Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs (CpG-ODN) act as potent immune stimulators by activating innate immunity through toll-like receptor 9. These immunomodulatory effects of CpG-ODN have been reported to be associated with anti-tumor immunity. In this study, we used a murine B16F10 melanoma model and a CT26 colon cancer model to assess whether CpG-ODN-based immunotherapy was effective in inhibiting tumor cells that have already metastasized to distant organs. Systemic administration of CpG-ODN after melanoma cell injection resulted in a significant inhibition of pulmonary colonization. When CpG-ODN was administered after tumor cell injection, it also inhibited pulmonary metastasis of the tumor cells, albeit to a lesser degree in the latter case. Systemic administration of CpG-ODN after subcutaneous inoculation of CT26 colon cancer cells diminished pulmonary metastasis from the primary tumor sites. Additionally, CpG-ODN also inhibited the growth of pulmonary colonization of the colon tumor cells when CpG-ODN was administered after the primary tumors had been surgically removed. These data indicate that CpG-ODN was effective in inhibiting pulmonary metastasis of the B16F10 melanoma and CT26 colon cancer cells, as well as the growth of metastasized tumor cells. Our results suggest that CpG-ODN-based immunotherapy may be beneficial in controlling micrometastasis after surgery in clinical settings.
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PMID:CpG-ODN-based immunotherapy is effective in controlling the growth of metastasized tumor cells. 1895 69

Nine halogenated monoterpenes isolated from the red alga Plocamium cartilagineum have been evaluated for their cytotoxic effects on the tumor cell lines CT26 (murine colon adenocarcinoma), SW480 (human colon adenocarcinoma), HeLa (human cervical adenocarcinoma) and SkMel28 (human malignant melanoma) with several multidrug resistance mechanisms and the mammalian non-tumor cell line CHO (Chinese hamster ovary cells). The activities of these compounds were compared with those of the insecticide gamma-hexachlorocyclohexane (lindane) due to chemical structure similarities. Compounds 1, 2, 3, and 5 exhibited selective cytotoxicity against colon and cervical adenocarcinoma cells. Interestingly, the effect of compound 3 was specific and irreversible to human colon adenocarcinoma SW480 cells, which overexpress the transmembrane P-glycoprotein often related to chemoresistance. None of the anti-tumor doses of these compounds was cytotoxic against CHO cells. Furthermore, analysis of cellular extracts after incubation with the test compounds and rotenone (positive uptake control) demonstrated the intracellular accumulation of 1, 2, 3, and 5.
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PMID:Cytotoxic activity of halogenated monoterpenes from Plocamium cartilagineum. 1899 98

Cancer progression is facilitated by blood coagulation. Anticoagulants, such as Hirudin and low molecular weight heparins (LMWHs), reduce metastasis mainly by inhibition of thrombin formation and L- and P-selectin-mediated cell-cell adhesion. It is unknown whether the effects are dependent on cancer cell type. The effects of anticoagulants on tumor development of K1735 and B16 melanoma cells and CT26 colon cancer cells were investigated in mouse lung. Tumor load was determined noninvasively each week up to day 21 in all experiments using bioluminescence imaging. Effects of anticoagulants on tumor development of the three cell lines were correlated with the fibrin/fibrinogen content in the tumors, expression of tissue factor (TF), protease activated receptor (PAR)-1 and -4 and CD24, a ligand of L- and P-selectins. Hirudin inhibited tumor development of B16 cells in lungs completely but did not affect tumor growth of K1735 and CT26 cells. Low molecular weight heparin did not have an effect on K1735 melanoma tumor growth either. TF and PAR-4 expression was similar in the three cell lines. PAR-1 and CD24 were hardly expressed by K1735, whereas CT26 cells expressed low levels and B16 high levels of PAR-1 and CD24. Fibrin content of the tumors was not affected by LMWH. It is concluded that effects of anticoagulants are dependent on cancer cell type and are correlated with their CD24 and PAR-1 expression.
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PMID:Differential effects of anticoagulants on tumor development of mouse cancer cell lines B16, K1735 and CT26 in lung. 1906 86

Cancer results from the concerted performance of malignant cells and stromal cells. Cell types populating the microenvironment are enlisted by the tumor to secrete a host of growth-promoting cues, thus upholding tumor initiation and progression. Platelet-derived growth factors (PDGF) support the formation of a prominent tumor stromal compartment by as of yet unidentified molecular effectors. Whereas PDGF-CC induces fibroblast reactivity and fibrosis in a range of tissues, little is known about the function of PDGF-CC in shaping the tumor-stroma interplay. Herein, we present evidence for a paracrine signaling network involving PDGF-CC and PDGF receptor-alpha in malignant melanoma. Expression of PDGFC in a mouse model accelerated tumor growth through recruitment and activation of different subsets of cancer-associated fibroblasts. In seeking the molecular identity of the supporting factors provided by cancer-associated fibroblasts, we made use of antibody arrays and an in vivo coinjection model to identify osteopontin as the effector of the augmented tumor growth induced by PDGF-CC. In conclusion, we establish paracrine signaling by PDGF-CC as a potential drug target to reduce stromal support in malignant melanoma.
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PMID:Paracrine signaling by platelet-derived growth factor-CC promotes tumor growth by recruitment of cancer-associated fibroblasts. 1911 22

