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author:("genius, S")
1.  Cancer-testis antigen expression and immunogenicity in AL amyloidosis 
Blood Cancer Journal  2012;2(9):e90-.
Light-chain amyloidosis (AL) is a plasma cell dyscrasia closely related to multiple myeloma. In multiple myeloma, the cancer-testis antigens (CTAs) CT7 (MAGE-C1), CT10 (MAGE-C2) and MAGE-A CTAs are expressed in up to 80% of cases. In this study, we investigated the expression and immunogenicity of several CTAs in patients with AL amyloidosis in a total of 38 bone marrow specimens by employing standard immunohistochemistry techniques on paraffin-embedded archival tissues. Plasma samples from 35 patients (27 with matched bone marrow samples) were also analyzed by ELISA for sero reactivity to a group of full-length CTA proteins. CT7 was present in 25/38 (66%) while CT10 was demonstrated in 3/38 and GAGE in 1/38 AL amyloid cases. The expression pattern was mostly focal. There were no significant differences with regard to organ involvement, response to treatment, or prognosis in CTA positive compared to negative cases. None of the specimens showed spontaneous humoral immunity to CT7, but sero reactivity was observed in individual patients to other CTAs. This study identifies CT7 as the prevalent CTA in plasma cells of patients with AL amyloidosis. Further analyses determining the biology of CTAs in AL amyloidosis and their value as potential targets for immunotherapy are warranted.
doi:10.1038/bcj.2012.32
PMCID: PMC3461704  PMID: 22983433
AL amyloidosis; cancer-testis antigens; stem cell transplantation
2.  Role of JNK in mammary gland development and breast cancer 
Cancer Research  2011;72(2):472-481.
JNK signaling has been implicated in the developmental morphogenesis of epithelial organs. In this study we employed a compound deletion of the murine Jnk1 and Jnk2 genes in the mammary gland to evaluate the requirement for these ubiquitously expressed genes in breast development and tumorigenesis. JNK1/2 was not required for breast epithelial cell proliferation or motility. However, JNK1/2 deficiency caused increased branching morphogenesis and defects in the clearance of lumenal epithelial cells. In the setting of breast cancer development, JNK1/2 deficiency significantly increased tumor formation. Together, these findings established that JNK signaling is required for normal mammary gland development and that it has a suppressive role in mammary tumorigenesis.
doi:10.1158/0008-5472.CAN-11-1628
PMCID: PMC3261359  PMID: 22127926
3.  p38α Signaling Induces Anoikis and Lumen Formation During Mammary Morphogenesis 
Science signaling  2011;4(174):ra34.
The stress-activated protein kinase (SAPK) p38 can induce apoptosis, and its inhibition facilitates mammary tumorigenesis. We found that during mammary acinar morphogenesis in MCF-10A cells grown in three-dimensional culture, detachment of luminal cells from the basement membrane stimulated mitogen-activated protein kinase (MAPK) kinases 3 and 6 (MKK3/6) and p38α signaling to promote anoikis. p38α signaling increased transcription of the death-promoting protein BimEL by phosphorylating the activating transcription factor 2 (ATF-2) and increasing c-Jun protein abundance, leading to cell death by anoikis and acinar lumen formation. Inhibition of p38α or ATF-2 caused luminal filling reminiscent of that observed in ductal carcinoma in situ (DCIS). The mammary glands of MKK3/6 knockout mice (MKK3−/−/MKK6+/−) showed accelerated branching morphogenesis relative to those of wild-type mice, as well as ductal lumen occlusion due to reduced anoikis. This phenotype was recapitulated by systemic pharmacological inhibition of p38α and β (p38α/β) in wild-type mice. Moreover, the development of DCIS-like lesions showing marked ductal occlusion was accelerated in MMTV-Neu transgenic mice treated with inhibitors of p38α and p38β. We conclude that p38α is crucial for the development of hollow ducts during mammary gland development, a function that may be crucial to its ability to suppress breast cancer.
doi:10.1126/scisignal.2001684
PMCID: PMC3229273  PMID: 21610252
4.  Context-Dependent Transformation of Adult Pancreatic Cells by Oncogenic K-Ras 
Cancer cell  2009;16(5):379-389.
Summary
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies. To investigate the cellular origin(s) of this cancer, we determined the effect of PDAC-relevant gene mutations in distinct cell types of the adult pancreas. We show that a subpopulation of Pdx1-expressing cells is susceptible to oncogenic K-Ras induced transformation without tissue injury, whereas insulin-expressing endocrine cells are completely refractory to transformation under these conditions. However, chronic pancreatic injury can alter their endocrine fate and allow them to serve as the cell of origin for exocrine neoplasia. These results suggest that one mechanism by which inflammation and/or tissue damage can promote neoplasia is by altering the fate of differentiated cells that are normally refractory to oncogenic stimulation.
doi:10.1016/j.ccr.2009.09.027
PMCID: PMC3048064  PMID: 19878870

Results 1-4 (4)