15-Lipoxygenase-1 expression suppresses the invasive properties of colorectal carcinoma cell lines HCT-116 and HT-29

Colorectal carcinoma (CRC) is often lethal when invasion and/or metastasis occur. 15-Lipoxygenase-1 (15-LO-1), a member of the inflammatory eicosanoid pathway, oxidatively metabolizes linoleic acid and its expression is repressed in CRC. In this study, we investigated the hypothesis that the lack of 15-LO-1 expression in CRC cells might contribute to tumorigenesis. Therefore we introduced 15-LO-1 into HCT-116 and HT-29 cells that do not have detectable levels of 15-LO-1. Our data indicate that expression of 15-LO-1 significantly decreased cell proliferation and increased apoptosis. In addition, we observed a reduction in adhesion to fibronectin, anchorage-independent growth on soft agar, cellular motility and ability to heal a scratch wound, and migratory and invasive capacity across Matrigel. 15-LO-1 expression also reduced the expression of metastasis associated protein-1, a part of the nucleosome remodeling and histone deacetylase silencing complex. We propose that 15-LO-1 expression in CRC might contribute to the inhibition of metastatic capacity in vitro and can be exploited for therapeutic purposes. ( Cancer Sci 2009;100: 2283–2291)     

Growth-inhibitory effects of a mineralized extract from the red marine algae, Lithothamnion calcareum, on Ca-sensitive and Ca-resistant human colon carcinoma cells

Proliferation and differentiation were assessed in a series of human colon carcinoma cell lines in response to a mineral-rich extract derived from the red marine algae, Lithothamnion calcareum. The extract contains 12% Ca²⁺, 1% Mg²⁺, and detectable amounts of 72 trace elements, but essentially no organic material. The red algae extract was as effective as inorganic Ca²⁺ alone in suppressing growth and inducing differentiation of colon carcinoma cells that are responsive to a physiological level of extracellular Ca²⁺ (1.4 mM). However, with cells that are resistant to Ca²⁺ alone, the extract was still able to reduce proliferation and stimulate differentiation.     

Nutritional status of Kamar tribal children in Chhattisgarh

Objective  

Assessment of the nutritional status among 309 Kamar children (161 boys and 148 girls) aged 4–12 years.     

Use of bone marrow derived stem cells in a fracture non-union

This is an attempt of using in vitro cultured mesenchymal stem cells (MSCs) from bone marrow in joining of a fracture non-union. Bone marrow cells were obtained and differentially centrifuged for MSCs that were grown in vitro in mesenchymal stem cell basal medium aseptically, for 10 d. The cell mass was injected around the fracture non-union. Healthy conditions of development of tissue regeneration at the trauma site and due bone joining were recorded. It is concluded that in vitro cultured MSCs had a blithesome effect on the fracture non-union.     

The spectrum of neurological manifestations and genotype–phenotype correlation in Indian children with Gaucher disease

Gaucher disease (GD), one of the most frequent autosomal recessive lysosomal storage disorders, occurs due to bi-allelic pathogenic variants in the GBA1. Worldwide, the c.1448T>C (L483P) homozygous pathogenic variant is reported to be associated with neurological GD phenotype. Clinical distinction between GD1 and GD3 may be challenging due to subtle neurological features. Objective methods to evaluate neurological signs and saccades may help in early diagnosis. This study was conducted to assess the neurological phenotype, and its severity using a modified severity scoring tool (mSST), and the genotype–phenotype correlation. A total of 45 children aged 2 years 6 months to 15 years with a confirmed enzymatic and molecular diagnosis of GD with or without therapy were recruited. mSST tool was used to assess the severity of the neurological phenotype. A digital eye movement tracker (View Point Tracker) was used to assess eye movements. Clinical and genetic findings were analyzed. Out of 45 patients, 39 (86.7%) had at least one neurological phenotype detected using the mSST tool, with impairment of cognitive function (68.8%, 31/45) being the commonest feature. Thirty-two of 45 (71%) were assessed for saccadic eye movements using the eye tracker. Of these, 62.5% (20/32) had absent saccades. Four children (8.9%, 4/32) without clinical oculomotor apraxia had absent saccades on the viewpoint eye tracker. Overall, 77.7% (35/45), had homozygosity for c.1448T>C in GBA1 of which 91.4% (32/35) had neurological manifestations. Other alleles associated with neurological phenotype included c.1603C>T(p.R535C), c.1184C>T (p.S395F), c.115+1G>A (g.4234G>A), c.260G>A (p.R87Q) and c.1352A>G (p.Y451C). To conclude, in India, the c.1448T>C pathogenic variant in GBA1 is the commonest  and is associated with neurological phenotype of GD. Therefore, every patient of GD should be assessed using the mSST scoring tool for an early pick up of neurological features. The routine use of a viewpoint eye tracker in children with GD would be useful for early recognition of saccadic abnormalities.     

The conjugation of an AQP1-directed immunotoxin in the study of site-directed therapy within the CNS

Purpose  

The water channel, aquaporin (AQP)1, is highly specific to the choroid plexus (CP) epithelium within the brain. It is therefore a potential target through which therapeutic agents could be selectively directed to the CP. Here we describe the conjugation of a monoclonal antibody (mAb), raised against an extra-cellular domain of AQP1, to the A chain of ricin (RCA). This reagent should allow study of a highly specific chemical lesion of the CP.