John A Copland

Mayo Clinic - Rochester, Rochester, Minnesota, United States

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Publications (87)391.31 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Context: Currently there are no efficacious therapies for patients with anaplastic thyroid carcinoma (ATC) that result in long term disease stabilization or regression. Objective: We sought to identify pathways critical for ATC cell progression and viability in an effort to develop new therapeutic strategies. We investigated the effects of targeted inhibition of stearoyl-CoA desaturase 1 (SCD1), a constituent of fatty acid metabolism over-expressed in ATC. Design: Gene-array of ATC and normal thyroid tissue was performed to identify gene transcripts demonstrating altered expression in tumor samples. Effects of pharmacologic and genetic inhibition of SCD1 on tumor cell viability as well as cell signaling responses to therapy were evaluated in in vitro and in vivo models of this rare, lethal malignancy. Results: Gene-array analysis revealed consistent distortion of fatty acid metabolism and overexpression of SCD1 in ATC and well-differentiated thyroid carcinomas. SCD1 is critical for ATC cell survival and proliferation, inhibition of which induced endoplasmic reticulum (ER) stress, activation of the unfolded protein response (UPR), and apoptosis. Combined suppression of ER-associated degradation (ERAD), a pro-survival component of the UPR, using proteasome inhibitors resulted in a synergistic decrease in tumor cell proliferation and increased cell death. Conclusions: SCD1 is a novel oncogenic factor specifically required for tumor cell viability in ATC. Furthermore, expression of SCD1 appears to be correlated with thyroid tumor aggressiveness, and may serve as a prognostic biomarker. These findings substantiate SCD1 as a novel tumor-specific target for therapy in patients with ATC, and should be further investigated in a clinical setting.
    The Journal of clinical endocrinology and metabolism. 02/2015;
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    ABSTRACT: Context and Objective: Oncocytic thyroid carcinoma, also known as Hürthle cell thyroid carcinoma, accounts for only a small percentage of all thyroid cancers. However, this malignancy often presents at an advanced stage and poses unique challenges to patients and clinicians. Surgical resection of the tumor accompanied in some cases by radioactive iodine treatment, radiation and chemotherapy are the established modes of therapy. Knowledge of the perturbed oncogenic pathways can provide better understanding of the mechanism of disease and thus opportunities for more effective clinical management. Design and Patients: Initially, two oncocytic thyroid carcinomas and their matched normal tissues were profiled using whole genome sequencing. Subsequently, 72 oncocytic thyroid carcinomas, one cell line and 5 Hürthle cell adenomas were examined by targeted sequencing for the presence of mutations in the multiple endocrine neoplasia I (MEN1) gene. Results: Here we report the identification of MEN1 loss-of-function mutations in 4% of patients diagnosed with oncocytic thyroid carcinoma. Whole genome sequence data also revealed large regions of copy number variation encompassing nearly the entire genomes of these tumors. Conclusion: Menin, a ubiquitously expressed nuclear protein, is a well-characterized tumor suppressor whose loss is the cause of multiple endocrine neoplasia type 1 syndrome. Menin is involved in several major cellular pathways such as regulation of transcription, control of cell cycle, apoptosis and DNA damage repair pathways. Mutations of this gene in a subset of Hürthle cell tumors point to a potential role for this protein and its associated pathways in thyroid tumorigenesis.
    The Journal of clinical endocrinology and metabolism. 01/2015;
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    ABSTRACT: A 46-year-old female presents with a pelvic mass and is diagnosed as having a high-grade endometrial stromal sarcoma. During surgery, she is noted to have areas of intussusception of the small bowel secondary to large hamartomatous polyps. The patient had a previous history of small bowel obstruction secondary to what had been thought to be hyperplastic polyps but represented hamartomatous polyps on further review. Additional examination revealed the presence of subtle hyperpigmented macules on the fingers leading to a diagnosis of Peutz-Jeghers Syndrome (PJS). The diagnosis was confirmed by the presence of a germ-line STK11 mutation. Immunohistochemistry analysis of the tumor showed decreased expression of STK-11 as compared to one of the patient's hamartomatous polyps. Next generation sequencing of the tumor specimen failed to demonstrate a "second hit" somatic mutation in STK-11. This case represents the first case of endometrial stromal sarcoma associated with PJS and illustrates the importance of increased awareness of this condition among oncologists. PJS is associated with dysregulation of the mTOR pathway; treatment with an mTOR inhibitor was not effective in this case.
