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- Darabi, Anna, et al.
(author)
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HLA-I Antigen Presentation and Tapasin Influence Immune Responses Against Malignant Brain Tumors - Considerations for Successful Immunotherapy.
- 2014
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In: Anti-Cancer Agents in Medicinal Chemistry. - 1875-5992. ; 14:8, s. 1094-1100
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Journal article (peer-reviewed)abstract
- Human leukocyte antigen class I (HLA-I) presents antigenic peptides to cytotoxic CD8+ T cells (CTLs). This is a pivotal step in the generation of CTL responses. Both the quantity and quality of peptide-HLA-I (pHLA-I) complexes are crucial for CTL responses, but the level of HLA-I expression per se is also directly involved in dictating NK-cell responses. Antigen processing machinery (APM) proteins are involved in the maturation of HLA-I and in the selection of which peptides are - or are not - presented. Thus, these proteins are key players in shaping the immune response to cells in health and disease. In this review, we recap the most important features of APM components and their synergistic work to assure proper pHLA-I cell surface expression. We pay special attention to the HLA-I dedicated multifunctional protein, tapasin, and in relation to the different tapasin-dependency of HLA-I allomorphs we also discuss allomorph specific traits in maturation, structure and linkage to malignant diseases and brain tumors in particular. We next discuss the possibilities of restoring or manipulating the immune responses against brain tumors. In this context we discuss IFNγ therapy, cytostatics and irradiation. Finally, we integrate current views and knowledge to set the direction for future emphasis in the area of immunotherapy against brain tumors.
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- Gouleni, Niki, et al.
(author)
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Anticancer Potential of Novel Cinnamoyl Derivatives against U87MG and SHSY-5Y Cell Lines
- 2024
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In: Anti-Cancer Agents in Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 1871-5206 .- 1875-5992. ; 24:1, s. 39-49
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Journal article (peer-reviewed)abstract
- Background: Glioblastoma multiforme (GBM) is probably the most malignant and aggressive brain tumor belonging to the class of astrocytomas. The considerable aggressiveness and high malignancy of GBM make it a tumor that is difficult to treat. Here, we report the synthesis and biological evaluation of eighteen novel cinnamoyl derivatives (3a-i and 4a-i) to obtain more effective antitumor agents against GBM. Methods: The chemical structures of novel cinnamoyl derivatives (3a-i and 4a-i) were confirmed by NMR and MS analyses. The physicochemical properties and evaluation of the ADME profile of 3a-i and 4a-i were performed by the preADMETlab2.0 web program. Cinnamoyl derivatives 3a-i and 4a-i were tested in vitro for their cytotoxicity against the human healthy fibroblast (HDFa) cells using an MTT cell viability assay. Derivatives with no toxicity on HDFa cells were tested both on human glioblastoma (U87MG) and neuroblastoma (SHSY5Y) cells, chosen as an experimental model of brain tumors. Cell death mechanisms were analyzed by performing flow cytometry analyses. Results: Cinnamoyl derivatives 3a-i and 4a-i showed good physicochemical and ADME properties suggesting that these compounds could be developed as oral drugs endowed with a high capability to cross the blood-brain barrier. Compounds (E)-1-methoxy-4-(2-(phenylsulfonyl)vinyl)benzene (2c) and (E)-N-benzyl-N-(2-(cyclohexylamino)-2-oxoethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide (3e) did not show cytotoxicity on healthy human fibroblast cells up to 100 µg/mL. The most anticarcinogenic molecule, compound 3e, emerged as the most potent anticancer candidate in this study. Flow cytometry results showed that compound 3e (25 µg/mL) application resulted in nearly 86% and 84% cytotoxicity in the U87MG and the SHSY-5Y cell lines, respectively. Compound 2c (25 µg/mL) resulted in 81% and 82% cytotoxicity in the U87MG and the SHSY-5Y cell lines, respectively. Conclusion: Cinnamoyl derivative 3e inhibits the proliferation of cultured U87MG and SHSY-5Y cells by inducing apoptosis. Further detailed research will be conducted to confirm these data in in vivo experimental animal models.
