Cancer Publications
1. The following studies addressed the active role of cancer cells as immune modulators and demonstrated that ovarian cancer cells have the capacity to promote cell death of activated immune cells. Through the expression of Fas Ligand (FasL) ovarian cancer cells can eliminate T cells that represent a danger for the tumor. We demonstrated that this process could be obtained either by direct cell to cell contact or by release of microvesicles containing FasL.
a)Song J, Sapi E, Brown WD, Nilsen J, Naftolin F, Mor G (2000) Mammary Gland Remodeling: Expression and Role of the Fas/Fas Ligand System during Pregnancy, Lactation and Involution. Journal of Clinical Investigation. 106:1209-1224.
b)Song R, Mor G, McPherson RA, Song J, Zhang Z, Wang P, Santen RJ. (2001) Activation of Fas/FasL pathway linked estrogen-induced apoptosis in human breast cancer cells. Journal of the National Cancer Institute. 93:1714-1723
c)Abrahams V, Straszewski S, Kamsteeg M, Hanczaruk B, Schwartz PE, Rutherford TJ, Mor G (2003) Epithelial Ovarian Cancer Cells secrete Functional Fas Ligand. Cancer Research: 63(17):5573-5581
2. The following studies represent our efforts to develop new therapeutic approaches for the treatment of ovarian cancer. We demonstrated that by targeting the apoptotic cascade we could sensitize cancer cells to chemotherapy. We have performed the molecular, cellular and preclinical characterization of several compounds, which have reached the clinic and are, or were, in clinical trials.
a)Kamsteeg M, Rutherford T, Sapi E, Shahabi S, Brown D, and Mor G (2003) Phenoxodiol Induces Fas-Mediated Apoptosis Of Ovarian Cancer Cells. Oncogene: 22:2611-2620
b)Alvero A, O’Malley D, Brown D, Kelly G, Garg M, Chen W, Rutherford T, Mor G (2006) Molecular mechanisms of Phenoxodiol-induced Chemo-sensitivity in Refractory Ovarian Cancer. Cancer: 106(3):599-608.
c)Chen R, Alvero A, Silasi, D-A, Kelly M, Fest, S, Leiser A, Schwartz P, Rutherford T, Visintin I, Mor G (2008) Regulation of IKKβ by mir-199 affects NF-κB activity in ovarian cancer cells. Oncogene: Apr 14:1-12
d)Alvero AB, Montagna MK, Chen R, Kim KH, Kyungjin K, Visintin I, Fu HH, Brown D, Mor G. (2009) NV-128, a novel isoflavone derivative, induces caspase-independent cell death through the Akt/mammalian target of rapamycin pathway Cancer Jul 15;115(14):3204-16. PMID:19472408
3. The best treatment for cancer is its early detection. We have made significant efforts to the identification and characterization of biological markers that could help the early detection of the disease and share insights into the biology of the disease.
a)Hudson ME, Pozdnyakova I, Haines K, Mor G, Snyder M (2007) Identification of differentially expressed proteins in ovarian cancer using high-density protein microarrays. ProcNatlAcadSci U S A. Oct 22
b)Flick M, O’Malley D, Rutherford T, Rodov S, Kamsteeg M, Hao XY, Schwartz P, Kacinski B, Mor G. (2004) Apoptosis-Based Evaluation of Chemosensitivity in Ovarian Cancer Patients. Journal of the Society for Gynecologic Investigation. 11/4: 252-259
c)Agarwal R, AlveroA, VisintinI, Lai Y, Schwartz P, Rutherford, T, Ward D, and Mor G (2007) Macrophage Migration Inhibitory Factor expression in ovarian cancer. American Journal of Obstetrics and Gynecology 196(4):348.e1-5
d)Visintin I, Alvero A, Lai Y, Tenthorey J, Leiser A, Flores R, Rutherford T, Schwartz P, Ward D, Mor G, (2008) Diagnostic Markers for Early Detection of Ovarian Cancer, Clinical Cancer Research. 14(4):1065-72
4.Our research has focused on understanding the role of ovarian cancer stem cells in the formation progression and recurrence of ovarian cancer as well as in the process of chemoresistance. We were one of the first ones to isolate and clone ovarian cancer cells with tumor initiating properties and have extensively characterized them. Our research has demonstrated that these cells are resistant to conventional chemotherapy and therefore are responsible for recurrence and carcinoamtosis. We have developed in vitro and in vivo models to study their function and to develop new therapies targeting these chemoresistant cells..
a)Alvero A, Chen R, Fu H, Montagna M, Schwartz PE, Rutherford T, Silasi D-A, Steffensen KD, Waldstrom M, Visintin I, and Mor G (2009) Molecular phenotyping of human ovarian cancer stem cells unravel the mechanisms for repair and chemo-resistance. Cell Cycle: 8: 158-166
b)Alvero AB, Fu HH, Holmberg J, Visintin I, Mor L, Marquina CC, Oidtman J, Silasi DA, Mor G. 2009 Stem-Like Ovarian Cancer Cells can serve as tumor vascular progenitors, Stem Cell: 27:2405-2413
c)Steffensen KD, Alvero AB, Yang Y, Waldstrom M, Hui P, Holmberg JC, Silasi DA, Jakobsen A, Rutherford T, Mor G (2011) Prevalence of epithelial ovarian cancer stem cells correlates with recurrence in early-stage ovarian cancer. Journal of Oncology. 2011:620523 PMID21904548
d)Alvero AB, Montagna MK, Holmberg JC, Craveiro V, Brown D, Mor G (2011) Targeting the mitochondria activates two independent cell death pathways in ovarian cancer stem cells. Molecular Cancer Therapy. Aug;10(8):1385-93 PMID21677151
e)CraveiroV, Yang-Hartwich Y, Holmberg JC, Sumi NJ, Pizzonia J, Griffin B, Gill SK, Silasi DA, Azodi M, Rutherford T, Alvero AB,MorG (2013). Phenotypic modifications in ovarian cancer stem cells following Paclitaxel treatment.Cancer Med. 2013 Dec;2(6):751-62
f)Sumi NJ, Lima E, Pizzonia J, Orton SP,CraveiroV, Joo W, Holmberg JC, Gurrea M, Yang-Hartwich Y, Alvero A,MorG (2014) Murine model for non-invasive imaging to detect and monitor ovarian cancer recurrence. J Vis Exp. 2014 Nov 2;(93):e51815
g)Yang-Hartwich Y, Soteras MG, Lin ZP, Holmberg J, Sumi N,CraveiroV, Liang M, Romanoff E, Bingham J, Garofalo F, Alvero A,MorG (2015) p53 protein aggregation promotes platinum resistance in ovarian cancer.Oncogene. 2015 Jul;34(27):3605-16
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