    Hereditary Cancer in Clinical Practice 01/2015; 13(1):6. · 1.71 Impact Factor
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    ABSTRACT: Context: Anaplastic thyroid carcinoma (ATC) is one of the most deadly human malignancies. It is 99 percent lethal, and patients have a median survival of only 6 months after diagnosis. Despite these grim statistics, the mechanism underlying the tumorigenic capability of ATC cells is unclear. Objective: S100A8 and S100A9 proteins have emerged as critical mediators in cancer. The aim was to investigate the expression and function of S100A8 and S100A9 in ATC and the mechanisms involved. Design: We determined the expression of S100A8 and S100A9 in human ATC by gene array analysis and immunohistochemistry. Using RNAi-mediated stable gene knockdown in human ATC cell lines and bioluminescent imaging of orthotopic and lung metastasis mouse models of human ATC, we investigated the effects of S100A8 and S100A9 on tumorigenesis and metastasis. Results: We demonstrated that S100A8 and S100A9 were overexpressed in ATC but not in other types of thyroid carcinomas. In vivo analysis in mice using ATC cells that had S100A8 knocked down revealed reduced tumor growth and lung metastasis, as well as significantly prolonged animal survival. Mechanistic investigations showed that S100A8 promotes ATC cell proliferation through an interaction with RAGE, which activates the p38, ERK1/2 and JNK signaling pathways in the tumor cells. Conclusions: These findings establish a novel role for S100A8 in the promoting and enhancing of ATC progression. They further suggest that the inhibition of S100A8 could represent a relevant therapeutic target, with the potential of enabling a more effective treatment path for this deadly disease.
    Journal of Clinical Endocrinology &amp Metabolism 11/2014; 100(2):jc20142988. · 6.31 Impact Factor
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    ABSTRACT: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer, and has the highest propensity to manifest as metastatic disease. Recent characterizations of the genetic signature of ccRCC have revealed several factors correlated with tumor cell migration and invasion; however the specific events driving malignancy are not well defined. Furthermore, there remains a lack of targeted therapies that result in long-term, sustainable response in patients with metastatic disease. We show here that neuronal pentraxin 2 (NPTX2) is over-expressed specifically in ccRCC primary tumors and metastases, and that it contributes to tumor cell viability and promotes cell migration through its interaction with the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR4. We propose NPTX2 as a novel molecular target for therapy for ccRCC patients diagnosed with or at risk of developing metastatic disease.
    Cancer Research 06/2014; · 9.28 Impact Factor
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    ABSTRACT: Currently there is a lack of targeted therapies that lead to long-term attenuation or regression of disease in patients with advanced clear cell renal cell carcinoma (ccRCC). Our group has implemented a high-throughput genetic analysis coupled with a high-throughput proliferative screen in order to investigate the genetic contributions of a large cohort of overexpressed genes at the functional level in an effort to better understand factors involved in tumor initiation and progression. Patient gene array analysis identified transcripts that are consistently elevated in patient ccRCC as compared to matched normal renal tissues. This was followed by a high-throughput lentivirus screen, independently targeting 195 overexpressed transcripts identified in the gene array in four ccRCC cell lines. This revealed 31 'hits' that contribute to ccRCC cell proliferation. Many of the hits identified are not only presented in the context of ccRCC for the first time, but several have not been previously linked to cancer. We further characterize the function of a group of hits in tumor cell invasion. Taken together these findings reveal pathways that may be critical in ccRCC tumorigenicity, and identifies novel candidate factors that could serve as targets for therapeutic intervention or diagnostic/prognostic biomarkers for patients with advanced ccRCC.
