Prognostic significance of fascin expression in advanced colorectal cancer: an immunohistochemical study of colorectal adenomas and adenocarcinomas

BACKGROUND: Fascin is an actin bundling protein with roles in the formation of cell protrusions and motility of mesenchymal and neuronal cells. Fascin is normally low or absent from epithelia, but is upregulated in several epithelial neoplasms where it may contribute to an invasive phenotype. Here, we report on the prevalence and potential clinical significance of fascin expression in relation to the progression of colorectal adenocarcinoma and to tumor cell proliferation as measured by Ki67 index. METHODS: Conventional tissue sections of 107 colorectal adenomas and 35 adenocarcinomas were analyzed by immunohistochemistry for fascin and Ki67 expression. Fascin expression and Ki67 proliferation index were also investigated by use of a tissue microarray containing cores from a further 158 colorectal adenocarcinomas and 15 adenomas linked to a CCF, IRB-approved database with a mean of 38 months of clinical follow-up. Survival analysis was carried out by the Kaplan-Meier and Cox regression methods. RESULTS: Fascin was not expressed by the normal colonic epithelium. In conventional sections, 16% of adenomas and 26% of adenocarcinomas showed fascin expression in greater than 10% of the tumor cells. In the clinically-annotated tumors, fascin immunoreactivity was more common in tumors located in the proximal colon (p = 0.009), but was not associated with age, gender, or TNM stage. Patients with stage III/IV adenocarcinomas (n = 62) with strong fascin immunoreactivity had a worse prognosis than patients with low or absent fascin, (3-year overall survival of 11% versus 43% for fascin-negative patients; p = 0.023). In adenomas, fascin and Ki67 tended to be inversely correlated at the cellular level; this trend was less apparent in adenocarcinomas. CONCLUSION: Fascin is upregulated in a proportion of adenomas, where its expression is often focal. Strong and diffuse expression was seen in a subset of advanced colorectal adenocarcinomas that correlated with shorter survival in stage III and IV patients. Fascin may have prognostic value as an early biomarker for more aggressive colorectal adenocarcinomas

Effects of small interfering RNAs targeting fascin on human esophageal squamous cell carcinoma cell lines

<p>Abstract</p> <p>Background</p> <p>Fascin induces membrane protrusions and cell motility. Fascin overexpression was associated with poor prognosis, and its downregulation reduces cell motility and invasiveness in esophageal squamous cell carcinoma (ESCC). Using a stable knockdown cell line, we revealed the effect of fascin on cell growth, cell adhesion and tumor formation.</p> <p>Methods</p> <p>We examined whether fascin is a potential target in ESCC using <it>in vitro </it>and <it>in vivo </it>studies utilizing a specific siRNA. We established a stable transfectant with downregulated fascin from KYSE170 cell line.</p> <p>Results</p> <p>The fascin downregulated cell lines showed a slower growth pattern by 40.3% (p < 0.01) and detachment from collagen-coated plates by 53.6% (p < 0.01), compared to mock cells, suggesting that fascin plays a role in cell growth by maintaining cell adhesion to the extracellular matrix. <it>In vivo</it>, the tumor size was significantly smaller in the tumor with fascin knockdown cells than in mock cells by 95% at 30 days after inoculation.</p> <p>Conclusions</p> <p>These findings suggest that fascin overexpression plays a role in tumor growth and progression in ESCC and that cell death caused by its downregulation might be induced by cell adhesion loss. This indicates that targeting fascin pathway could be a novel therapeutic strategy for the human ESCC.</p

Fascin overexpression promotes neoplastic progression in oral squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Fascin is a globular actin cross-linking protein, which plays a major role in forming parallel actin bundles in cell protrusions and is found to be associated with tumor cell invasion and metastasis in various type of cancers including oral squamous cell carcinoma (OSCC). Previously, we have demonstrated that fascin regulates actin polymerization and thereby promotes cell motility in K8-depleted OSCC cells. In the present study we have investigated the role of fascin in tumor progression of OSCC.</p> <p>Methods</p> <p>To understand the role of fascin in OSCC development and/or progression, fascin was overexpressed along with vector control in OSCC derived cells AW13516. The phenotype was studied using wound healing, Boyden chamber, cell adhesion, Hanging drop, soft agar and tumorigenicity assays. Further, fascin expression was examined in human OSCC samples (N = 131) using immunohistochemistry and level of its expression was correlated with clinico-pathological parameters of the patients.</p> <p>Results</p> <p>Fascin overexpression in OSCC derived cells led to significant increase in cell migration, cell invasion and MMP-2 activity. In addition these cells demonstrated increased levels of phosphorylated AKT, ERK1/2 and JNK1/2. Our in vitro results were consistent with correlative studies of fascin expression with the clinico-pathological parameters of the OSCC patients. Fascin expression in OSCC showed statistically significant correlation with increased tumor stage (<it>P </it>= 0.041), increased lymph node metastasis (<it>P </it>= 0.001), less differentiation (<it>P </it>= 0.005), increased recurrence (<it>P </it>= 0.038) and shorter survival (<it>P </it>= 0.004) of the patients.</p> <p>Conclusion</p> <p>In conclusion, our results indicate that fascin promotes tumor progression and activates AKT and MAPK pathways in OSCC-derived cells. Further, our correlative studies of fascin expression in OSCC with clinico-pathological parameters of the patients indicate that fascin may prove to be useful in prognostication and treatment of OSCC.</p

