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Melanoma HELP
Based on 32,740 articles published since 2009
|||| 32,740 

These are the 16 published retractions about Melanoma that originated from Worldwide during 2009-2019.
+ Citations + Abstracts
1 Retraction FMN2 Makes Perinuclear Actin to Protect Nuclei during Confined Migration and Promote Metastasis. 2016

Skau, Colleen T / Fischer, Robert S / Gurel, Pinar / Thiam, Hawa Racine / Tubbs, Anthony / Baird, Michelle A / Davidson, Michael W / Piel, Matthieu / Alushin, Gregory M / Nussenzweig, Andre / Steeg, Patricia S / Waterman, Clare M. ·Cell Biology and Physiology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. · Cell Biology and Physiology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA; Institut Curie, CNRS UMR 144, 26 rue d'Ulm, 75005 Paris, France. · Laboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. · Cell Biology and Physiology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA; Magnet Lab, Florida State University, Tallahassee, FL 32306, USA. · Magnet Lab, Florida State University, Tallahassee, FL 32306, USA. · Institut Curie, CNRS UMR 144, 26 rue d'Ulm, 75005 Paris, France. · Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. · Cell Biology and Physiology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: watermancm@nhlbi.nih.gov. ·Cell · Pubmed #27839864.

ABSTRACT: Cell migration in confined 3D tissue microenvironments is critical for both normal physiological functions and dissemination of tumor cells. We discovered a cytoskeletal structure that prevents damage to the nucleus during migration in confined microenvironments. The formin-family actin filament nucleator FMN2 associates with and generates a perinuclear actin/focal adhesion (FA) system that is distinct from previously characterized actin/FA structures. This system controls nuclear shape and positioning in cells migrating on 2D surfaces. In confined 3D microenvironments, FMN2 promotes cell survival by limiting nuclear envelope damage and DNA double-strand breaks. We found that FMN2 is upregulated in human melanomas and showed that disruption of FMN2 in mouse melanoma cells inhibits their extravasation and metastasis to the lung. Our results indicate a critical role for FMN2 in generating a perinuclear actin/FA system that protects the nucleus and DNA from damage to promote cell survival during confined migration and thus promote cancer metastasis.

2 Retraction MDA-9/syntenin is essential for factor VIIa-induced signaling, migration, and metastasis in melanoma cells. 2015

Aissaoui, Hanaa / Prévost, Célia / Boucharaba, Ahmed / Sanhadji, Kamel / Bordet, Jean-Claude / Négrier, Claude / Boukerche, Habib. ·From the EA 4174, Onco-Hematology Unit, University Claude Bernard, INSERM, Lyon 1, 69372 Lyon, France. · the Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland, and. · the Transplantation and Clinical Immunology Department, Edouart Herriot Hospital, Lyon, France. · From the EA 4174, Onco-Hematology Unit, University Claude Bernard, INSERM, Lyon 1, 69372 Lyon, France, habib.boukerche@univ-lyon1.fr. ·J Biol Chem · Pubmed #25505176.

ABSTRACT: Melanoma differentiation associated gene-9 (MDA-9), also known as syntenin, is a novel gene that positively regulates cancer cell motility, invasion, and metastasis through distinct biochemical and signaling pathways, but how MDA-9/syntenin is regulated in response to signals with the extracellular environment and promotes tumor progression is unclear. We now demonstrate that MDA-9/syntenin is dramatically up-regulated by a combination of rFVIIa and factor F(X) in malignant melanoma. Induction of MDA-9/syntenin in melanoma was found to occur in a thrombin-independent signaling pathway and involves the PAR-1/c-Src/Rho GTPases Rac1 and Cdc42/c-Jun N-terminal kinase axis resulting in the activation of paxillin, NF-κB, and matrix metalloproteinase-2 (MMP-2). MDA-9/syntenin physically interacts with c-Src through its PDZ binding motif following stimulation of melanoma cells with rFVIIa and FX. We also document that induction of this signaling pathway is required for TF·FVIIa·Xa-induced cell migration, invasion, and metastasis by melanoma cells. The present finding uncovers a novel role of MDA-9/syntenin as an important TF·FVIIa·Xa/PAR-1-regulated gene that initiates a signaling circuit essential for cell motility and invasion of metastatic melanoma. In these contexts, targeting TF·FVIIa·Xa and its relevant downstream targets such as MDA-9/syntenin, may represent a novel therapeutic strategy to control the evolution of neoplastic cells.