    Oncotarget 06/2014; · 6.63 Impact Factor
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    ABSTRACT: Context:The BRAF V600E mutation (BRAF-MUT) confers an aggressive phenotype in papillary thyroid carcinoma, but unidentified additional genomic abnormalities may be required for full phenotypic expression.Objective:RNA sequencing (RNA-Seq) was performed to identify genes differentially expressed between BRAF-MUT and BRAF wild-type (BRAF-WT) tumors and to correlate changes to patient clinical status.Design:BRAF-MUT and BRAF-WT tumors were identified in patients with T1N0 and T2-3N1 tumors. Gene expression levels were determined (RNA-Seq) and fusion transcripts were detected. Multiplexed capture/detection and digital counting of mRNA transcripts (nCounter, NanoString Technologies) validated RNA-Seq data for immune system-related genes.Setting:Referral medical center.Patients:BRAF-MUT patients included nine women, three men; nine were TNM stage I and three were stage III. Three (25%) had tumor infiltrating lymphocytes. BRAF-WT included five women, three men; all were stage I, and five (62.5%) had tumor infiltrating lymphocytes.Results:RNA-Seq identified 560 of 13 t085 genes differentially expressed between BRAF-MUT and BRAF-WT tumors. Approximately 10% of these genes were related to MetaCore immune function pathways; 51 were underexpressed in BRAF-MUT tumors, whereas 4 (HLAG, CXCL14, TIMP1, IL1RAP) were overexpressed. The four most differentially overexpressed immune genes in BRAF-WT tumors (IL1-B; CCL19; CCL21; CXCR4) correlated with lymphocyte infiltration. nCounter confirmed the RNA-Seq expression level data. Eleven different high-confidence fusion transcripts were detected (four interchromosomal; seven intrachromosomal) in 13 of 20 tumors. All in-frame fusions were validated by RT-PCR.Conclusion:BRAF-MUT papillary thyroid cancers have reduced expression of immune/inflammatory response genes compared with BRAF-WT tumors and correlate with lymphocyte infiltration. In contrast, HLA-G and CXCL14 are overexpressed in BRAF-MUT tumors. Sixty-five percent of tumors had between one and three fusion transcripts. Functional studies will be required to determine the potential role of these newly identified genomic abnormalities in contributing to the aggressiveness of BRAF-MUT and BRAF-WT tumors.
    The Journal of Clinical Endocrinology and Metabolism 12/2013; · 6.31 Impact Factor
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    ABSTRACT: To examine the ability of dual mTORc1/c2 inhibitors in conjunction with lapatinib to function in a synergistic manner to inhibit cell proliferation and anchorage-independent growth in bladder cancer cell lines. We examined patient tumor samples for overexpression of pS6, p4EBP1, pAkt, and phosphorylated epidermal growth factor receptor (pEGFR) using a tissue microarray containing 84 cases. Three bladder cancer cell lines, T24, HT1376, and UM-UC-3, were analyzed for cell proliferation after treatment with mTORc1/c2 inhibitors OSI-027 or PP242. Western blots were used to verify that the drugs were inhibiting phosphorylation of target proteins within the mTOR pathway, and they were compared with rapamycin inhibition. We also analyzed cell proliferation and anchorage-independent growth after treatment with OSI-027 and lapatinib in combination. PARP cleavage and autophagic flux were measured by examining levels of LC3B and p62 by western blotting. Tumor samples show increased expression of pEGFR (38% vs. 8%) and HER2 (38% vs. 4%) and decreased expression of pAkt S473 (7.5% vs. 29%) and pAkt T308 (50% vs. 84%) relative to normal tissue. Significant differences between normal and tumor samples for staining with pEGFR (P = 0.0188), HER 2 (P = 0.0017), pATK S473 (P = 0.0128), and pAkt T308 (P = 0.0015) is observed. Expression of proteins within the EGFR/HER2 pathway or within the mTOR pathway is correlated. No correlation was found between staining and tumor stage. OSI-027 and PP242 diminish cell proliferation in all 3 cell lines with IC50 values ranging from 0.63 to 17.95µM. Both drugs inhibit phosphorylation of both mTORc1 and mTORc2 pathway components. OSI-027 and lapatinib inhibit cell proliferation and anchorage-independent growth in a synergistic manner. One cell line exhibited apoptosis in response to combination drug treatment, whereas the other 2 cell lines have increased levels of autophagy indicative of resistance to apoptosis. The combination of OSI-027 and lapatinib results in antitumor synergy and further exploration of this combination should be undertaken.
