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Generation of neural crest cells and peripheral sensory neurons from human embryonic stem cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Peripheral somatic sensory neurons (PSNs) are responsible for the critical function of transmitting multiple modalities of information from the outside world, including heat, touch, and pain, as well as the position of muscles required for coordinated voluntary movement to the central nervous system. Many peripheral neuropathies exist, including hereditary neurodegeneration in Familial Dysautonomia, infections of PSNs by viruses such as Varicella zoster and damage to PSNs and/or their process resulting from other disease conditions such as diabetes. Understanding of the etiology of these diseases and development of tre...
Source: Cell Research - November 15, 2009 Category: Cytology Authors: Goldstein RS, Pomp O, Brokhman I, Ziegler L Tags: Methods Mol Biol Source Type: journals

Nicotine Enhances the Antiapoptotic Function of Mcl-1 through Phosphorylation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Lung cancer has a strong etiologic association with cigarette smoking. Nicotine, a major component in tobacco smoke, functions as a survival agonist that inhibits apoptosis following various stresses. However, the mechanism of action remains elusive. Mcl-1, a major antiapoptotic protein of the Bcl2 family, is extensively expressed in both small cell and non-small cell lung cancer cells, suggesting that Mcl-1 may be a therapeutic target of patients with lung cancer. Here, we found that nicotine induces Mcl-1 phosphorylation through activation of extracellular signal-regulated kinase 1/2 in association with increased che...
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Zhao J, Xin M, Wang T, Zhang Y, Deng X Tags: Mol Cancer Res Source Type: journals

Upregulation of MMP-2 by HMGA1 Promotes Transformation in Undifferentiated, Large-Cell Lung Cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Although lung cancer is the leading cause of cancer death worldwide, the precise molecular mechanisms that give rise to lung cancer are incompletely understood. Here, we show that HMGA1 is an important oncogene that drives transformation in undifferentiated, large-cell carcinoma. First, we show that the HMGA1 gene is overexpressed in lung cancer cell lines and primary human lung tumors. Forced overexpression of HMGA1 induces a transformed phenotype with anchorage-independent cell growth in cultured lung cells derived from normal tissue. Conversely, inhibiting HMGA1 expression blocks anchorage-independent cell growth in...
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Hillion J, Wood LJ, Mukherjee M, Bhattacharya R, Di Cello F, Kowalski J, Elbahloul O, Segal J, Poirier J, Rudin CM, Dhara S, Belton A, Joseph B, Zucker S, Resar LM Tags: Mol Cancer Res Source Type: journals

Critical Role of Endogenous Heme Oxygenase 1 as a Tuner of the Invasive Potential of Prostate Cancer Cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Prostate cancer (PCa) is the second leading cause of cancer-associated death in men. Inflammation has been recognized as a risk factor for this disease. Heme oxygenase 1 (HO-1), the inducible isoform of the rate-limiting enzyme in heme degradation, counteracts oxidative and inflammatory damage. Here, we investigated the regulated expression of HO-1 and its functional consequences in PCa. We studied the effect of genetic and pharmacologic disruption of HO-1 in the growth, invasion, and migration in androgen-sensitive (MDA PCa2b and LNCaP) and androgen-insensitive (PC3) PCa cell lines. Our results show that HO-1 levels a...
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Gueron G, De Siervi A, Ferrando M, Salierno M, De Luca P, Elguero B, Meiss R, Navone N, Vazquez ES Tags: Mol Cancer Res Source Type: journals

p34SEI-1 Inhibits Doxorubicin-Induced Senescence through a Pathway Mediated by Protein Kinase C-{delta} and c-Jun-NH2-Kinase 1 Activation in Human Breast Cancer MCF7 Cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we describe a novel function of the p34(SEI-1) protein, which is both an oncogenic protein and a positive regulator of the cell cycle. The p34(SEI-1) protein was found to inhibit doxorubicin-induced senescence. We investigated the molecular mechanisms of the inhibitory effect of p34(SEI-1) on senescence. First, we found that the activation of protein kinase C-delta (PKC-delta), which is cleaved into a 38 kDa active form from a 78 kDa pro-form, induced after doxorubicin treatment, was inhibited by p34(SEI-1). Furthermore, p34(SEI-1) induced the ubiquitination of PKC-delta. Yet, there is no interaction between...
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Lee SL, Hong SW, Shin JS, Kim JS, Ko SG, Hong NJ, Kim DJ, Lee WJ, Jin DH, Lee MS Tags: Mol Cancer Res Source Type: journals

Effect of Granulocyte/Macrophage Colony-Stimulating Factor on Vaccination with an Allogeneic Whole-Cell Melanoma Vaccine.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CONCLUSION: These data suggest that GM-CSF is not helpful as an immune adjuvant in this dose and schedule and raise concern that it may be harmful. Based on the discordant findings of an immune endpoint and clinical outcome, the use of such surrogate endpoints in selecting treatments for further evaluation must be done with a great deal of caution. (Clin Cancer Res 2009;15(22):7029-35). PMID: 19903777 [PubMed - as supplied by publisher] (Source: Cell Research)
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Faries MB, Hsueh EC, Ye X, Hoban M, Morton DL Tags: Clin Cancer Res Source Type: journals