3 Retraction MicroRNA-143 targets Syndecan-1 to repress cell growth in melanoma. 2014

Li, Ruiya / Zhang, Lingli / Jia, Lizhou / Duan, Yan / Li, Yan / Wang, Jie / Bao, Lidao / Sha, Na. ·Department of Dermatology, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia Autonomous Region, China. · Department of Pathology, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia Autonomous Region, China. · Department of Pathology, The Affiliated People's Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China. · Department of Dermatology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China. · Department of Pharmacy, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China. ·PLoS One · Pubmed #24722758.

ABSTRACT: Melanoma is the most aggressive type of skin cancer with a rapid progression and a limited efficiency of therapeutics. Recently, studies have identified some microRNAs playing important roles in the development of melanoma. Syndecan-1 (Syn-1), dysregulated in many cancers, plays important roles in tumor progression by controlling cell proliferation. In this study, we investigated whether microRNA-143 (miR-143) is involved in the regulation of Syn-1 and thus plays a functional role in melanoma. We found that miR-143 expression was significantly lower in melanoma tissues than in normal tissues and its low expression was closely related to clinical stages of melanoma. Further experiments showed that consistent with the inhibitory effects induced by knockdown of Syn-1, overexpression of miR-143 suppressed cell proliferation, promoted G1 phase arrest and induced apoptosis in melanoma. Downregulation of miR-143 apparently produced opposite effects. Combined treatment of miR-143 overexpression and Syn-1 knockdown induced remarkable synergistic effects, while reconstitution of miR-143-resistant Syn-1 reversed the inhibitory activity of miR-143. Moreover, miR-143 level was inversely correlated with Syn-1 expression in melanoma cells. miR-143 directly targeted the 3'-untranslated regions of Syn-1 mRNA and they were in the same Argonaute2 complex. Taken together, this study revealed a link between miRNA-143 and Syn-1 in the pathogenesis of melanoma. MiR-143 plays an important role in the regulation of cell growth in melanoma. Restoration of miR-143 expression may represent a promising and efficient therapeutic approach for targeting malignant melanoma.

4 Retraction Comprehensive assessment of the association of ERCC2 Lys751Gln polymorphism with susceptibility to cutaneous melanoma. 2013

Dong, Yuhao / Zhuang, Le / Ma, Weiyuan. ·Shandong University School of Medicine, Jinan, 250012, China. ·Tumour Biol · Pubmed #23494240.

ABSTRACT: Previous studies evaluating the association between excision repair cross-complimentary group 2 (ERCC2) Lys751Gln polymorphism and susceptibility to cutaneous melanoma reported conflicting findings. We searched PubMed and Wangfang Medical databases up to October 16, 2012 to identify eligible studies. A total of 8 case-control studies including 3,492 cases and 5,381 controls were included in the meta-analysis. Statistical analysis was performed with Review Manage version 5.1. Odds ratios (ORs) with 95 % confidence intervals (95 %CIs) were used to assess the strength of the association. There was no obvious between-study heterogeneity among those eight studies under all four comparison models. Overall, there was a significant association between ERCC2 Lys751Gln polymorphism and susceptibility to cutaneous melanoma under three genetic models (for Gln versus Lys: OR = 1.08, 95 % CI = 1.01-1.15, P = 0.02; for GlnGln versus LysLys: OR = 1.16, 95 % CI = 1.01-1.33, P = 0.03; for GlnGln/LysGln versus LysLys: OR = 1.10, 95 % CI = 1.01-1.21, P = 0.04). Sensitivity analysis by omitting one study a time showed the significance of the pooled ORs was stable under all those three genetic models above. Therefore, the meta-analysis suggests that there is a significant association between ERCC2 Lys751Gln polymorphism and susceptibility to cutaneous melanoma.

