Eppley Institute for Research in Cancer and Allied Diseases

About: Eppley Institute for Research in Cancer and Allied Diseases is a based out in . It is known for research contribution in the topics: Pancreatic cancer & Cancer. The organization has 965 authors who have published 1396 publications receiving 58994 citations.

Molecular effectors of radiation resistance in colorectal cancer

Abstract: Evasion from apoptosis is critical for cancer development and progression. It is also a main reason for the resistance to anticancer therapy. Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer‐related mortality in the USA. Chemotherapy and radiation therapy are often combined with surgery to treat more advanced CRC patients. Although anticancer therapies have yielded a good success rate, the failure of treatment in over 90% of patients with advanced disease is due to resistance to the treatment, one of the biggest obstacles for effective cancer therapy. However, our knowledge of the molecular mechanisms that govern the resistance of CRC is very limited. No significant advance has been made to overcome the resistance. Therefore, there is an urgent need to identify molecules or pathways that can be targeted to overcome the resistance and improve cancer treatment. Expression of phosphatase of regenerating liver‐3 and survivin has been shown to correlate with advanced CRC, liver and lymph node metastases, high risk of recurrences, and worse patient survival. They have been implicated as important effectors in the resistance to anticancer therapy including radiation therapy in CRC. Their potential role in the resistance to radiation therapy makes them promising molecular targets to overcome radioresistance and increase efficacy of radiotherapy. The antagonists against phosphatase of regenerating liver‐3 and survivin could represent a novel type of molecular drug to be used in cancer treatment either as a single agent or, more likely, in combination with radiation or chemoradiation therapy.

N-Cadherin-Mediated Cell Motility Requires Cis Dimers

Abstract: Cadherins are expressed on the cell surface as a dimer in the membrane of one cell (cis dimer) that interacts with a cis dimer on an adjacent cell to form an adhesive trans dimer. It is well established that both cis and trans dimers must form for the cadherin to be an effective adhesion protein. In addition to their adhesive activity cadherins also play an important role in modulating cell behavior by regulating cell motility and signal transduction. Whether or not cis or trans dimers are necessary for the nonadhesive functions of cadherins has not been addressed. Here we show that N-cadherin cis dimers are necessary to induce cell motility in epithelial cells and that N-cadherin's ability to modulate the steady state levels of activated small GTPases requires both cis and trans dimers.

CFTR expression does not influence glycosylation of an epitope-tagged MUC1 mucin in colon carcinoma cell lines.

Abstract: 2To whom correspondence should be addressed The cause of the mucus clearance problems associated with cystic fibrosis remains poorly understood though it has been suggested that mucin hypersecretion, dehydration of mucins, and biochemical abnormalities in the glycosylation of mucins may be responsible. Since the biochemical and biophysical properties of a mucin are dependent on O-glycosylation, our aim was to evaluate the O-glycosylation of a single mucin gene product in matched pairs of cells that differed with respect to CFTR expression. An epitope-tagged MUC1 mucin cDNA (MUC1F) was used to detect variation in mucin glycosylation in stably transfected colon carcinoma cell lines HT29 and Caco2. The glycosylation of MUC1F mucin was evaluated in matched pairs of Caco2 cell lines that either express wild-type CFTR or have spontaneously lost CFTR expression. The general glycosylation pattern of MUC1F was evaluated by determining its reactivity with a series of monoclonal antibodies against known blood group and tumor-associated carbohydrate antigens. Metabolic labeling experiments were used to estimate the gross levels of glycosylation and sulfation of MUC1F mucin in these matched pairs of cell lines. Expression of CFTR in this experimental system did not affect the gross levels of glycosylation or sulfation of the MUC1F mucin nor the types of carbohydrates structures attached to the MUC1F protein.

Hepatic Deletion of Janus Kinase 2 Counteracts Oxidative Stress in Mice.

Abstract: Genetic deletion of the tyrosine kinase JAK2 or the downstream transcription factor STAT5 in liver impairs growth hormone (GH) signalling and thereby promotes fatty liver disease. Hepatic STAT5 deficiency accelerates liver tumourigenesis in presence of high GH levels. To determine whether the upstream kinase JAK2 exerts similar functions, we crossed mice harbouring a hepatocyte-specific deletion of JAK2 (JAK2Δhep) to GH transgenic mice (GHtg) and compared them to GHtgSTAT5Δhep mice. Similar to GHtgSTAT5Δhep mice, JAK2 deficiency resulted in severe steatosis in the GHtg background. However, in contrast to STAT5 deficiency, loss of JAK2 significantly delayed liver tumourigenesis. This was attributed to: (i) activation of STAT3 in STAT5-deficient mice, which was prevented by JAK2 deficiency and (ii) increased detoxification capacity of JAK2-deficient livers, which diminished oxidative damage as compared to GHtgSTAT5Δhep mice, despite equally severe steatosis and reactive oxygen species (ROS) production. The reduced oxidative damage in JAK2-deficient livers was linked to increased expression and activity of glutathione S-transferases (GSTs). Consistent with genetic deletion of Jak2, pharmacological inhibition and siRNA-mediated knockdown of Jak2 led to significant upregulation of Gst isoforms and to reduced hepatic oxidative DNA damage. Therefore, blocking JAK2 function increases detoxifying GSTs in hepatocytes and protects against oxidative liver damage.