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New Potential Targets (new + potential_target)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

siRNA-targeted COL8A1 inhibits proliferation, reduces invasion and enhances sensitivity to D -limonence treatment in hepatocarcinoma cells

IUBMB LIFE, Issue 1 2009
Yongfu Zhao
Abstract The COL8A1 (collagen type VIII, alpha-1) gene, which encodes the alpha 1 chain of collagen, type VIII, may modulate migration, proliferation and adherence of various cells. Only very sparse information exists on COL8A1 expression in hepatocarcinoma. To investigate the possible role of COL8A1 in the mouse hepatocarcinoma cell line Hca-F with highly metastatic potential in the lymph nodes, we used an RNA interference (RNAi) approach to silence COL8A1 expression. The results showed that a small interfering RNA (siRNA) targeted against COL8A1 significantly impeded Hca-F cells proliferation and colony formation in soft agar. This reduction of COL8A1 expression also led to the decreased invasion of Hca-F cells dramatically in vitro. Furthermore, the downregulation of COL8A1 expression also sensitized cells to the action of D -limonene. These data together provide insights into the function of COL8A1 and suggest that COL8A1 might represent a new potential target for gene therapy in hepatocarcinoma. © 2008 IUBMB IUBMB Life, 61(1): 74,79, 2009 [source]

Tumor-stromal crosstalk in invasion of oral squamous cell carcinoma: a pivotal role of CCL7

INTERNATIONAL JOURNAL OF CANCER, Issue 2 2010
Da-Woon Jung
Abstract Recent studies have shown that stromal fibroblasts have a more profound influence on the initiation and progression of carcinoma than was previously appreciated. This study aimed at investigating the reciprocal relationship between cancer cells and their associated fibroblasts at both the molecular and cellular level in oral squamous cell carcinoma (OSCC). To identify key molecular regulators expressed by carcinoma-associated fibroblasts (CAF) that promote cancer cell invasion, microarrays were performed by comparing cocultured OSCC cells and CAF with monoculture controls. Microarray and real-time PCR analysis identified marked upregulation of the chemokine (C-C motif) ligand 7 (CCL7) in cocultured CAF. ELISA showed an elevated level of CCL7 secretion from CAF stimulated by coculture with OSCC cells. CCL7 promoted the invasion and migration of OSCC cells, and the invasiveness was inhibited by treatment with CCL7 neutralizing antibody. OSCC cells were shown to express CCR1, CCR2 and CCR3, receptors for CCL7, by RT-PCR. In addition, treatment with anti-CCR1 or anti-CCR3 antibody inhibited CCL7-induced OSCC cell migration, implicating that CCL7 promotes cancer cell migration through CCR1 and CCR3 on OSCC cells. Cytokine antibody array analysis of the supernatant from OSCC cell culture revealed that interleukin-1, was an inducer of CCL7 secretion by CAF. This study confirms the reciprocal relationship of the molecular crosstalk regulating the invasion of OSCC and describes new potential targets for future therapy. [source]

Lack of oxygen in articular cartilage: consequences for chondrocyte biology

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 2 2010
Jérôme E. Lafont
Summary Controlling the chondrocytes phenotype remains a major issue for cartilage repair strategies. These cells are crucial for the biomechanical properties and cartilage integrity because they are responsible of the secretion of a specific matrix. But chondrocyte dedifferentiation is frequently observed in cartilage pathology as well as in tissue culture, making their study more difficult. Given that normal articular cartilage is hypoxic, chondrocytes have a specific and adapted response to low oxygen environment. While huge progress has been performed on deciphering intracellular hypoxia signalling the last few years, nothing was known about the particular case of the chondrocyte biology in response to hypoxia. Recent findings in this growing field showed crucial influence of the hypoxia signalling on chondrocytes physiology and raised new potential targets to repair cartilage and maintain tissue integrity. This review will thus focus on describing hypoxia-mediated chondrocyte function in the native articular cartilage. [source]

Nod1, Nod2 and Nalp3 receptors, new potential targets in treatment of allergic rhinitis?

ALLERGY, Issue 10 2010
J. Bogefors
To cite this article: Bogefors J, Rydberg C, Uddman R, Fransson M, Månsson A, Benson M, Adner M, Cardell LO. Nod1, Nod2 and Nalp3 receptors, new potential targets in treatment of allergic rhinitis? Allergy 2010; 65: 1222,1226. Abstract Background:, Recently, a new set of pattern-recognition receptors, the nucleotide-binding oligomerization domain (Nod)-like receptors (NLRs), have emerged. Their activation, either by allergens or microbes, triggers an inflammatory response. The knowledge about NLRs in human airways is limited. Aim of the study:, To investigate presence of NLRs in the human nose of healthy individuals and patients with intermittent allergic rhinitis outside and during pollen season. Methods:, The expression of Nod1, Nod2, and Nalp3 in nasal biopsies was determined with real-time RT-PCR and immunohistochemistry. Cultured primary human nasal epithelial cells (HNECs) were analyzed using real-time RT-PCR and flow cytometry to further verify the presence of NLRs in the epithelium. Results:, Immunohistochemical analysis revealed presence of Nod1, Nod2, and Nalp3 in the nasal epithelium. This was corroborated in cultured HNECs. Patients suffering from symptomatic allergic rhinitis exhibited lower Nod1 and Nalp3 mRNA levels than both controls and patients during pollen season. Nod2 expression was found in all specimens tested, but no differences were seen between the three groups. Conclusion:, Nod1, Nod2, and Nalp3 receptors were found to be present in the human nose. The expression of Nod1 and Nalp3 were down-regulated during pollen season among patients with allergic rhinitis. This opens up for new insights and novel therapeutic strategies in inflammatory airway disease. [source]