5 Retraction High-avidity T cells are preferentially tolerized in the tumor microenvironment. 2013

Zhu, Ziqiang / Singh, Vinod / Watkins, Stephanie K / Bronte, Vincenzo / Shoe, Jennifer L / Feigenbaum, Lionel / Hurwitz, Arthur A. ·Tumor Immunity and Tolerance Section, Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Frederick National Laboratory for Cancer Research, NCI, Frederick, MD 21702, USA. ·Cancer Res · Pubmed #23204239.

ABSTRACT: One obstacle in eliciting potent antitumor immune responses is the induction of tolerance to tumor antigens. TCR(lo) mice bearing a TCR transgene specific for the melanoma antigen tyrosinase-related protein-2 (TRP-2, Dct) harbor T cells that maintain tumor antigen responsiveness but lack the ability to control melanoma outgrowth. We used this model to determine whether higher avidity T cells could control tumor growth without becoming tolerized. As a part of the current study, we developed a second TRP-2-specific TCR transgenic mouse line (TCR(hi)) that bears higher avidity T cells and spontaneously developed autoimmune depigmentation. In contrast to TCR(lo) T cells, which were ignorant of tumor-derived antigen, TCR(hi) T cells initially delayed subcutaneous B16 melanoma tumor growth. However, persistence in the tumor microenvironment resulted in reduced IFN-γ production and CD107a (Lamp1) mobilization, hallmarks of T-cell tolerization. IFN-γ expression by TCR(hi) T cells was critical for upregulation of MHC-I on tumor cells and control of tumor growth. Blockade of PD-1 signals prevented T-cell tolerization and restored tumor immunity. Depletion of tumor-associated dendritic cells (TADC) reduced tolerization of TCR(hi) T cells and enhanced their antitumor activity. In addition, TADCs tolerized TCR(hi) T cells but not TCR(lo) T cells in vitro. Our findings show that T-cell avidity is a critical determinant of not only tumor control but also susceptibility to tolerization in the tumor microenvironment. For this reason, care should be exercised when considering T-cell avidity in designing cancer immunotherapeutics.

6 Retraction Isolation of immune cells from primary tumors. 2012

Watkins, Stephanie K / Zhu, Ziqiang / Watkins, Keith E / Hurwitz, Arthur A. ·Tumor Immunity and Tolerance Section, Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, National Cancer Institute - Frederick, USA. ·J Vis Exp · Pubmed #22733225.

ABSTRACT: Tumors create a unique immunosuppressive microenvironment (tumor microenvironment, TME) whereby leukocytes are recruited into the tumor by various chemokines and growth factors. However, once in the TME, these cells lose the ability to promote anti-tumor immunity and begin to support tumor growth and down-regulate anti-tumor immune responses. Studies on tumor-associated leukocytes have mainly focused on cells isolated from tumor-draining lymph nodes or spleen due to the inherent difficulties in obtaining sufficient cell numbers and purity from the primary tumor. While identifying the mechanisms of cell activation and trafficking through the lymphatic system of tumor bearing mice is important and may give insight to the kinetics of immune responses to cancer, in our experience, many leukocytes, including dendritic cells (DCs), in tumor-draining lymph nodes have a different phenotype than those that infiltrate tumors. Furthermore, we have previously demonstrated that adoptively-transferred T cells isolated from the tumor-draining lymph nodes are not tolerized and are capable of responding to secondary stimulation in vitro unlike T cells isolated from the TME, which are tolerized and incapable of proliferation or cytokine production. Interestingly, we have shown that changing the tumor microenvironment, such as providing CD4(+) T helper cells via adoptive transfer, promotes CD8(+) T cells to maintain pro-inflammatory effector functions. The results from each of the previously mentioned studies demonstrate the importance of measuring cellular responses from TME-infiltrating immune cells as opposed to cells that remain in the periphery. To study the function of immune cells which infiltrate tumors using the Miltenyi Biotech isolation system, we have modified and optimized this antibody-based isolation procedure to obtain highly enriched populations of antigen presenting cells and tumor antigen-specific cytotoxic T lymphocytes. The protocol includes a detailed dissection of murine prostate tissue from a spontaneous prostate tumor model (TRansgenic Adenocarcinoma of the Mouse Prostate -TRAMP) and a subcutaneous melanoma (B16) tumor model followed by subsequent purification of various leukocyte populations.

