Fwd: Identification of a Novel Immunogenic HLA-A*0201-Binding Epitope of HER-2/neu with Potent Antitumor Properties.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Sat, Jun 21, 2008 at 6:02 PM
Subject: Identification of a Novel Immunogenic HLA-A*0201-Binding Epitope of HER-2/neu with Potent Antitumor Properties.
To: mesothelioma77@gmail.com


[1]J Immunol. 2008 Jul 1; 181(1): 146-54
Gritzapis AD, Voutsas IF, Lekka E, Tsavaris N, Missitzis I, Sotiropoulou P, Perez S, Papamichail M, Baxevanis CN

HER-2/neu oncoprotein is overexpressed in a variety of human tumors and is associated with aggressive disease. Immunogenic HER-2/neu CTL epitopes have been used as vaccines for the treatment of HER-2/neu positive malignancies with limited success. By applying prediction algorithms for MHC class I ligands and proteosomal cleavages, in this study, we describe the identification of HER-2/neu decamer LIAHNQVRQV spanning residues 85-94 (HER-2(10(85))). HER-2(10(85)) proved to bind with high affinity to HLA-A2.1 and was stable for 4 h in an off-kinetics assay. This peptide was immunogenic in HLA-A2.1 transgenic (HHD) mice inducing peptide-specific CTL, which responded to tumor cell lines of various origin coexpressing human HER-2/neu and HLA-A2.1. This demonstrates that HER-2(10(85)) is naturally processed from endogenous HER-2/neu. Five of sixteen HER-2/neu(+) HLA-A2.1(+) breast cancer patients analyzed had HER-2(10(85))-reactive T cells ranging from 0.35-0.70% of CD8(+) T cells. Depletion of T regulatory cells from PBMC enabled the rapid expansion of HLA-A2.1/HER-2(10(85))pentamer(+)/CD8(+) cells (PENT(+)/CD8(+)), whereas significantly lower numbers of CTL could be generated from unfractionated PBMC. HER-2(10(85))-specific human CTL recognized the HER-2/neu(+) HLA-A2.1(+) tumor cell line SKBR3.A2, as determined by IFN-gamma intracellular staining and in the high sensitivity CD107alpha degranulation assay. Finally, HER-2(10(85)) significantly prolonged the survival of HHD mice inoculated with the transplantable ALC.A2.1.HER tumor both in prophylactic and therapeutic settings. These data demonstrate that HER-2(10(85)) is an immunogenic peptide, capable of eliciting CD8-mediated responses in vitro and in vivo, providing the platform for further exploitation of HER-2(10(85)) as a possible target for anticancer immunotherapy.



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Source: http://www.hubmed.org/display.cgi?uids=18566379
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Fwd: Emodin azide methyl anthraquinone derivative triggers mitochondrial-dependent cell apoptosis involving in caspase-8-mediated Bid cleavage.

---------- Forwarded message ----------
From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Sat, Jun 21, 2008 at 6:02 PM
Subject: Emodin azide methyl anthraquinone derivative triggers mitochondrial-dependent cell apoptosis involving in caspase-8-mediated Bid cleavage.
To: mesothelioma77@gmail.com


[1]Mol Cancer Ther. 2008 Jun; 7(6): 1688-97
Yan Y, Su X, Liang Y, Zhang J, Shi C, Lu Y, Gu L, Fu L

AMAD, an emodin azide methyl anthraquinone derivative, was extracted from the nature giant knotweed rhizome of traditional Chinese herbs. Here, we investigated the anticancer activities and signaling pathways implicated in AMAD-induced apoptosis in human breast cancer cell lines MDA-MB-453 and human lung adenocarcinoma Calu-3 cells. AMAD was found to have a potent cytotoxic effect on both cell lines. Hoechst 33258 staining and Annexin V/propidium iodide double staining exhibited the typical nuclear features of apoptosis and increased the proportion of apoptotic Annexin V-positive cells in a dose-dependent manner, respectively. Moreover, this apoptotic induction was associated with a collapse of the mitochondrial membrane potential and activated caspases (cysteine aspartase) cascade involving in caspase-8, caspase-9, caspase-3, and poly(ADP-ribose) polymerase cleavage in a concentration-dependent manner. It was noteworthy that AMAD also effectively cleaved Bid, a BH3 domain-containing proapoptotic Bcl-2 family member, and induced the subsequent release of cytochrome c from mitochondria into the cytosol. Furthermore, suppression of caspase-8 activity with Z-IETD-FMK partially inhibited release of cytochrome c and Bid cleavage induced by AMAD, whereas exposure to Z-LETD-FMK, a caspase-9 inhibitor, had no effect. Additionally, there was significant change in other mitochondrial membrane proteins triggered by AMAD, such as Bcl-xl and Bad. It was intriguing that AMAD decreased the generation of reactive oxygen species in both cell lines. DNA-binding assay exhibited apoptosis induced by AMAD was not involved in intercalating to DNA. Taken together, these data suggested that AMAD induced apoptosis via a mitochondrial pathway involving caspase-8/Bid activation in both cell lines. [Mol Cancer Ther 2008;7(6):1688-97].



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Source: http://www.hubmed.org/display.cgi?uids=18566240
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Fwd: Unknown primary cancer sites

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From: Search for lung cancer <rssfwd@rssfwd.com>
Date: Tue, Jun 24, 2008 at 6:16 AM
Subject: Unknown primary cancer sites
To: mesothelioma77@gmail.com

In 2005 cancers of unknown primary site represented around 4% of all new cases in New South Wales.

Tue, 24 Jun 2008 08:44:19 GMT

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Source: http://www.abc.net.au/rn/healthreport/stories/2008/2279761.htm
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Fwd: GSK releases cancer genomic data via caBIG

---------- Forwarded message ----------
From: Search for lung cancer <rssfwd@rssfwd.com>
Date: Tue, Jun 24, 2008 at 6:16 AM
Subject: GSK releases cancer genomic data via caBIG
To: mesothelioma77@gmail.com

Researchers at academic institutions, small research facilities and non-profit organizations may benefit by not having to incur the prohibitive cost and time involved in identifying and cataloging each cell ...

Tue, 24 Jun 2008 05:48:08 GMT

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Source: http://www.earlham.edu/~peters/fos/2008/06/gsk-releases-cancer-genomic-data-via_876.html
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