Role of Increased n-acetylaspartate Levels in Cancer.
JNCI Journal of the National Cancer Institute 108(6):djv426 (2016)
The clinical and biological effects of metabolic alterations in cancer are not fully understood.
In high-grade serous ovarian cancer (HGSOC) samples (n = 101), over 170 metabolites were profiled and compared with normal ovarian tissues (n = 15). To determine NAT8L gene expression across differen...
A miR-192-EGR1-HOXB9 regulatory network controls the angiogenic switch in cancer.
Nature Communications 7:11169 (2016)
A deeper mechanistic understanding of tumour angiogenesis regulation is needed to improve current anti-angiogenic therapies. Here we present evidence from systems-based miRNA analyses of large-scale patient data sets along with in vitro and in vivo experiments that miR-192 is a key regulator of ...
A genome-scale screen reveals context-dependent ovarian cancer sensitivity to miRNA overexpression.
Molecular Systems Biology 11(12):842 (2015)
Large-scale molecular annotation of epithelial ovarian cancer (EOC) indicates remarkable heterogeneity in the etiology of that disease. This diversity presents a significant obstacle against intervention target discovery. However, inactivation of miRNA biogenesis is commonly associated with adva...
Biphasic components of sarcomatoid clear cell renal cell carcinomas are molecularly similar to each other, but distinct from, non-sarcomatoid renal carcinomas.
The Journal of Pathology: Clinical Research 1(4):212 (2015)
Sarcomatoid transformation, wherein an epithelioid carcinomatous tumour component coexists with a sarcomatoid histology, is a predictor of poor prognosis in clear cell renal cell carcinoma. Our understanding of sarcomatoid change has been hindered by the lack of molecular examination. Thus, we s...
Intratumoral morphologic and molecular heterogeneity of rhabdoid renal cell carcinoma: challenges for personalized therapy.
Modern Pathology 28(9):1225 (2015)
Rhabdoid histology in clear-cell renal cell carcinoma is associated with a poor prognosis. The prognosis of patients with clear-cell renal cell carcinoma may also be influenced by molecular alterations. The aim of this study was to evaluate the association between histologic features and salient...
A Phase I/II Study of the mTOR Inhibitor Everolimus in Combination with HyperCVAD Chemotherapy in Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia.
Clinical Cancer Research 21(12):2704 (2015)
Previous studies suggest a potential therapeutic role for mTOR inhibition in lymphoid malignancies. This single-center phase I/II study was designed to test the safety and efficacy of the mTOR inhibitor everolimus in combination with HyperCVAD chemotherapy in relapsed/refractory acute lymphoblas...
Clinically relevant microRNAs in ovarian cancer.
Molecular Cancer Research 13(3):393 (2015)
microRNAs (miRNAs/miRs) belong to a class of small noncoding RNAs that can negatively regulate messenger RNA (mRNA) expression of target genes. miRNAs are involved in multiple aspects of ovarian cancer cell dysfunction and the phenotype of ovarian cancer cells can be modified by targeting miRNA ...
Expression of sulfotransferase SULT1A1 in cancer cells predicts susceptibility to the novel anticancer agent NSC-743380.
Oncotarget 6(1):345 (2015)
The small molecule anticancer agent NSC-743380 modulates functions of multiple cancer-related pathways and is highly active in a subset of cancer cell lines in the NCI-60 cell line panel. It also has promising in vivo anticancer activity. However, the mechanisms underlying NSC-743380's selective...
Optimized Prediction of Extreme Treatment Outcomes in Ovarian Cancer.
Cancer Informatics 14(Suppl 5):45 (2015)
Ovarian cancer is the fifth leading cause of death among female cancers. Front-line therapy for ovarian cancer is platinum-based chemotherapy. However, the response of patients is highly nonuniform. The TCGA database of serous ovarian carcinomas shows that ~10% of patients respond poorly to plat...
BRCA2 inhibition enhances cisplatin-mediated alterations in tumor cell proliferation, metabolism, and metastasis.
Molecular Oncology 8(8):1429 (2014)
Tumor cells have unstable genomes relative to non-tumor cells. Decreased DNA integrity resulting from tumor cell instability is important in generating favorable therapeutic indices, and intact DNA repair mediates resistance to therapy. Targeting DNA repair to promote the action of anti-cancer a...