7 Retraction Green tea catechins reduce invasive potential of human melanoma cells by targeting COX-2, PGE2 receptors and epithelial-to-mesenchymal transition. 2011

Singh, Tripti / Katiyar, Santosh K. ·Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America. ·PLoS One · Pubmed #22022384.

ABSTRACT: Melanoma is the most serious type of skin disease and a leading cause of death from skin disease due to its highly metastatic ability. To develop more effective chemopreventive agents for the prevention of melanoma, we have determined the effect of green tea catechins on the invasive potential of human melanoma cells and the molecular mechanisms underlying these effects using A375 (BRAF-mutated) and Hs294t (Non-BRAF-mutated) melanoma cell lines as an in vitro model. Employing cell invasion assays, we found that the inhibitory effects of green tea catechins on the cell migration were in the order of (-)-epigallocatechin-3-gallate (EGCG)>(-)-epigallocatechin>(-)-epicatechin-3-gallate>(-)-gallocatechin>(-)-epicatechin. Treatment of A375 and Hs294t cells with EGCG resulted in a dose-dependent inhibition of cell migration or invasion of these cells, which was associated with a reduction in the levels of cyclooxygenase (COX)-2, prostaglandin (PG) E(2) and PGE(2) receptors (EP2 and EP4). Treatment of cells with celecoxib, a COX-2 inhibitor, also inhibited melanoma cell migration. EGCG inhibits 12-O-tetradecanoylphorbol-13-acetate-, an inducer of COX-2, and PGE(2)-induced cell migration of cells. EGCG decreased EP2 agonist (butaprost)- and EP4 agonist (Cay10580)-induced cell migration ability. Moreover, EGCG inhibited the activation of NF-κB/p65, an upstream regulator of COX-2, in A375 melanoma cells, and treatment of cells with caffeic acid phenethyl ester, an inhibitor of NF-κB, also inhibited cell migration. Inhibition of melanoma cell migration by EGCG was associated with transition of mesenchymal stage to epithelial stage, which resulted in an increase in the levels of epithelial biomarkers (E-cadherin, cytokeratin and desmoglein 2) and a reduction in the levels of mesenchymal biomarkers (vimentin, fibronectin and N-cadherin) in A375 melanoma cells. Together, these results indicate that EGCG, a major green tea catechin, has the ability to inhibit melanoma cell invasion/migration, an essential step of metastasis, by targeting the endogenous expression of COX-2, PGE(2) receptors and epithelial-to-mesenchymal transition.

8 Retraction Silymarin targets β-catenin signaling in blocking migration/invasion of human melanoma cells. 2011

Vaid, Mudit / Prasad, Ram / Sun, Qian / Katiyar, Santosh K. ·Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America. ·PLoS One · Pubmed #21829575.