Immunostimulation Versus Immunosuppression after Multiple Vaccinations: the Woes of Therapeutic Vaccine Development.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Three articles in this issue of Clinical Cancer Research show how multiple vaccinations can lead to immunosuppression. Moreover, two studies in patients show that granulocyte macrophage colony-stimulating factor (GM-CSF) as an adjuvant immunostimulant to different kind of vaccines can lead to adverse outcome in terms of relapse-free and overall survival. Modulation of regulatory T-cell activity may be required to overcome this outcome and may be crucial for the successful development of therapeutic vaccines. (Clin Cancer Res 2009;15(22):6745-7). PMID: 19903779 [PubMed - as supplied by publisher] (Source: Cell Research)
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Eggermont AM Tags: Clin Cancer Res Source Type: journals

Effect of Granulocyte/Macrophage Colony-Stimulating Factor on Circulating CD8+ and CD4+ T-Cell Responses to a Multipeptide Melanoma Vaccine: Outcome of a Multicenter Randomized Trial.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CONCLUSIONS: High immune response rates for this multipeptide vaccine were achieved, but CD8(+) and CD4(+) T-cell responses were lower when administered with GM-CSF. These data challenge the value of local GM-CSF as a vaccine adjuvant in humans. (Clin Cancer Res 2009;15(22):7036-44). PMID: 19903780 [PubMed - as supplied by publisher] (Source: Cell Research)
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Slingluff CL, Petroni GR, Olson WC, Smolkin ME, Ross MI, Haas NB, Grosh WW, Boisvert ME, Kirkwood JM, Chianese-Bullock KA Tags: Clin Cancer Res Source Type: journals

Partial CD4 Depletion Reduces Regulatory T Cells Induced by Multiple Vaccinations and Restores Therapeutic Efficacy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CONCLUSION: These results suggest that CD4+ T(reg) cells limit the efficacy of multiple vaccinations and that timed partial depletion of CD4+ T cells may reduce suppression and "tip-the-balance" in favor of therapeutic antitumor immunity. The recent failure of large phase III cancer vaccine clinical trials, wherein patients received multiple vaccines, underscores the potential clinical relevance of these findings. (Clin Cancer Res 2009;15(22):6881-90). PMID: 19903784 [PubMed - as supplied by publisher] (Source: Cell Research)
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Lacelle MG, Jensen SM, Fox BA Tags: Clin Cancer Res Source Type: journals

A Phase 1 Dose Escalation Study of the Safety and Pharmacokinetics of the Novel Proteasome Inhibitor Carfilzomib (PR-171) in Patients with Hematologic Malignancies.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CONCLUSION: This is the first clinical use of carfilzomib that shows tolerability and clinical activity in multiple hematologic malignancies using consecutive-day dosing. (Clin Cancer Res 2009;15(22):7085-91). PMID: 19903785 [PubMed - as supplied by publisher] (Source: Cell Research)
Source: Cell Research - November 10, 2009 Category: Cytology Authors: O'Connor OA, Stewart AK, Vallone M, Molineaux CJ, Kunkel LA, Gerecitano JF, Orlowski RZ Tags: Clin Cancer Res Source Type: journals

Deregulated GSK3{beta} Sustains Gastrointestinal Cancer Cells Survival by Modulating Human Telomerase Reverse Transcriptase and Telomerase.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CONCLUSION: The results indicate that deregulated GSK3beta sustains gastrointestinal cancer cells survival through modulation of hTERT and telomerase. (Clin Cancer Res 2009;15(22):6810-19). PMID: 19903789 [PubMed - as supplied by publisher] (Source: Cell Research)
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Mai W, Kawakami K, Shakoori A, Kyo S, Miyashita K, Yokoi K, Jin M, Shimasaki T, Motoo Y, Minamoto T Tags: Clin Cancer Res Source Type: journals

A Novel Toll-Like Receptor 9 Agonist Cooperates with Trastuzumab in Trastuzumab-Resistant Breast Tumors through Multiple Mechanisms of Action.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CONCLUSIONS: We showed a cooperative effect of IMO plus trastuzumab in trastuzumab-resistant breast cancers due to IMO direct antitumor and antiangiogenic activity and antibody-dependent cell-mediated cytotoxicity enhancement. Moreover, we provided first evidence of a toll-like receptor 9/HER interaction at membrane level as novel mechanism of action. Altogether, we propose IMO plus trastuzumab as an effective strategy in trastuzumab-resistant breast cancers. (Clin Cancer Res 2009;15(22):6921-30). PMID: 19903791 [PubMed - as supplied by publisher] (Source: Cell Research)
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Damiano V, Garofalo S, Rosa R, Bianco R, Caputo R, Gelardi T, Merola G, Racioppi L, Garbi C, Kandimalla ER, Agrawal S, Tortora G Tags: Clin Cancer Res Source Type: journals

Curcumin Potentiates the Antitumor Effects of Bacillus Calmette-Guerin against Bladder Cancer through the Downregulation of NF-{kappa}B and Upregulation of TRAIL Receptors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Although Bacillus Calmette-Guerin (BCG) intravesical therapy is a standard treatment for bladder cancer, eventual failure of response is a major problem. Treatments that can augment BCG therapy are urgently needed. We investigated whether curcumin, a component of Curcuma longa (also called turmeric), has potential to improve the current therapy using in vitro and in vivo MBT-2 murine tumor models. We found that curcumin potentiated BCG-induced apoptosis of human bladder cancer cells. BCG stimulated the release of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) from peripheral mononuclear neutrophils in ...
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Kamat AM, Tharakan ST, Sung B, Aggarwal BB Tags: Cancer Res Source Type: journals

