I was able to sidle through the side door into Molecular Therapy. I came up with two proofs about 241 and two full length, free articles, one of which is the PI, the other is a review. The latter are from the January issue. The abstracts are apparently going to show up as articles in May.
>>Molecular Therapy
Article in Press, Corrected Proof
Melanoma differentiation-associated gene-7 protein physically associates with the double-stranded RNA-activated protein kinase PKR
Abujiang Pataer1 Stephan A. Vorburger2, Sunil Chada3, Siddharth Balachandran4, Glen N. Barber4, Jack A. Roth1, Kelly K. Hunt2 and Stephen G. Swisher1
1Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 445, Houston, TX 77030, USA
2Department of Surgical Oncology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 445, Houston, TX 77030, USA
3Introgen Therapeutics, Inc., Houston, TX 77030, USA
4Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, FL 33136, USA
Received 2 December 2004; accepted 27 January 2005. Available online 3 March 2005.
We previously reported that adenoviral-mediated overexpression of the melanoma differentiation-associated gene-7 (Ad-mda7; approved gene symbol IL24) leads to the rapid induction of PKR and activation of its downstream targets, resulting in apoptosis induction in human lung cancer cells. To evaluate the mechanism by which Ad-mda7 activates PKR, we studied the interaction between MDA-7 and PKR proteins. Following Ad-mda7 transduction of lung cancer cells, intracellular and extracellular MDA-7 protein was generated, leading to dose- and time-dependent PKR induction. Purified MDA-7 protein administered extracellularly did not induce PKR or apoptosis, suggesting that Ad-mda7-mediated PKR activation and apoptosis were not dependent on extracellular MDA-7 protein. Following Ad-mda7 transduction, RT-PCR demonstrated no increase in PKR mRNA levels despite increased levels of PKR protein, suggesting posttranscriptional regulation of PKR by MDA-7. Immunofluorescence and coimmunoprecipitation studies demonstrated that MDA-7 protein physically interacts with PKR. Transduction of PKR+/+ and PKR-/- transformed MEFs with Ad-mda7 demonstrated phosphorylated MDA-7 and PKR proteins in the lysates of PKR+/+ but not PKR-/- cells. These findings identify the first binding partner for MDA-7 and suggest that direct interaction between PKR and MDA-7 may be important for PKR activation and apoptosis induction, possibly through MDA-7 phosphorylation or activation of other downstream targets. <<
>>Molecular Therapy
Article in Press, Corrected Proof
mda-7/IL24 kills pancreatic cancer cells by inhibition of the Wnt/PI3K signaling pathways: Identification of IL-20 receptor-mediated bystander activity against pancreatic cancer
Sunil Chada1, 2, Dora Bocangel3, Rajagopal Ramesh3, Elizabeth A. Grimm2, John B. Mumm2, Abner M. Mhashilkar1 and Mingzhong Zheng1
1Introgen Therapeutics, Houston, TX 77030, USA
2Department of Experimental Therapeutics, University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030,USA
3Department of Thoracic and Cardiovascular Surgery, Houston, TX 77030,USA
Received 5 October 2004; accepted 11 December 2004. Available online 17 February 2005.
The melanoma differentiation-associated gene (mda-7; approved gene symbol IL24) is a tumor suppressor gene whose protein expression in normal cells is restricted to the immune system and to melanocytes. Recent studies have shown that mda-7 gene transfer inhibits cell growth and induces apoptosis in melanoma, lung cancer, breast cancer, and other tumor types through activation of various intracellular signaling pathways. In the current study, we demonstrate that Ad-mda7 transduction of human pancreatic cancer cells results in G2/M cell cycle arrest and cell killing. Cytotoxicity is mediated via apoptosis in a time- and dose-dependent manner. Tumor cell killing correlates with regulation of proteins involved in the Wnt and PI3K pathways: ß-catenin, APC, GSK-3, JNK, and PTEN. Additionally, we identify bystander cell killing activated by exposure of pancreatic tumor cells to secreted human MDA-7 protein. In pancreatic tumor cells, exogenous MDA-7 protein activates STAT3 and kills cells via engagement of IL-20 receptors. The specificity of bystander killing is demonstrated using neutralizing anti-MDA-7 antibodies and anti-receptor antibodies, which inhibit the apoptotic effects. In sum, we show that Ad-mda7 is able to induce growth inhibition and apoptosis in pancreatic cancer cells via inhibition of the Wnt/PI3K pathways and identify a novel bystander mechanism of MDA-7 killing in pancreatic cancer that functions via IL-20 receptors.<<
mda-7/IL-24: Exploiting Cancer's Achilles' Heel
sciencedirect.com!&_cdi=6964&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=5caf297d6f5897586afaae4437618e81
Intratumoral Injection of INGN 241, a Nonreplicating Adenovector Expressing the Melanoma-Differentiation Associated Gene-7 (mda-7/IL24): Biologic Outcome in Advanced Cancer Patients
sciencedirect.com!&_cdi=6964&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=b7a7e95bc4710b81ee9d1dc76a31200b
Those articles contains links to some other full text freebies of interest, in the references. Edit: no they don't. If these links work for you, you might want to print out these articles. Not sure how much longer that side door will be open.
Cheers, Tuck |