ABSTRACT: Metastatic melanoma is a leading cause of death from skin diseases, and is often associated with activation of Wnt/β-catenin signaling pathway. We have examined the inhibitory effect of silymarin, a plant flavanoid from Silybum marianum, on cell migration of metastasis-specific human melanoma cell lines (A375 and Hs294t) and assessed whether Wnt/β-catenin signaling is the target of silymarin. Using an in vitro invasion assay, we found that treatment of human melanoma cell lines with silymarin resulted in concentration-dependent inhibition of cell migration, which was associated with accumulation of cytosolic β-catenin, while reducing the nuclear accumulation of β-catenin (i.e., β-catenin inactivation) and reducing the levels of matrix metalloproteinase (MMP) -2 and MMP-9 which are the down-stream targets of β-catenin. Silymarin enhanced: (i) the levels of casein kinase 1α, glycogen synthase kinase-3β and phosphorylated-β-catenin on critical residues Ser(45), Ser(33/37) and Thr(41), and (ii) the binding of β-transducin repeat-containing proteins (β-TrCP) with phospho forms of β-catenin in melanoma cells. These events play important roles in degradation or inactivation of β-catenin. To verify whether β-catenin is a potent molecular target of silymarin, the effect of silymarin was determined on β-catenin-activated (Mel 1241) and β-catenin-inactivated (Mel 1011) melanoma cells. Treatment of Mel 1241 cells with silymarin or FH535, an inhibitor of Wnt/β-catenin pathway, significantly inhibited cell migration of Mel 1241 cells, which was associated with the elevated levels of casein kinase 1α and glycogen synthase kinase-3β, and decreased accumulation of nuclear β-catenin and inhibition of MMP-2 and MMP-9 levels. However, this effect of silymarin and FH535 was not found in Mel 1011 melanoma cells. These results indicate for the first time that silymarin inhibits melanoma cell migration by targeting β-catenin signaling pathway.

9 Retraction Foxp3-positive macrophages display immunosuppressive properties and promote tumor growth. 2011

Manrique, Soraya Zorro / Correa, Maria Adelaida Duque / Hoelzinger, Dominique B / Dominguez, Ana Lucia / Mirza, Noweeda / Lin, Hsi-Hsien / Stein-Streilein, Joan / Gordon, Siamon / Lustgarten, Joseph. ·Department of Immunology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA. ·J Exp Med · Pubmed #21670203.

ABSTRACT: Regulatory T cells (T reg cells) are characterized by the expression of the forkhead lineage-specific transcription factor Foxp3, and their main function is to suppress T cells. While evaluating T reg cells, we identified a population of Foxp3-positive cells that were CD11b(+)F4/80(+)CD68(+), indicating macrophage origin. These cells were observed in spleen, lymph nodes, bone marrow, thymus, liver, and other tissues of naive animals. To characterize this subpopulation of macrophages, we devised a strategy to purify CD11b(+)F4/80(+)Foxp3(+) macrophages using Foxp3-GFP mice. Analysis of CD11b(+)F4/80(+)Foxp3(+) macrophage function indicated that these cells inhibited the proliferation of T cells, whereas Foxp3(-) macrophages did not. Suppression of T cell proliferation was mediated through soluble factors. Foxp3(-) macrophages acquired Foxp3 expression after activation, which conferred inhibitory properties that were indistinguishable from natural Foxp3(+) macrophages. The cytokine and transcriptional profiles of Foxp3(+) macrophages were distinct from those of Foxp3(-) macrophages, indicating that these cells have different biological functions. Functional in vivo analyses indicated that CD11b(+)F4/80(+)Foxp3(+) macrophages are important in tumor promotion and the induction of T reg cell conversion. For the first time, these studies demonstrate the existence of a distinct subpopulation of naturally occurring macrophage regulatory cells in which expression of Foxp3 correlates with suppressive function.

10 Retraction Molecular mechanism of MART-1+/A*0201+ human melanoma resistance to specific CTL-killing despite functional tumor-CTL interaction. 2011

Jazirehi, Ali R / Baritaki, Stavroula / Koya, Richard C / Bonavida, Benjamin / Economou, James S. ·Department of Surgery, Molecular and Medical Pharmacology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, California, USA. ajazirehi@mednet.ucla.edu ·Cancer Res · Pubmed #21159666.