Recognition and Killing of Brain Tumor Stem-Like Initiating Cells by CD8+ Cytolytic T Cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Solid tumors contain a subset of stem-like cells that are resistant to the cytotoxic effects of chemotherapy/radiotherapy, but their susceptibility to cytolytic T lymphocyte (CTL) effector mechanisms has not been well characterized. Using a panel of early-passage human brain tumor stem/initiating cell (BTSC) lines derived from high-grade gliomas, we show that BTSCs are subject to immunologic recognition and elimination by CD8(+) CTLs. Compared with serum-differentiated CD133(low) tumor cells and established glioma cell lines, BTSCs are equivalent with respect to expression levels of HLA class I and ICAM-1, similar in t...
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Brown CE, Starr R, Martinez C, Aguilar B, D'Apuzzo M, Todorov I, Shih CC, Badie B, Hudecek M, Riddell SR, Jensen MC Tags: Cancer Res Source Type: journals

MiR-15a and MiR-16 Control Bmi-1 Expression in Ovarian Cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this report, we identify two miRNAs, miR-15a and miR-16, that are underexpressed in ovarian cell lines and in primary ovarian tissues. We show that these miRNAs directly target the Bmi-1 3' untranslated region and significantly correlate with Bmi-1 protein levels in ovarian cancer patients and cell lines. Furthermore, Bmi-1 protein levels are downregulated in response to miR-15a or miR-16 expression and lead to significant reduction in ovarian cancer cell proliferation and clonal growth. These findings suggest the development of therapeutic strategies by restoring miR-15a and miR-16 expression in ovarian cancer and in o...
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Bhattacharya R, Nicoloso M, Arvizo R, Wang E, Cortez A, Rossi S, Calin GA, Mukherjee P Tags: Cancer Res Source Type: journals

Autophagy Is Activated by TGF-{beta} and Potentiates TGF-{beta}-Mediated Growth Inhibition in Human Hepatocellular Carcinoma Cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that regulates cell growth, differentiation, and apoptosis of various types of cells. Autophagy is emerging as a critical response of normal and cancer cells to environmental changes, but the relationship between TGF-beta signaling and autophagy has been poorly understood. Here, we showed that TGF-beta activates autophagy in human hepatocellular carcinoma cell lines. TGF-beta induced accumulation of autophagosomes and conversion of microtubule-associated protein 1 light chain 3 and enhanced the degradation rate of long-lived proteins. TGF-beta inc...
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Kiyono K, Suzuki HI, Matsuyama H, Morishita Y, Komuro A, Kano MR, Sugimoto K, Miyazono K Tags: Cancer Res Source Type: journals

Differential Enhancement of Breast Cancer Cell Motility and Metastasis by Helical and Kinase Domain Mutations of Class IA Phosphoinositide 3-Kinase.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Class IA (p85/p110) phosphoinositide 3-kinases play a major role in regulating cell growth, survival, and motility. Activating mutations in the p110alpha isoform of the class IA catalytic subunit (PIK3CA) are commonly found in human cancers. These mutations lead to increased proliferation and transformation in cultured cells, but their effects on cell motility and tumor metastasis have not been evaluated. We used lentiviral-mediated gene transfer and knockdown to produce stable MDA-MB-231 cells in which the endogenous human p110alpha is replaced with either wild-type bovine p110alpha or the two most common activating p...
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Pang H, Flinn R, Patsialou A, Wyckoff J, Roussos ET, Wu H, Pozzuto M, Goswami S, Condeelis JS, Bresnick AR, Segall JE, Backer JM Tags: Cancer Res Source Type: journals

Persistence of Betapapillomavirus Infections as a Risk Factor for Actinic Keratoses, Precursor to Cutaneous Squamous Cell Carcinoma.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, persistent betaPV infections in this population were associated with an increased occurrence of actinic keratosis. Additional studies are needed to determine the possible association of betaPV persistence with SCC. [Cancer Res 2009;69(23):OF1-6]. PMID: 19903846 [PubMed - as supplied by publisher] (Source: Cell Research)
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Plasmeijer EI, Neale RE, de Koning MN, Quint WG, McBride P, Feltkamp MC, Green AC Tags: Cancer Res Source Type: journals

Estradiol Alters Cell Growth in Nonmalignant Colonocytes and Reduces the Formation of Preneoplastic Lesions in the Colon.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Numerous clinical and animal studies show that hormone replacement therapy reduces the risk of colon tumor formation. However, the majority of experiments have shown that estradiol (E(2)) does not inhibit the growth of malignantly transformed colon epithelia. As such, the presented studies focused on evaluating the effects of E(2) in noncancerous colonocytes. E(2) treatments (0-10 nmol/L) reduced cell growth and increased apoptotic activity in young adult mouse colonocytes (YAMC), a nonmalignant cell line, in a dose-responsive manner. These effects were lost in the YAMC-Ras cells, an isogenic cell line with a single ma...
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Weige CC, Allred KF, Allred CD Tags: Cancer Res Source Type: journals