Paraneoplastic retinopathies (PR), including cancer-associated retinopathy (CAR) or the closely related melanoma-associated retinopathy (MAR) occur in a small subset of patients with retinal degeneration and systemic cancer. This autoimmune syndrome is characterized by sudden, progressive loss of vision in association with circulating anti-retinal autoantibodies. The PR syndromes are heterogeneous, may produce a number of ocular symptoms, and may be associated with several different neoplasms, including lung, breast, prostate, gynecological, and colon cancer, melanoma, and hematologic malignancies. We examined the onset of retinopathy in correlation to the diagnosis of cancer and the presence of specific anti-retinal autoantibodies in PR patients. In some patients without diagnosed malignant tumors, the onset of ocular symptoms and the presence of autoantibodies preceded the diagnosis of cancer by months to years, including anti-recoverin, anti-transducin-alpha, and anti-carbonic anhydrase II antibodies. Although anti-retinal autoantibodies may not be a good predictor of a specific neoplasm, they can be used as biomarkers for different subtypes of retinopathy. Identification of autoantibodies involved in autoimmune-mediated PR will help elucidate the mechanisms underlying the PR syndromes and develop targeted therapies for these sight-threatening disorders.
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PMID:Autoantibody targets and their cancer relationship in the pathogenicity of paraneoplastic retinopathy. 1916 57

This study evaluated the effects of cohabitation with a B16F10 melanoma-bearer cage mate on behavior and immune functions in mice. Five different experiments were conducted. In each of them, the female mice were divided into two groups: control and experimental. One mouse of each control pair was kept undisturbed and called "companion of health partner" (CHP). One mouse of each experimental pair was inoculated with B16F10 cells and the other, the subject of this study, was called "companion sick partner" (CSP). On Day 20 of cohabitation, behavior and immune parameters from CHP and CSP mice were analyzed. In comparison to the CHP, the CSP mice: (1) presented an increased general locomotion in the open field and a decreased exploration time and number of entries in the plus-maze open arms; (2) had an enhanced expression of the CD80 costimulatory molecule on Iab(+)CD11c(+) spleen cells, but no differences were found on lymph nodes cells; (3) presented an altered differentiation of bone marrow cells in the presence of GM-CSF, IL-4, and LPS in vitro, resulting in a lower percentage of Iab(+)CD80(+) cells; (4) had a deficit in the establishment of a Delayed Type of Hypersensitivity to ovalbumin, which was associated to an in vitro proliferation of an IL-10-producing lymphocyte subpopulation after ovalbumin stimulation. Corticosterone levels detected on Day 20 of cohabitation were similar in CHP and CSP mice. It is shown here that DCs phenotype in mice is affected by conditions associated with behavioral alterations indicative of an anxiety-like state induced by the cohabitation with a tumor-bearer conspecific. This phenomenon occurred probably through a nondependent corticosterone mechanism.
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PMID:Cohabitation with a B16F10 melanoma-bearer cage mate influences behavior and dendritic cell phenotype in mice. 1923 59

Neuroimmunomodulation describes the field focused on understanding the mechanisms by which the central nervous system interacts with the immune system, potentially leading to changes in animal behavior. Nonetheless, not many articles dealing with neuroimmunomodulation employ behavior as an analytical endpoint. Even fewer papers deal with social status as a possible modifier of neuroimmune phenomena. In the described sets of experiments, we tackle both, using a paradigm of social dominance and subordination. We first review data on the effects of different ranks within a stable hierarchical relationship. Submissive mice in this condition display more anxiety-like behaviors, have decreased innate immunity, and show a decreased resistance to implantation and development of melanoma metastases in their lungs. This suggests that even in a stable, social, hierarchical rank, submissive animals may be subjected to higher levels of stress, with putative biological relevance to host susceptibility to disease. Second, we review data on how dominant and submissive mice respond differentially to lipopolysaccharide (LPS), employing a motivational perspective to sickness behavior. Dominant animals display decreased number and frequency in several aspects of behavior, particularly agonistic social interaction, that is, directed toward the submissive cage mate. This was not observed in submissive mice that maintained the required behavior expected by its dominant mate. Expression of sickness behavior relies on motivational reorganization of priorities, which are different along different social ranks, leading to diverse outcomes. We suggest that in vitro assessment of neuroimmune phenomena can only be understood based on the behavioral context in which they occur.
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PMID:Behavior: a relevant tool for brain-immune system interaction studies. 1923 34