ABSTRACT: Durable responses in metastatic melanoma patients remain generally difficult to achieve. Adoptive cell therapy (ACT) with ex vivo engineered lymphocytes expressing high affinity T-cell receptors (TCRα/β) for the melanoma antigen MART-1₂₇₋₃₅/HLA-A*0201 [recognized by F5 cytotoxic T lymphocytes (F5 CTL)] has been found to benefit certain patients. However, many other patients are inherently unresponsive and/or relapse for unknown reasons. To analyze the basis for the acquired resistance and strategies to reverse it, we established F5 CTL-resistant (R) human melanoma clones from relatively sensitive parental lines under selective F5 CTL pressure. Surface MART-1₂₇₋₃₅/HLA-A*0201 in these clones was unaltered and F5 CTLs recognized and interacted with them similar to the parental lines. Nevertheless, the R clones were resistant to F5 CTL killing, exhibited hyperactivation of the NF-κB survival pathway, and overexpression of the antiapoptotic genes B cell lymphoma protein 2 (Bcl-2), Bcl-2 related gene (long alternatively spliced variant of Bcl-x gene; Bcl-(xL)), and myeloid cell differentiation 1 (Mcl-1). Sensitivity to F5 CTL-killing could be increased by pharmacological inhibition of the NF-κB pathway, Bcl-2 family members, or the proteasome, the latter of which reduced NF-κB activity and diminished antiapoptotic gene expression. Specific gene-silencing (by siRNA) confirmed the protective role of antiapoptotic factors by reversing R clone resistance. Together, our findings suggest that long-term immunotherapy may impose a selection for the development of resistant cells that are unresponsive to highly avid and specific melanoma-reactive CTLs, despite maintaining expression of functional peptide:MHC complexes, due to activation of antiapoptotic signaling pathways. Though unresponsive to CTL, our results argue that resistant cells can be resensitized to immunotherapy with coadministration of targeted inhibitors to antiapoptotic survival pathways.

11 Retraction Non-thermal plasma induces apoptosis in melanoma cells via production of intracellular reactive oxygen species. 2011

Sensenig, Rachel / Kalghatgi, Sameer / Cerchar, Ekaterina / Fridman, Gregory / Shereshevsky, Alexey / Torabi, Behzad / Arjunan, Krishna Priya / Podolsky, Erica / Fridman, Alexander / Friedman, Gary / Azizkhan-Clifford, Jane / Brooks, Ari D. ·Department of Surgery, College of Medicine, Drexel University, Philadelphia, PA 19102, USA. ·Ann Biomed Eng · Pubmed #21046465.

ABSTRACT: Non-thermal atmospheric pressure dielectric barrier discharge (DBD) plasma may provide a novel approach to treat malignancies via induction of apoptosis. The purpose of this study was to evaluate the potential of DBD plasma to induce apoptosis in melanoma cells. Melanoma cells were exposed to plasma at doses that did not induce necrosis, and cell viability and apoptotic activity were evaluated by Trypan blue exclusion test, Annexin-V/PI staining, caspase-3 cleavage, and TUNEL® analysis. Trypan blue staining revealed that non-thermal plasma treatment significantly decreased the viability of cells in a dose-dependent manner 3 and 24 h after plasma treatment. Annexin-V/PI staining revealed a significant increase in apoptosis in plasma-treated cells at 24, 48, and 72 h post-treatment (p < 0.001). Caspase-3 cleavage was observed 48 h post-plasma treatment at a dose of 15 J/cm(2). TUNEL® analysis of plasma-treated cells demonstrated an increase in apoptosis at 48 and 72 h post-treatment (p < 0.001) at a dose of 15 J/cm(2). Pre-treatment with N-acetyl-L: -cysteine (NAC), an intracellular reactive oxygen species (ROS) scavenger, significantly decreased apoptosis in plasma-treated cells at 5 and 15 J/cm(2). Plasma treatment induces apoptosis in melanoma cells through a pathway that appears to be dependent on production of intracellular ROS. DBD plasma production of intracellular ROS leads to dose-dependent DNA damage in melanoma cells, detected by γ-H2AX, which was completely abrogated by pre-treating cells with ROS scavenger, NAC. Plasma-induced DNA damage in turn may lead to the observed plasma-induced apoptosis. Since plasma is non-thermal, it may be used to selectively treat malignancies.