Tangeretin Sensitizes Cisplatin-Resistant Human Ovarian Cancer Cells through Downregulation of Phosphoinositide 3-Kinase/Akt Signaling Pathway.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Combination of innocuous dietary components with anticancer drugs is an emerging new strategy for cancer chemotherapy to increase antitumor responses. Tangeretin is a citrus flavonoid known to inhibit cancer cell proliferation. Here, we show an enhanced response of A2780/CP70 and 2008/C13 cisplatin-resistant human ovarian cancer cells to various combination treatments of cisplatin and tangeretin. Pretreatment of cells with tangeretin before cisplatin treatment synergistically inhibited cancer cell proliferation. This combination was effective in activating apoptosis via caspase cascade as well as arresting cell cycle a...
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Arafa ES, Zhu Q, Barakat BM, Wani G, Zhao Q, El-Mahdy MA, Wani AA Tags: Cancer Res Source Type: journals

Detection of Treatment-Induced Changes in Signaling Pathways in Gastrointestinal Stromal Tumors Using Transcriptomic Data.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cell signaling plays a central role in the etiology of cancer. Numerous therapeutics in use or under development target signaling proteins; however, off-target effects often limit assignment of positive clinical response to the intended target. As direct measurements of signaling protein activity are not generally feasible during treatment, there is a need for more powerful methods to determine if therapeutics inhibit their targets and when off-target effects occur. We have used the Bayesian Decomposition algorithm and data on transcriptional regulation to create a novel methodology, Differential Expression for Signali...
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Ochs MF, Rink L, Tarn C, Mburu S, Taguchi T, Eisenberg B, Godwin AK Tags: Cancer Res Source Type: journals

Optimized Peptide Vaccines Eliciting Extensive CD8 T-Cell Responses with Therapeutic Antitumor Effects.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A major challenge for developing effective therapeutic vaccines against cancer is overcoming immunologic tolerance to tumor-associated antigens that are expressed on both malignant cells and normal tissues. Herein, we describe a novel vaccination approach, TriVax, that uses synthetic peptides representing CD8 T-cell epitopes, Toll-like receptor agonists that function as potent immunologic adjuvants and costimulatory anti-CD40 antibodies to generate large numbers of high-avidity antigen-reactive T cells capable of recognizing and killing tumor cells. Our results show that TriVax induced huge numbers of long-lasting anti...
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Cho HI, Celis E Tags: Cancer Res Source Type: journals

Improved Expression and Reactivity of Transduced Tumor-Specific TCRs in Human Lymphocytes by Specific Silencing of Endogenous TCR.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we developed retroviral vectors encoding both small interfering RNA constructs that specifically down-regulate endogenous TCR and a codon-optimized, small interfering RNA-resistant TCR specific for the human tumor antigens MAGE-A4 or WT1. At low copy numbers of the integrated vector, the transduced human lymphocytes exhibited high surface expression of the introduced tumor-specific TCR and reduced expression of endogenous TCRs. In consequence, the vector-transduced lymphocytes showed enhanced cytotoxic activity against antigen-expressing tumor cells. Therefore, our novel TCR gene therapy may open a new gate ...
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Okamoto S, Mineno J, Ikeda H, Fujiwara H, Yasukawa M, Shiku H, Kato I Tags: Cancer Res Source Type: journals

Astrocyte Elevated Gene-1: Far More Than Just a Gene Regulated in Astrocytes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Since its original cloning by subtraction hybridization in 2002, it is now evident that Astrocyte elevated gene-1 (AEG-1) is a key contributor to the carcinogenic process in diverse organs. AEG-1 protein expression is elevated in advanced stages of many cancers, which correlates with poor survival. In specific cancers, such as breast and liver cancer, the AEG-1 gene itself is amplified, further supporting a seminal role in tumorigenesis. Overexpression and inhibition studies both in in vitro and in in vivo models reveal the importance of AEG-1 in regulating multiple physiologically and pathologically relevant processes...
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Sarkar D, Emdad L, Lee SG, Yoo BK, Su ZZ, Fisher PB Tags: Cancer Res Source Type: journals

The Fibroblast Growth Factor Receptor Inhibitor PD173074 Blocks Small Cell Lung Cancer Growth In vitro and In vivo.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Lung cancer is the commonest cancer killer. Small cell lung cancer (SCLC) is initially chemosensitive, but rapidly relapses in a chemoresistant form with an overall survival of <5%. Consequently, novel therapies are urgently required and will likely arise from an improved understanding of the disease biology. Our previous work showed that fibroblast growth factor-2 induces proliferation and chemoresistance in SCLC cells. Here, we show that the selective fibroblast growth factor receptor (FGFR) inhibitor PD173074 blocks H-510 and H-69 SCLC proliferation and clonogenic growth in a dose-dependent fashion and prevents F...
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Pardo OE, Latigo J, Jeffery RE, Nye E, Poulsom R, Spencer-Dene B, Lemoine NR, Stamp GW, Aboagye EO, Seckl MJ Tags: Cancer Res Source Type: journals

Loss of Collapsin Response Mediator Protein1, as Detected by iTRAQ Analysis, Promotes Invasion of Human Gliomas Expressing Mutant EGFRvIII.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Glioblastoma multiforme (GBM) is the most common and lethal primary human brain tumor. GBMs are characterized by a variety of genetic alterations, among which oncogenic mutations of epidermal growth factor receptor (EGFRvIII) is most common. GBMs harboring EGFRvIII have increased proliferation and invasive characteristics versus those expressing wild-type (wt) EGFR. To identify the molecular basis of this increased tumorgenic phenotype, we used iTRAQ-labeling differential proteomic analysis. Among several differentially expressed proteins, we selected CRMP1, a protein implicated in cellular invasion that was markedly d...
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Mukherjee J, Desouza LV, Micallef J, Karim Z, Croul S, Siu KW, Guha A Tags: Cancer Res Source Type: journals