Reverse-phase protein array for prediction of patients at low risk of developing bone metastasis from breast cancer.
Oncologist 19(9):909 (2014)
A biomarker that predicts bone metastasis based on a protein laboratory assay has not been demonstrated. Reverse-phase protein array (RPPA) enables quantification of total and phosphorylated proteins, providing information about their functional status. The aim of this study was to identify bone...
Focal adhesion kinase: an alternative focus for anti-angiogenesis therapy in ovarian cancer.
Cancer Biology & Therapy 15(7):919 (2014)
This investigation describes the clinical significance of phosphorylated focal adhesion kinase (FAK) at the major activating tyrosine site (Y397) in epithelial ovarian cancer (EOC) cells and tumor-associated endothelial cells. FAK gene amplification as a mechanism for FAK overexpression and the ...
Molecular biomarkers of residual disease after surgical debulking of high-grade serous ovarian cancer.
Clinical Cancer Research 20(12):3280 (2014)
Residual disease following primary cytoreduction is associated with adverse overall survival in patients with epithelial ovarian cancer. Accurate identification of patients at high risk of residual disease has been elusive, lacking external validity and prompting many to undergo unnecessary surg...
Notch3 pathway alterations in ovarian cancer.
Cancer Research 74(12):3282 (2014)
The Notch pathway plays an important role in the growth of high-grade serous ovarian (HGS-OvCa) and other cancers, but its clinical and biologic mechanisms are not well understood. Here, we found that the Notch pathway alterations are prevalent and significantly related to poor clinical outcome ...
Preclinical and early clinical evaluation of the oral AKT inhibitor, MK-2206, for the treatment of acute myelogenous leukemia.
Clinical Cancer Research 20(8):2226 (2014)
Recent studies suggested that AKT activation might confer poor prognosis in acute myelogenous leukemia (AML), providing the rationale for therapeutic targeting of this signaling pathway. We, therefore, explored the preclinical and clinical anti-AML activity of an oral AKT inhibitor, MK-2206. Exp...
Most expression and splicing changes in myotonic dystrophy type 1 and type 2 skeletal muscle are shared with other muscular dystrophies.
Neuromuscular Disorders 24(3):227 (2014)
The prevailing pathomechanistic paradigm for myotonic dystrophy (DM) is that aberrant expression of embryonic/fetal mRNA/protein isoforms accounts for most aspects of the pleiotropic phenotype. To identify aberrant isoforms in skeletal muscle of DM1 and DM2 patients, we performed exon-array prof...
2'-OMe-phosphorodithioate-modified siRNAs show increased loading into the RISC complex and enhanced anti-tumour activity.
Nature Communications 5:3459 (2014)
Improving small interfering RNA (siRNA) efficacy in target cell populations remains a challenge to its clinical implementation. Here, we report a chemical modification, consisting of phosphorodithioate (PS2) and 2'-O-Methyl (2'-OMe) MePS2 on one nucleotide that significantly enhances potency and...
Targeting SRC and tubulin in mucinous ovarian carcinoma.
Clinical Cancer Research 19(23):6532 (2013)
To investigate the antitumor effects of targeting Src and tubulin in mucinous ovarian carcinoma.
The in vitro and in vivo effects and molecular mechanisms of KX-01, which inhibits Src pathway and tubulin polymerization, were examined in mucinous ovarian cancer models.
In vitro studies using RMUG...
Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes.
Clinical Cancer Research 19(19):5533 (2013)
The clinical relevancy of the 7-subtype classification of triple-negative breast cancer (TNBC) reported by Lehmann and colleagues is unknown. We investigated the clinical relevancy of TNBC heterogeneity by determining pathologic complete response (pCR) rates after neoadjuvant chemotherapy, based...
Independent validation of a model using cell line chemosensitivity to predict response to therapy.
JNCI Journal of the National Cancer Institute 105(17):1284 (2013)
Methods using cell line microarray and drug sensitivity data to predict patients' chemotherapy response are appealing, but groups may be reluctant to release details to preserve intellectual property. Here we describe a case study to validate predictions while treating the methods as a "black bo...