    Urologic Oncology 09/2013; · 3.36 Impact Factor
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    ABSTRACT: Primary CNS lymphoma carries a poor prognosis. Novel therapeutic agents are urgently needed. Pomalidomide (POM) is a novel immunomodulatory drug with anti-lymphoma activity. CNS pharmacokinetic analysis was performed in rats to assess the CNS penetration of POM. Preclinical evaluation of POM was performed in two murine models to assess its therapeutic activity against CNS lymphoma. The impact of POM on the CNS lymphoma immune microenvironment was evaluated by immunohistochemistry and immunofluorescence. In vitro cell culture experiments were carried out to further investigate the impact of POM on the biology of macrophages. POM crosses the blood brain barrier with CNS penetration of ~ 39%. Preclinical evaluations showed that it had significant therapeutic activity against CNS lymphoma with significant reduction in tumor growth rate and prolongation of survival, that it had a major impact on the tumor microenvironment with an increase in macrophages and natural killer cells, and that it decreased M2-polarized tumor-associated macrophages and increased M1-polarized macrophages when macrophages were evaluated based on polarization status. In vitro studies using various macrophage models showed that POM converted the polarization status of IL4-stimulated macrophages from M2 to M1, that M2 to M1 conversion by POM in the polarization status of lymphoma-associated macrophages is dependent on the presence of NK cells, that POM induced M2 to M1 conversion in the polarization of macrophages by inactivating STAT6 signaling and activating STAT1 signaling, and that POM functionally increased the phagocytic activity of macrophages. Based on our findings, POM is a promising therapeutic agent for CNS lymphoma with excellent CNS penetration, significant preclinical therapeutic activity, and a major impact on the tumor microenvironment. It can induce significant biological changes in tumor-associated macrophages, which likely play a major role in its therapeutic activity against CNS lymphoma. POM should be further evaluated in clinical trials.
    PLoS ONE 08/2013; 8(8):e71754. · 3.53 Impact Factor
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    ABSTRACT: We set out to identify Stearoyl-CoA desaturase 1 (SCD1) as a novel molecular target in clear cell renal cell carcinoma (ccRCC) and examine its role in tumor cell growth and viability in vitro and in vivo independently as well as in combination with current U.S. Food and Drug Administration (FDA)-approved regimens. Patient normal and ccRCC tissue samples and cell lines were examined for SCD1 expression. Genetic knockdown models and targeted inhibition of SCD1 through use of a small molecule inhibitor, A939572, were analyzed for growth, apoptosis, and alterations in gene expression using gene array analysis. Therapeutic models of synergy were evaluated utilizing pharmacologic inhibition of SCD1 with the tyrosine kinase inhibitors (TKI) sunitinib and pazopanib, and the mTOR inhibitor temsirolimus. Our studies identify increased SCD1 expression in all stages of ccRCC. Both genetic knockdown and pharmacologic inhibition of SCD1 decreased tumor cell proliferation and induced apoptosis in vitro and in vivo. Upon gene array, quantitative real-time PCR, and protein analysis of A939572-treated or SCD1 lentiviral knockdown samples, induction of endoplasmic reticulum stress response signaling was observed, providing mechanistic insight for SCD1 activity in ccRCC. Furthermore, combinatorial application of A939572 with temsirolimus synergistically inhibited tumor growth in vitro and in vivo. Increased SCD1 expression supports ccRCC viability and therefore we propose it as a novel molecular target for therapy either independently or in combination with an mTOR inhibitor for patients whose disease cannot be remedied with surgical intervention, such as in cases of advanced or metastatic disease. Clin Cancer Res; 19(9); 2368-80. ©2013 AACR.
    Clinical Cancer Research 05/2013; 19(9):2368-80. · 8.19 Impact Factor
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    ABSTRACT: Purpose:A Phase 1 study was initiated to determine safety, potential effectiveness, and maximal tolerated dose and recommended phase 2 dose of efatutazone and paclitaxel in anaplastic thyroid cancer (ATC).Experimental Design:Patients received efatutazone (0.15, 0.3, or 0.5 mg) orally twice daily (BID) then paclitaxel every 3 weeks. Patient tolerance and outcomes were assessed, as were serum efatutazone pharmacokinetics.Results:Ten of 15 patients were women. Median age was 59 years. Seven received 0.15 mg efatutazone, six received 0.3 mg, and two received 0.5 mg. One patient receiving 0.3 mg efatutazone had a partial response from Day 69 to Day 175; seven attained stable disease. Median time to progression in patients receiving 0.15 mg efatutazone was 48 days, and 68 days in those receiving 0.3 mg; corresponding median survival was 98 vs. 138 days. Median peak efatutazone blood level was 8.6 ng/mL for 0.15 mg dosing vs. 22.0 ng/mL for 0.3 mg BID dosing.Ten patients had ≥ grade 3 CTCAE adverse events, with two (anemia, edema) related to efatutazone. Thirteen events of edema were reported in 8 patients, with 2 ≥ grade 3. Eight patients had ≥ one serious adverse event, with one (anemia) attributed to efatutazone, and one (anaphylactic reaction) related to paclitaxel. Maximal tolerated dose was not achieved.Angiopoietin-like 4 was induced by efatutazone in tissue biopsies of two patients.Conclusions:Efatutazone and paclitaxel in combination were safe, tolerated, and had biologic activity.