Targeted Disruption of the S1P2 Sphingosine 1-Phosphate Receptor Gene Leads to Diffuse Large B-Cell Lymphoma Formation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
S1P(2) sphingosine 1-phosphate receptor signaling can regulate proliferation, survival, morphology, and migration in many cell types in vitro. Here, we report that S1P(2)(-/-) mice develop clonal B-cell lymphomas with age, such that approximately half of the animals display this neoplasm by 1.5 to 2 years of age. Histologic, immunophenotypic, and molecular analyses revealed a uniform tumor phenotype with features of germinal center (GC)-derived diffuse large B-cell lymphoma (DLBCL). Tumor formation was preceded by increases in GC B cells and CD69(+) T cells, as well as an increased formation of spontaneous GCs, suggest...
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Cattoretti G, Mandelbaum J, Lee N, Chaves AH, Mahler AM, Chadburn A, Dalla-Favera R, Pasqualucci L, Maclennan AJ Tags: Cancer Res Source Type: journals

De-N-acetyl GM3 Promotes Melanoma Cell Migration and Invasion through Urokinase Plasminogen Activator Receptor Signaling-Dependent MMP-2 Activation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We have recently discovered that de-N-acetyl GM3 [NeuNH(2)LacCer, d-GM3], a derivative of ganglioside GM3, is specifically expressed in metastatic tumor cells and that its expression correlates with an enhanced metastatic phenotype. Although the classic N-acetylated form of GM3 (NeuAcLacCer, c-GM3) is found in both normal and tumor cells, metastatic tumor cells (but not other cells) predominantly express d-GM3 (82-95% of total GM3). d-GM3 expression is mainly found in metastatic melanomas, but not in benign nevi or the majority of primary melanomas. Using metastatic (d-GM3-positive) and poorly invasive (d-GM3-negative)...
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Liu JW, Sun P, Yan Q, Paller AS, Gerami P, Ho N, Vashi N, Le Poole IC, Wang XQ Tags: Cancer Res Source Type: journals

Improved biological performance of microarc-oxidized low-modulus Ti-24Nb-4Zr-7.9Sn alloy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Ti-24Nb-4Zr-7.9Sn (TNZS) is a newly developed beta-titanium alloy with low modulus and it has been considered as good material for dental or orthopedic implant. The purpose of the current study is to evaluate the effect of micro-arc oxidation (MAO) treatment on the biological performance of TNZS surface. The phases, morphology and chemical composition of the MAO-treated surface were characterized by X-ray diffraction, energy dispersive spectroscope and scanning electron microscopy analysis respectively. Then we tested the biocompatibility by examining the cell morphology and viability of osteoblast cells growing on MAO...
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Wu J, Liu ZM, Zhao XH, Gao Y, Hu J, Gao B Tags: J Biomed Mater Res B Appl Biomater Source Type: journals

Synthesis and characterization of functionalized magnetic maghemite nanoparticles with fluorescent probe capabilities for biological applications.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study describes new magnetic nanoparticles (MNPs) containing the fluorescent dye rhodamine isothiocyanate (RITC) covalently encapsulated within the nanoparticles. These nanoparticles have been prepared by nucleation followed by controlled growth of iron oxide layers onto iron oxide/gelatin-RITC nuclei. The formed RITC labeled MNPs (R-MNPs) are of narrow size distribution, exhibit the fluorescent spectrum of RITC, yet are more photostable. Because of the covalent encapsulation of RITC within the MNPs no detectable leakage of the fluorescent dye into the aqueous continuous phase was observed. This manuscript also demons...
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Perlstein B, Lublin-Tennenbaum T, Marom I, Margel S Tags: J Biomed Mater Res B Appl Biomater Source Type: journals

The mechanical and biological properties of an injectable calcium phosphate cement-fibrin glue composite for bone regeneration.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The objective of this study was to investigate the effects of FG on the mechanical and biological properties of CPC in an injectable CPC-FG composite. The initial setting time of this CPC-FG was delayed compared with the CPC control at different powder/liquid (P/L) mass ratio (p > 0.05). At a P/L of 5, the strength was (38.41 +/- 4.32) MPa for the CPC-FG, much higher than (27.42 +/- 2.85) MPa for the CPC alone (p < 0.05). SEM showed bone marrow stromal cells (BMSCs) with healthy spreading and anchored on the CPC-FG composite. After 14 days, the alkaline phosphatase (ALP) activity was (538 +/- 33) for the BMSCs on the...
Source: Cell Research - November 10, 2009 Category: Cytology Authors: Cui G, Li J, Lei W, Bi L, Tang P, Liang Y, Tao S, Wang Y Tags: J Biomed Mater Res B Appl Biomater Source Type: journals

Modular behavior of tauD provides insight into the origin of specificity in {alpha}-ketoglutarate-dependent nonheme iron oxygenases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Taurine alpha-ketoglutarate dioxygenase (tauD) is one of the best-studied alpha-ketoglutarate (alphaKG)-dependent nonheme iron oxygenases. As with all oxygenases, a fine balance must be struck between generating a species sufficiently reactive for the required chemistry and controlling that species to prevent undesirable side reactions [Klinman JP (2007) Accts Chem Res 40:325-333]. In the case of tauD, the substrate oxidizing species has been shown to be a ferryl-oxo, and the introduction of deuterium at the reactive position of substrate results in an enormous kinetic isotope effect together with a partial uncoupling ...
Source: Cell Research - November 5, 2009 Category: Cytology Authors: McCusker KP, Klinman JP Tags: Proc Natl Acad Sci U S A Source Type: journals