12 Retraction Berberine, an isoquinoline alkaloid, inhibits melanoma cancer cell migration by reducing the expressions of cyclooxygenase-2, prostaglandin E₂ and prostaglandin E₂ receptors. 2011

Singh, Tripti / Vaid, Mudit / Katiyar, Nandan / Sharma, Samriti / Katiyar, Santosh K. ·Department of Dermatology, University of Alabama at Birmingham, 35294, USA. ·Carcinogenesis · Pubmed #20974686.

ABSTRACT: Melanoma is the leading cause of death from skin disease due, in large part, to its propensity to metastasize. We have examined the effect of berberine, an isoquinoline alkaloid, on human melanoma cancer cell migration and the molecular mechanisms underlying these effects using melanoma cell lines, A375 and Hs294. Using an in vitro cell migration assay, we show that over expression of cyclooxygenase (COX)-2, its metabolite prostaglandin E₂ (PGE₂) and PGE₂ receptors promote the migration of cells. We found that treatment of A375 and Hs294 cells with berberine resulted in concentration-dependent inhibition of migration of these cells, which was associated with a reduction in the levels of COX-2, PGE₂ and PGE₂ receptors (EP2 and EP4). Treatment of cells with celecoxib, a COX-2 inhibitor, or transient transfection of cells with COX-2 small interfering RNA, also inhibited cell migration. Treatment of the cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), an inducer of COX-2 or PGE₂, enhanced cell migration, whereas berberine inhibited TPA- or PGE₂-promoted cell migration. Berberine reduced the basal levels as well as PGE₂-stimulated expression levels of EP2 and EP4. Treatment of the cells with the EP4 agonist stimulated cell migration and berberine blocked EP4 agonist-induced cell migration activity. Moreover, berberine inhibited the activation of nuclear factor-kappa B (NF-κB), an upstream regulator of COX-2, in A375 cells, and treatment of cells with caffeic acid phenethyl ester, an inhibitor of NF-κB, inhibited cell migration. Together, these results indicate for the first time that berberine inhibits melanoma cell migration, an essential step in invasion and metastasis, by inhibition of COX-2, PGE₂ and PGE₂ receptors.

13 Retraction RETRACTED: A novel class of specific Hsp90 small molecule inhibitors demonstrate in vitro and in vivo anti-tumor activity in human melanoma cells. 2011

Mehta, Pramod P / Kung, Pei-Pei / Yamazaki, Shinji / Walls, Marlena / Shen, Andrea / Nguyen, Leslie / Gehring, Michael R / Los, Gerrit / Smeal, Tod / Yin, Min-Jean. ·Pfizer Worldwide Research and Development, Oncology Research, 10724 Science Center Drive, San Diego, CA 92121, United States. ·Cancer Lett · Pubmed #20926183.

ABSTRACT: This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Authors. Following an investigation by Pfizer, Figures 2, 5B and 5C appear to be duplications and hence the conclusions in the manuscript cannot be verified. The Authors apologize for this inconvenience.

14 Retraction MicroRNA-340-mediated degradation of microphthalmia-associated transcription factor mRNA is inhibited by the coding region determinant-binding protein. 2010

Goswami, Srikanta / Tarapore, Rohinton S / Teslaa, Jessica J / Grinblat, Yevgenya / Setaluri, Vijayasaradhi / Spiegelman, Vladimir S. ·Department of Dermatology and the Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA. ·J Biol Chem · Pubmed #20439467.

ABSTRACT: Alternative cleavage and polyadenylation generate multiple transcript variants of mRNA isoforms with different length of 3'-untranslated region (UTR). Alternative cleavage and polyadenylation enable differential post-transcriptional regulation of transcripts via the availability of different cis-acting elements in 3'-UTRs. Microphthalmia-associated transcription factor (MITF) is a master regulator of melanocyte development and melanogenesis. It has also been implicated in melanoma development. Here we show that melanoma cells favor the expression of MITF mRNA with shorter 3'-UTR. This isoform of mRNA is regulated by microRNA, miR-340. miR-340 interacts with two of its target sites on the 3'-UTR of MITF mRNA, causing mRNA degradation and decreased expression and activity of MITF. On the other hand, the RNA-binding protein coding region determinant-binding protein, shown to be highly expressed in melanoma, directly binds to the 3'-UTR of MITF mRNA and prevents the binding of miR-340 to its target sites, resulting in stabilization of the MITF transcript and elevated expression and transcriptional activity of MITF. This interplay between RNA-binding protein and miRNA describes the important mechanism of regulation of MITF in melanocytes and malignant melanomas.