    The Journal of Clinical Endocrinology and Metabolism 04/2013; · 6.31 Impact Factor
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    ABSTRACT: Anaplastic thyroid cancer (ATC) has perhaps the worst prognosis of any cancer, with a median survival of only about 5 months regardless of stage. Pazopanib monotherapy has promising clinical activity in differentiated thyroid cancers (generally attributed to vascular endothelial growth factor receptor inhibition), yet has less effective single-agent activity in ATC. We now report that combining pazopanib with microtubule inhibitors such as paclitaxel produced heightened and synergistic antitumor effects in ATC cells and xenografts that were associated with potentiated mitotic catastrophe. We hypothesized that combined effects may reflect enhanced paclitaxel-induced cytotoxicity mediated by cell cycle regulatory kinase inhibition by pazopanib. Indeed, pazopanib potently inhibited aurora A, with pazopanib/paclitaxel synergy recapitulated by aurora A short hairpin RNA knockdown or by specific aurora A pharmacological inhibition. Pazopanib/paclitaxel synergy was reversed by aurora A knockdown. Moreover, aurora A (but not B or C) message and protein levels were significantly increased in patient ATCs, and durable benefit resulted from pilot clinical translation of pazopanib/paclitaxel therapy in a patient with metastatic ATC. Collectively, these results suggest that the pazopanib/paclitaxel combination is a promising candidate therapeutic approach in ATC and that aurora A may represent a potentially viable therapeutic molecular target in ATC.
    Science translational medicine 01/2013; 5(166):166ra3. · 14.41 Impact Factor
  • Urologic Oncology 01/2013; · 3.36 Impact Factor
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    ABSTRACT: Historically, metastatic renal cell carcinoma (mRCC) is more resistant to conventional cytotoxic chemotherapeutic agents than other solid tumors. Although significant progress has been made over the last decade with several novel therapeutics, these agents invariably go on to fail, largely due to either intrinsic or acquired resistance. To help overcome, or at least delay resistance, combinatorial therapies utilizing agents with disparate, and ideally complementary, mechanisms of actions are needed. In this report, we assess the novel combination of the mTOR inhibitor, temsirolimus, with the microtubule stabilizing drug ixabepilone in RCC. Our results demonstrate synergy in multiple cell lines of RCC and further evaluation of this combination is warranted in the clinical setting. Activation of the endoplasmic reticulum (ER) stress response pathway may in part explain the combinatorial synergy. We further propose that ER stress induced proteins may serve as early response biomarkers to combinatorial therapy in a clinical trial.
    American Journal of Cancer Research 01/2013; 3(4):390-401. · 3.97 Impact Factor
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    Gynecologic Oncology 12/2012; 127(3):680. · 3.69 Impact Factor
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    ABSTRACT: PRSS3/mesotrypsin is an atypical isoform of trypsin that has been associated with breast, lung, and pancreatic cancer cell malignancy. In analyses of open source transcriptional microarray data, we find that PRSS3 expression is upregulated in metastatic prostate cancer tissue, and that expression of PRSS3 in primary prostate tumors is prognostic of systemic progression following prostatectomy. Using a mouse orthotopic model with bioluminescent imaging, we show that PRSS3/mesotrypsin is critical for prostate cancer metastasis. Silencing of PRSS3 inhibits anchorage-independent growth of prostate cancer cells in soft agar assays, and suppresses invasiveness in Matrigel transwell assays and three-dimensional (3D) cell culture models. We further show that treatment with recombinant mesotrypsin directly promotes an invasive cellular phenotype in prostate cancer cells and find that these effects are specific and require the proteolytic activity of mesotrypsin, because neither cationic trypsin nor a mesotrypsin mutant lacking activity can drive the invasive phenotype. Finally, we show that a newly developed, potent inhibitor of mesotrypsin activity can suppress prostate cancer cell invasion to a similar extent as PRSS3 gene silencing. This study defines mesotrypsin as an important mediator of prostate cancer progression and metastasis, and suggests that inhibition of mesotrypsin activity may provide a novel modality for prostate cancer treatment. Mol Cancer Res; 10(12); 1555-66. ©2012 AACR.