Severe Asthma Standard-of-Care Background Medication Reduction With Benralizumab: ANDHI in Practice Substudy

peer reviewedBackground: The phase IIIb, randomized, parallel-group, placebo-controlled ANDHI double-blind (DB) study extended understanding of the efficacy of benralizumab for patients with severe eosinophilic asthma. Patients from ANDHI DB could join the 56-week ANDHI in Practice (IP) single-arm, open-label extension substudy. Objective: Assess potential for standard-of-care background medication reductions while maintaining asthma control with benralizumab. Methods: Following ANDHI DB completion, eligible adults were enrolled in ANDHI IP. After an 8-week run-in with benralizumab, there were 5 visits to potentially reduce background asthma medications for patients achieving and maintaining protocol-defined asthma control with benralizumab. Main outcome measures for non–oral corticosteroid (OCS)-dependent patients were the proportions with at least 1 background medication reduction (ie, lower inhaled corticosteroid dose, background medication discontinuation) and the number of adapted Global Initiative for Asthma (GINA) step reductions at end of treatment (EOT). Main outcomes for OCS-dependent patients were reductions in daily OCS dosage and proportion achieving OCS dosage of 5 mg or lower at EOT. Results: For non–OCS-dependent patients, 53.3% (n = 208 of 390) achieved at least 1 background medication reduction, increasing to 72.6% (n = 130 of 179) for patients who maintained protocol-defined asthma control at EOT. A total of 41.9% (n = 163 of 389) achieved at least 1 adapted GINA step reduction, increasing to 61.8% (n = 110 of 178) for patients with protocol-defined EOT asthma control. At ANDHI IP baseline, OCS dosages were 5 mg or lower for 40.4% (n = 40 of 99) of OCS-dependent patients. Of OCS-dependent patients, 50.5% (n = 50 of 99) eliminated OCS and 74.7% (n = 74 of 99) achieved dosages of 5 mg or lower at EOT. Conclusions: These findings demonstrate benralizumab's ability to improve asthma control, thereby allowing background medication reduction. © 202

Deep and bottom water characteristics in the owen fracture zone, western Arabian Sea

48-49Hydro chemical studies at a station (10ᵒ34. l'N, 56ᵒ 31.7'E) in the Owen Fracture zone reveal an active movement of bottom water as approx ~ 75 m thick, cold, low-salinity layer. Silicate profile exhibits a broad maximum coinciding with a salinity maximum at about 3 km depth in conformity with earlier results. Within the benthic layer, an increase in AOU is observed associated with minor increases in nutrients, presumably due to the oxidation of particulate organic matter sinking from the surface layer

Dissolved copper, cadmium and lead in the coastal waters of Qatar, Arabian Gulf

143-149The concentrations of Cu, Pb and Cd have been determined in the exclusive economic zone of Qatar, Arabian Gulf during December 1993. Cathodic stripping voltammetry (CSV) was used both before and after UV destruction of organic matter in filtered samples, to differentiate between the total dissolved as well as the labile fractions. Metals distribution in the area is affected by the circulation pattern. Average total dissolved metals were 30.3 +/- 13.42, 8.53 +/- 4.37 and 0.61 +/- 0.46 nM kg(-1) for Cu, Pb and Cd, respectively. The organic fraction constituted on the average 37 +/- 13 % (Cu), 28 +/- 18 % (Ph) and 26 +/- 12 % (Cd) of the total dissolved metal indicating the affinity of Cu > Ph > Cd to form stable organic complexes. Significant relations appeared between organic Cu with both organic carbon and chlorophyll a. Inorganic Cd/reactive phosphorus ratio (average 1.46+0.73 nM:mu M-1) and inorganic Cu/reactive Si ratio (average 5.9 + 2.4 nM :mu M-1) were three orders of magnitude higher than the global ratios indicating nutrient deficiency in this part of the Gulf

DDT Concentration in Zooplankton from the Arabian Sea

54-55A few zooplankton samples from Arabian Sea, between Goa and Bombay, were analysed for total DDT content by GLC. Concentrations found, vary from 0.05 to 3.21 ppm (wet wt), depending on the extractable lipid content. Since the method, used, does not provide separation of polychlorinated biphenyls from DDT and its metabolites, it is suggested that the values may be accepted with some caution

Chemistry & Hydrography of the Andaman Sea

228-233Data collected during cruises 51 and 52 of R.V. Gaveshani (Jan-Feb 1979) indicate that watermasses on the eastern and western margins of the Andaman and Nicobar Islands have similar hydrographic features to a depth of about 1500m; deeper watermasses in the central Andaman basin are separated from the rest of the region by shallow sills and are relatively stagnant. Distribution of nutrients and nutrients-oxygen relationships indicate silicate concentrations and stoicchometric relations which are different from those reported for the Arabian Sea. Rates of denitrification (which terminates at the stage of formation of ammonia), however, appear to be uniform in the northern Indian Ocean

Chemical oceanography of the Arabian Sea: Part IV Laccadive Sea

215-221Data collected during the 10the (October 1976) and 31st (March-April 1978) cruises of R V Gaveshani suggest that water movements, considered typical of island-arc regions, are responsible for high levels of productivity observed in the Laccadive Sea. Patterns of distribution of nutrients and nutrients-oxygen relationships are similar to those observed in other parts of the Arabian Sea. High magnesium and low fluoride concentrations in the water indicate probable loss of the latter as insoluble ion-pairs and as apatites