The ability to instantly create a state of immunity as achieved in the passive transfer of hyperimmune globulin has had a tremendous impact on public health. Unlike passive immunization, active immunization, which is the foundation of vaccinology, is an anticipatory strategy with inherent limitations. Here we show that elements of active and passive immunization can be combined to create an effective chemistry-driven approach to vaccinology. Reactive immunization was used to create a reservoir of covalent polyclonal antibodies in 3 mouse strains that were subsequently engrafted with syngeneic CT26 colon or B16F10 melanoma tumors. Upon administration of designed integrin alpha(v)beta(3) and alpha(v)beta(5) adapter ligands, the induced covalent polyclonal antibodies self-assembled with the adapter ligands and the animals mounted an instant, chemically programmed, polyclonal response against the implanted tumors. Significant therapeutic responses were observed without recourse to adjuvant therapy. The chemically programmed immune responses were driven by antibody-dependent cellular cytotoxicity and complement-directed cytotoxicity. We suggest that this type of chemistry-driven approach to vaccinology is underexplored and may provide routes to vaccines to protect against diseases that have proven intractable to biology-driven vaccine approaches.
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PMID:Instant immunity through chemically programmable vaccination and covalent self-assembly. 1925 30

Biot2 is a novel murine testis-specific gene that was first identified using the SEREX technique, and named by our laboratory. Using conventional RT-PCR and real time RT-PCR, we tested the expression profile of Biot2 in normal tissues and various murine tumor cell lines. Using RNA interference, we studied the biological function of Biot2 in tumorigenesis. We applied various types of growth assay, such as the in vitro MTT, colony-forming and BrdU incorporation assays, along with in vivo tumorigenicity assays, to reveal its inhibition of tumor cell proliferation. The results revealed that the Biot2 transcript was detected only and strongly in the testis tissues and abundantly in five types of murine cancer cell line. Treating B16 murine melanoma, LL/2 murine Lewis lung carcinoma and CT26 murine colorectal adenocarcinoma with special shRNA targeting Biot2 can significantly reduce the proliferation rate of these three tumor cell lines in vitro, as measured by the MTT, colony-forming and BrdU incorporation assays. The tumorigenicity of the CT26 cells transfected with special shRNA targeting Biot2 was also decreased distinctly in vivo compared with the control. It was therefore concluded that Biot2 plays a key role in tumorigenesis and could be a potential target for biotherapy.
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PMID:RNA interference against Biot2, a novel mouse testis-specific gene, inhibits the growth of tumor cells. 1927 78

WNT5A is a cancer-associated gene involved in invasion and metastasis of melanoma, breast cancer, pancreatic cancer, and gastric cancer. WNT5A transduces signals through Frizzled, ROR1, ROR2 or RYK receptors to beta-catenin-TCF/LEF, DVL-RhoA-ROCK, DVL-RhoB-Rab4, DVL-Rac-JNK, DVL-aPKC, Calcineurin-NFAT, MAP3K7-NLK, MAP3K7-NF-kappaB, and DAG-PKC signaling cascades in a context-dependent manner. SNAI1 (Snail), CD44, G3BP2, and YAP1 are WNT5A target genes. We and other groups previously reported that IL6- or LIF-induced signaling through JAK-STAT3 signaling cascade is involved in WNT5A upregulation (STAT3-WNT5A signaling loop). Here, refined integrative genomic analyses of WNT5A were carried out to elucidate other mechanisms of WNT5A transcription. The WNT5A gene was found to encode two isoforms by using alternative first exons 1A and 1B. Quadruple Smad-binding elements (SBEs), single Sp1-binding site (GC-box), PPARgamma-binding site, C/EBP-binding site and bHLH-binding site within the promoter A region, 5'-adjacent to exon 1A, were conserved in human WNT5A, chimpanzee WNT5A, mouse Wnt5a, and rat Wnt5a. NF-kappaB-binding site, CUX1-binding site, double SBEs and double GC-boxes within the promoter B region, 5'-adjacent to exon 1B, were conserved in mammalian WNT5A orthologs. Quadruple FOX-binding sites and double SBEs within ultra-conserved intron 1 were also conserved in mammalian WNT5A orthologs. Conserved NF-kappaB-binding site within the WNT5A promoter B region elucidated the mechanisms that TNFalpha and toll-like receptor (TLR) signals upregulate WNT5A via MAP3K7. Quadruple FOX-binding sites rather than GLI-binding site revealed that Hedgehog signals induce WNT5A upregulation indirectly via FOX family members, such as FOXA2, FOXC2, FOXE1, FOXF1 and FOXL1. TGFbeta signals were found to upregulate WNT5A expression directly through the Smad complex, and also indirectly through Smad-induced CUX1 and MAP3K7-mediated NF-kappaB. Together these facts indicate that WNT5A is transcribed based on multiple mechanisms, such as NF-kappaB, Hedgehog, TGFbeta, and Notch signaling cascades.
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PMID:Transcriptional mechanisms of WNT5A based on NF-kappaB, Hedgehog, TGFbeta, and Notch signaling cascades. 1942 2


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