    Molecular Cancer Research 12/2012; 10(12):1555-66. · 4.35 Impact Factor
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    ABSTRACT: Background / Purpose: Many thyroid cell lines have been identified as being either cross-contaminated or redundant. Due to this finding, there were few pre-clinical models left for follicular thyroid carcinoma (FTC) research. Our lab has now characterized four new FTC cell lines. Main conclusion: The new cell lines are short tandem DNA repeat (STR) matched back to its patient tissue of origin and screened for thyroid markers and mutations. The cell lines are then used to demonstrate antitumor synergy using a MEK and Akt inhibitor.
    American Thyroid Association (ATA) 82nd Annual Meeting 2012; 10/2012
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    ABSTRACT: Bendamustine is a novel bifunctional chemotherapeutic agent with activity against multiple cancers. There has been no definitive data on its capacity to penetrate the central nervous system. Our chemoinformatic screening predicted excellent CNS penetration, which was validated by in vivo pharmacokinetic analysis in mice. Bendamustine has 35% CNS penetration in our mouse model. Bendamustine should be further evaluated for use in treatment of primary and secondary CNS tumors.
    Medicinal Chemistry Communication 10/2012; 3:1526-1530. · 2.63 Impact Factor
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    ABSTRACT: Metastatic solid tumors are aggressive and mostly drug resistant, leading to few treatment options and poor prognosis as seen with clear cell renal cell carcinoma (ccRCC) and triple-negative breast cancer (TNBC). Therefore, the identification of new therapeutic regimes for the treatment of metastatic disease is desirable. ccRCC and TNBC cell lines were treated with the HDAC inhibitor romidepsin and the methyltransferase inhibitor decitabine, two epigenetic modifying drugs approved by the U.S. Food and Drug Administration for the treatment of various hematologic malignancies. Cell proliferation analysis, flow cytometry, quantitative PCR, and immunoblotting techniques were used to evaluate the antitumor synergy of this drug combination and identify the reexpression of epigenetically silenced tumor suppressor genes. Combinatorial treatment of metastatic TNBC and stage IV ccRCC cell lines with romidepsin/decitabine leads to synergistic inhibition of cell growth and induction of apoptosis above levels of individual drug treatments alone. Synergistic reexpression of the tumor suppressor gene secreted frizzled-related protein one (sFRP1) was observed in combinatorial drug-treated groups. Silencing sFRP1 (short hairpin RNA) before combinatorial drug treatment showed that sFRP1 mediates the growth inhibitory and apoptotic activity of combined romidepsin/decitabine. Furthermore, addition of recombinant sFRP1 to ccRCC or TNBC cells inhibits cell growth in a dose-dependent manner through the induction of apoptosis, identifying that epigenetic silencing of sFRP1 contributes to renal and breast cancer cell survival. Combinatorial treatment with romidepsin and decitabine in drug resistant tumors is a promising treatment strategy. Moreover, recombinant sFRP1 may be a novel therapeutic strategy for cancers with suppressed sFRP1 expression. Mol Cancer Ther; 11(10); 2105-15. ©2012 AACR.
    Molecular Cancer Therapeutics 07/2012; 11(10):2105-15. · 5.60 Impact Factor

Publication Stats

2k Citations
391.31 Total Impact Points

Institutions

  • 2012
    • Mayo Clinic - Rochester
      Rochester, Minnesota, United States
  • 2008–2012
    • Mayo Foundation for Medical Education and Research
      Rochester, Michigan, United States
  • 2011
    • University of Texas Health Science Center at San Antonio
      • Department of Cellular and Structural Biology
      San Antonio, TX, United States
  • 2009
    • Beth Israel Deaconess Medical Center
      • Department of Pathology
      Boston, Massachusetts, United States
  • 2007–2009
    • Mayo Clinic
      Jacksonville, Florida, United States
  • 1997–2009
    • University of Texas Medical Branch at Galveston
      • • Center for Biomedical Engineering
      • • Department of Internal Medicine
      • • Department of Obstetrics and Gynecology
      Galveston, TX, United States
  • 2004
    • University of North Carolina at Chapel Hill
      • Department of Obstetrics and Gynecology
      Chapel Hill, NC, United States