completely opposite ways.