15 Retraction Synthetic N-acetyl-D-glucosamine based fully branched tetrasaccharide, a mimetic of the endogenous ligand for CD69, activates CD69+ killer lymphocytes upon dimerization via a hydrophilic flexible linker. 2010

Kovalová, Anna / Ledvina, Miroslav / Saman, David / Zyka, Daniel / Kubícková, Monika / Zídek, Lukás / Sklenár, Vladimír / Pompach, Petr / Kavan, Daniel / Bílý, Jan / Vanek, Ondrej / Kubínková, Zuzana / Libigerová, Martina / Ivanová, Ljubina / Antolíková, Mária / Mrázek, Hynek / Rozbeský, Daniel / Hofbauerová, Katerina / Kren, Vladimír / Bezouska, Karel. ·Institute of Organic Chemistry and Biochemistry, VVI, Academy of Sciences of the Czech Republic, Prague, Czech Republic. ·J Med Chem · Pubmed #20433142.

ABSTRACT: On the basis of the highly branched ovomucoid-type undecasaccharide that had been shown previously to be an endogenous ligand for CD69 leukocyte receptor, a systematic investigation of smaller oligosaccharide mimetics was performed based on linear and branched N-acetyl-d-hexosamine homooligomers prepared synthetically using hitherto unexplored reaction schemes. The systematic structure-activity studies revealed the tetrasaccharide GlcNAcbeta1-3(GlcNAcbeta1-4)(GlcNAcbeta1-6)GlcNAc (compound 52) and its alpha-benzyl derivative 49 as the best ligand for CD69 with IC(50) as high as 10(-9) M. This compound thus approaches the affinity of the classical high-affinity neoglycoprotein ligand GlcNAc(23)BSA. Compound 68, GlcNAc tetrasaccharide 52 dimerized through a hydrophilic flexible linker, turned out to be effective in activating CD69(+) lymphocytes. It also proved efficient in enhancing natural killing in vitro, decreasing the growth of tumors in vivo, and activating the CD69(+) tumor infiltrating lymphocytes examined ex vivo. This compound is thus a candidate for carbohydrate-based immunomodulators with promising antitumor potential.

16 Retraction CTL activation using the natural low-affinity epitope 222-229 from tyrosinase-related protein 1 leads to tumor rejection. 2009

Pavelko, Kevin D / Hansen, Michael J / Pease, Larry R. ·Department of Immunology, College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA. ·Cancer Res · Pubmed #19276379.

ABSTRACT: Vaccine strategies for cancer immunotherapy have focused on peptide ligands with high affinity for MHC class I. Largely, these vaccines have not been therapeutic. We have examined the peptide specificity of a strongly protective T-cell response that eradicates established B16 melanoma and find that the recognized epitope is generated by a low-affinity MHC class I ligand from tyrosinase-related protein 1 (TRP1). Cytotoxic T-cell responses are induced against TRP1(222-229) by several vaccination schemes using a Toll-like receptor agonist, T regulatory cell depletion, or the immune modulator B7-DCXAb to drive immunity. TRP1(222) CTL are generated from multiple antigen sources, including antigens expressed by tumors growing in situ, tumor cell lysates, and peptide vaccines. The key finding in this study is that protection from freshly implanted or established B16 tumors is primarily mediated by TRP1(222)-specific CTL and not by CTL specific for more traditional melanoma antigens such as TRP2 or gp100. This finding challenges the assumption that the optimal peptide antigens for cancer vaccines are high-affinity MHC ligands. We propose that when administered appropriately, native low-affinity MHC ligands are optimal inducers of immunotherapeutic CTL.