Engineering scaffold-free bone tissue using bone marrow stromal cell sheets.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The use of exogenous scaffolds to engineer bone tissue faces several drawbacks including insufficient biological activity, potential immunogenicity, elevated inflammatory reaction, fluctuating degradation rate, and low cell-attachment efficiency. To circumvent these limitations, we sought to engineer large scaffold-free bone tissue using cell sheets. We harvested intact cell sheets from bone marrow stromal cells using a continuous culture method and a scraping technique. The cell sheets were then rolled and fabricated into large constructs. Finally, the constructs were implanted into the subcutaneous pockets of nude mi...
Source: Cell Research - November 4, 2009 Category: Cytology Authors: Ma D, Ren L, Liu Y, Chen F, Zhang J, Xue Z, Mao T Tags: J Orthop Res Source Type: journals

The effect of skeletal maturity on the regenerative function of intrinsic ACL cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we hypothesized that fibroblastic cells from the ACLs of skeletally immature animals would proliferate and migrate more quickly than cells from adolescent and adult animals. ACL tissue from skeletally immature, adolescent, and adult pigs and sheep were obtained and cells obtained using explant culture. Cell proliferation within a collagen-platelet scaffold was measured at days 2, 7, and 14 of culture using AM MTT assay. Cellular migration was measured at 4 and 24 h using a modified Boyden chamber assay, and cell outgrowth from the explants also measured at 1 week. ACL cells from skeletally immature animals h...
Source: Cell Research - November 4, 2009 Category: Cytology Authors: Mastrangelo AN, Magarian EM, Palmer MP, Vavken P, Murray MM Tags: J Orthop Res Source Type: journals

Role of Class 3 Semaphorins and Their Receptors in Tumor Growth and Angiogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Class 3 semaphorins (SEMA3) were first identified as glycoproteins that negatively mediate neuronal guidance by binding to neuropilin and repelling neurons away from the source of SEMA3. However, studies have shown that SEMA3s are also secreted by other cell types, including tumor cells, where they play an inhibitory role in tumor growth and angiogenesis (specifically SEMA3B and SEMA3F). SEMA3s primarily inhibit the cell motility and migration of tumor and endothelial cells by inducing collapse of the actin cytoskeleton via neuropilins and plexins. Besides binding to SEMA3s, neuropilin also binds the protumorigenic and...
Source: Cell Research - November 3, 2009 Category: Cytology Authors: Gaur P, Bielenberg DR, Samuel S, Bose D, Zhou Y, Gray MJ, Dallas NA, Fan F, Xia L, Lu J, Ellis LM Tags: Clin Cancer Res Source Type: journals

Snail Promotes CXCR2 Ligand-Dependent Tumor Progression in Non-Small Cell Lung Carcinoma.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CONCLUSION: Snail upregulation plays a role in human NSCLC by promoting tumor progression mediated by CXCR2 ligands. (Clin Cancer Res 2009;15(22):6820-9). PMID: 19887480 [PubMed - as supplied by publisher] (Source: Cell Research)
Source: Cell Research - November 3, 2009 Category: Cytology Authors: Yanagawa J, Walser TC, Zhu LX, Hong L, Fishbein MC, Mah V, Chia D, Goodglick L, Elashoff DA, Luo J, Magyar CE, Dohadwala M, Lee JM, St John MA, Strieter RM, Sharma S, Dubinett SM Tags: Clin Cancer Res Source Type: journals

Production of Interferon-{gamma}-Inducible Protein-10 and Its Role as an Autocrine Invasion Factor in Nasal Natural Killer/T-Cell Lymphoma Cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CONCLUSIONS: These results suggest that IP-10 may play an important role in cell invasion in nasal NK/T-cell lymphoma through an autocrine mechanism. (Clin Cancer Res 2009;15(22):6771-9). PMID: 19887486 [PubMed - as supplied by publisher] (Source: Cell Research)
Source: Cell Research - November 3, 2009 Category: Cytology Authors: Moriai S, Takahara M, Ogino T, Nagato T, Kishibe K, Ishii H, Katayama A, Shimizu N, Harabuchi Y Tags: Clin Cancer Res Source Type: journals

Circulating Tumor Cell as a Diagnostic Marker in Primary Lung Cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CONCLUSIONS: CTC is a useful surrogate marker of distant metastasis in primary lung cancer. (Clin Cancer Res 2009;15(22):6980-6). PMID: 19887487 [PubMed - as supplied by publisher] (Source: Cell Research)
Source: Cell Research - November 3, 2009 Category: Cytology Authors: Tanaka F, Yoneda K, Kondo N, Hashimoto M, Takuwa T, Matsumoto S, Okumura Y, Rahman S, Tsubota N, Tsujimura T, Kuribayashi K, Fukuoka K, Nakano T, Hasegawa S Tags: Clin Cancer Res Source Type: journals

Combined Inhibition of Janus Kinase 1/2 for the Treatment of JAK2V617F-Driven Neoplasms: Selective Effects on Mutant Cells and Improvements in Measures of Disease Severity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CONCLUSIONS: These data showed that administration of the dual JAK1/2 inhibitor INCB16562 reduces malignant cell burden, normalizes spleen size and architecture, suppresses inflammatory cytokines, improves weight gain, and extends survival in a rodent model of JAK2V617F-driven hematologic malignancy. Thus, selective inhibitors of JAK1 and JAK2 represent a novel therapy for the patients with myeloproliferative diseases and other neoplasms associated with JAK dysregulation. (Clin Cancer Res 2009;15(22):6891-900). PMID: 19887489 [PubMed - as supplied by publisher] (Source: Cell Research)
Source: Cell Research - November 3, 2009 Category: Cytology Authors: Liu PC, Caulder E, Li J, Waeltz P, Margulis A, Wynn R, Becker-Pasha M, Li Y, Crowgey E, Hollis G, Haley P, Sparks RB, Combs AP, Rodgers JD, Burn TC, Vaddi K, Fridman JS Tags: Clin Cancer Res Source Type: journals

Lysine 63 Polyubiquitination in Immunotherapy and in Cancer-promoting Inflammation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Covalent and reversible post-translational modifications of proteins are a common theme in signaling. Ubiquitin conjugation was originally described to target proteins to proteasomal degradation by ubiquitin polymerization involving lysine (K) 48 residues. Differently linked polymers of polyubiquitin have been found that modify proteins without targeting to proteasomal degradation. Instead this pathway creates docking sites for signaling scaffolds that are key to control the nuclear factor-kappaB (NF-kappaB) pathway. Indeed TRAF-2, TRAF-6, and TRAF-3 are E3 ubiquitin ligases that form K63-linked ubiquitin polymers. The...
Source: Cell Research - November 3, 2009 Category: Cytology Authors: Martinez-Forero I, Rouzaut A, Palazon A, Dubrot J, Melero I Tags: Clin Cancer Res Source Type: journals

Fibulin-3 Is Uniquely Upregulated in Malignant Gliomas and Promotes Tumor Cell Motility and Invasion.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Malignant gliomas are highly invasive tumors with an almost invariably rapid and lethal outcome. Surgery and chemoradiotherapy fail to remove resistant tumor cells that disperse within normal tissue, which are a major cause for disease progression and therapy failure. Infiltration of the neural parenchyma is a distinctive property of malignant gliomas compared with other solid tumors. Thus, glioma cells are thought to produce unique molecular changes that remodel the neural extracellular matrix and form a microenvironment permissive for their motility. Here, we describe the unique expression and proinvasive role of fib...
Source: Cell Research - November 3, 2009 Category: Cytology Authors: Hu B, Thirtamara-Rajamani KK, Sim H, Viapiano MS Tags: Mol Cancer Res Source Type: journals

The Alkylphospholipid Perifosine Induces Apoptosis and p21-Mediated Cell Cycle Arrest in Medulloblastoma.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Medulloblastoma is the most common malignant cancer of the central nervous system in children. AKT kinases are part of a survival pathway that has been found to be significantly elevated in medulloblastoma. This pathway is a point of convergence for many growth factors and controls cellular processes that are critical for tumor cell survival and proliferation. The alkyl-phospholipid perifosine [octadecyl-(1,1-dimethyl-4-piperidylio) phosphate] is a small molecule inhibitor in clinical trials in peripheral cancers which acts as a competitive inhibitor of AKT kinases. Medulloblastoma cell cultures were used to study the ...
Source: Cell Research - November 3, 2009 Category: Cytology Authors: Kumar A, Fillmore HL, Kadian R, Broaddus WC, Tye GW, Van Meter TE Tags: Mol Cancer Res Source Type: journals

Toll-like Receptors 3 and 7 Agonists Enhance Tumor Cell Lysis by Human {gamma}{delta} T Cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We examined TLR3- and TLR7-expressing pancreatic adenocarcinomas, squamous cell carcinomas of head and neck and lung carcinomas. Poly(I:C) treatment of pancreatic adenocarcinomas followed by coculture with gammadelta T cells resulted in an upregulation of CD54 on the tumor cells. The interaction of CD54 and the corresponding ligand CD11a/CD18 expressed on gammadelta T cells is responsible for triggering effector function in gammadelta T cells. Moreover, treatment with imiquimod downregulated MHC class I molecules on tumor cells possibly resulting in a reduced binding affinity for inhibitory receptor NKG2A expressed on gamm...
Source: Cell Research - November 3, 2009 Category: Cytology Authors: Shojaei H, Oberg HH, Juricke M, Marischen L, Kunz M, Mundhenke C, Gieseler F, Kabelitz D, Wesch D Tags: Cancer Res Source Type: journals

{beta}1-Integrin Circumvents the Antiproliferative Effects of Trastuzumab in Human Epidermal Growth Factor Receptor-2-Positive Breast Cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Resistance to trastuzumab, the monoclonal antibody targeting human epidermal growth factor receptor 2 (HER-2), is a major concern for HER-2-positive metastatic breast cancer (MBC) patients. To date, HER-2 status is the only available biomarker for selecting patients for trastuzumab-based therapy. beta(1)-Integrin, an adhesion molecule involved in cell survival and drug resistance, shares common downstream signaling elements with HER-2, such as the phosphatidylinositol 3-kinase/Akt and extracellular signal-regulated kinase-1/2 (ERK1/2) pathways. The significance of beta(1)-integrin expression in HER-2-positive breast ca...
Source: Cell Research - November 3, 2009 Category: Cytology Authors: Lesniak D, Xu Y, Deschenes J, Lai R, Thoms J, Murray D, Gosh S, Mackey JR, Sabri S, Abdulkarim B Tags: Cancer Res Source Type: journals

Motor Protein-Dependent Membrane Trafficking of KCl Cotransporter-4 Is Important for Cancer Cell Invasion.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study stresses the important role of KCC4 in tumor malignant behavior. Real-time reverse transcription-PCR on samples collected by laser microdissection and immunofluorescent stainings with different KCC isoform antibodies indicate that KCC4 is abundant in metastatic cervical and ovarian cancer tissues. Insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF) stimulate KCC4 recruitment from a presumably inactive cytoplasmic pool of endoplasmic reticulum and Golgi to plasma membrane along actin cytoskeleton that is significantly inhibited by LY294002 and wortmannin. Throughout the trafficking process, KCC...
Source: Cell Research - November 3, 2009 Category: Cytology Authors: Chen YF, Chou CY, Wilkins RJ, Ellory JC, Mount DB, Shen MR Tags: Cancer Res Source Type: journals

Lin-Sca-1+CD49fhigh Stem/Progenitors Are Tumor-Initiating Cells in the Pten-Null Prostate Cancer Model.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We have shown previously that Pten deletion leads to the expansion of subset of prostate cancer cells positive for CK5 and p63. Although this subpopulation may be involved in tumor initiation or progression, studies to date have not functionally validated this hypothesis. Using in vitro sphere-forming assay and in vivo prostate reconstitution assay, we show here the presence of a tumor-initiating subpopulation in the Pten prostate cancer mouse model. Specifically, we show that the Lin(-)Sca-1(+)CD49f(high) (LSC) subpopulation overlaps with CK5(+);p63(+) cells and is significantly increased during prostate cancer initia...
Source: Cell Research - November 3, 2009 Category: Cytology Authors: Mulholland DJ, Xin L, Morim A, Lawson D, Witte O, Wu H Tags: Cancer Res Source Type: journals

Functional Significance of Wnt Inhibitory Factor-1 Gene in Kidney Cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, this is the first report documenting that the WIF-1 is downregulated by promoter methylation and functions as a tumor suppressor gene by inducing apoptosis in RCC cells. [Cancer Res 2009;69(22):8603-10]. PMID: 19887605 [PubMed - as supplied by publisher] (Source: Cell Research)
Source: Cell Research - November 3, 2009 Category: Cytology Authors: Kawakami K, Hirata H, Yamamura S, Kikuno N, Saini S, Majid S, Tanaka Y, Kawamoto K, Enokida H, Nakagawa M, Dahiya R Tags: Cancer Res Source Type: journals

TP53 Cancerous Mutations Exhibit Selection for Translation Efficiency.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The tumor suppressor gene TP53 is known to be a key regulator in cancer, and more than half of human cancers exhibit mutations in this gene. Recent evidence shows that point mutations in TP53 not only disrupt its function but also possess gain-of-function and dominant-negative effects on wild-type copies, thus making the mutated gene an oncogene. Hence, this brings about the possibility that TP53 mutations may be under selection for increasing the overall translation efficiency (TE) of defected TP53 in cancerous cells. Here, we perform the first large-scale analysis of TE in human cancer mutated TP53 variants, identify...
Source: Cell Research - November 3, 2009 Category: Cytology Authors: Waldman YY, Tuller T, Sharan R, Ruppin E Tags: Cancer Res Source Type: journals

NPM-ALK Oncogenic Tyrosine Kinase Controls T-Cell Identity by Transcriptional Regulation and Epigenetic Silencing in Lymphoma Cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Transformed cells in lymphomas usually maintain the phenotype of the postulated normal lymphocyte from which they arise. By contrast, anaplastic large cell lymphoma (ALCL) is a T-cell lymphoma with aberrant phenotype because of the defective expression of the T-cell receptor and other T-cell-specific molecules for still undetermined mechanisms. The majority of ALCL carries the translocation t(2;5) that encodes for the oncogenic tyrosine kinase NPM-ALK, fundamental for survival, proliferation, and migration of transformed T cells. Here, we show that loss of T-cell-specific molecules in ALCL cases is broader than reporte...
Source: Cell Research - November 3, 2009 Category: Cytology Authors: Ambrogio C, Martinengo C, Voena C, Tondat F, Riera L, di Celle PF, Inghirami G, Chiarle R Tags: Cancer Res Source Type: journals

A Novel Role of Interleukin-13 Receptor {alpha}2 in Pancreatic Cancer Invasion and Metastasis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Whereas interleukin-13 receptor alpha2 chain (IL-13Ralpha2) is overexpressed in a variety of human solid cancers including pancreatic cancer, we investigated its significance in cancer invasion and metastasis. We used two pancreatic cancer cell lines, IL-13Ralpha2-negative HPAF-II and IL-13Ralpha2-positive HS766T, and generated IL-13Ralpha2 stably transfected HPAF-II as well as IL-13Ralpha2 RNA interference knocked-down HS766T cells. Ability of invasion and signal transduction was compared between IL-13Ralpha2-negative and IL-13Ralpha2-positive cells and tumor metastasis was assessed in murine model for human pancreati...
Source: Cell Research - November 3, 2009 Category: Cytology Authors: Fujisawa T, Joshi B, Nakajima A, Puri RK Tags: Cancer Res Source Type: journals