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- Hellmén, Eva
(author)
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Evaluation of Angiogenesis Process after Metformin and LY294002 Treatment in Mammary Tumor
- 2019
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In: Anti-Cancer Agents in Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 1871-5206 .- 1875-5992. ; 19, s. 655-666
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Journal article (peer-reviewed)abstract
- Background: The angiogenesis process is regulated by many factors, such as Hypoxia-Inducible Factor-1 (HIF-1) and Vascular Endothelial Growth Factor (VEGF). Metformin has demonstrated its ability to inhibit cell growth and the LY294002 is the major inhibitor of PI3K/AKT/mTOR pathway that has antiangiogenic properties.Methods: Canine mammary tumor cell lines CMT-U229 and CF41 were treated with metformin and LY294002. Cell viability, protein and gene expression of VEGF and HIF-1 were determined in vitro. For the in vivo study, CF41 cells were inoculated in female athymic nude mice treated with either metformin or LY294002. The microvessel density by immunohistochemistry for CD31 as well as the gene and protein expression of HIF-1 and VEGF were evaluated.Results: The treatment with metformin and LY294002 was able to reduce the cellular viability after 24 hours. The protein and gene expression of HIF-1 and VEGF decreased after treatment with metformin and LY294002. In the in vivo study, there was a decrease in tumor size, protein and gene expression of HIF-1 and VEGFA, in addition to the decreasing of CD31 expression after all treatments.Conclusion: Our results demonstrate the effectiveness of metformin and LY294002 in controlling the angiogenesis process in mammary tumors by VEGF and HIF-1, the most important angiogenic markers.
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- Johansson, Martin, et al.
(author)
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Cancer therapy : targeting cell cycle regulators
- 2008
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In: Anti-cancer agents in medicinal chemistry. - : Bentham Science Publishers. - 1871-5206 .- 1875-5992. ; 8:7, s. 723-31
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Research review (peer-reviewed)abstract
- Cyclins and CDKs play critical roles in DNA synthesis and cell division. Alterations in their function may lead to the disruption of normal cell growth and apoptosis, and subsequently, result in carcinogenesis. Elevated levels of cyclins and CDKs are frequently observed in a wide range of different types of human cancers. Understanding of molecular mechanisms underlying the cell cycle effects in response to the chemotherapeutic agents is of great importance for improving the efficacy of targeted therapeutics and overcoming resistance to chemotherapeutic agents. Despite the clinical applications of cell cycle specific chemotherapeutic agents, there is still an urgent need to develop novel drugs that can target multiple sites and pathways of the cell cycle while avoiding drug induced cytotoxicity. In this review article, we will summarize the development of novel agents that specifically target cell cycle pathways in human cancer. We will discuss drugs that can directly interfere with the mitotic process of tumor cells. Moreover, we tend to address the significance of using small molecule CDK inhibitors that are derived from natural products.
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- Ma, C, et al.
(author)
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Translational gap in glioma research
- 2014
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In: Anti-cancer agents in medicinal chemistry. - : Bentham Science Publishers Ltd.. - 1875-5992 .- 1871-5206. ; 14:8, s. 1110-1120
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Journal article (peer-reviewed)
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| 10. |
- Nilsson, Ola, 1957, et al.
(author)
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New medical strategies for midgut carcinoids.
- 2010
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In: Anti-cancer agents in medicinal chemistry. - 1875-5992. ; 10:3, s. 250-269
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Research review (peer-reviewed)abstract
- Patients with well-differentiated neuroendocrine tumours of the gastrointestinal tract often present with metastases and hormonal symptoms. These patients can be palliated by interventional tumour reduction and medical treatment with somatostatin analogues; no effective chemotherapy is available. Radionuclide therapy via somatostatin receptors is one new therapeutic alternative. The recognition that neuroendocrine tumours express specific receptors for growth factors and chemokines, which are of importance for tumour growth, vascularization, and spread, may open the way for new therapeutic approaches. The signalling pathways in carcinoid tumours are incompletely explored. This review summarizes potential new treatment strategies from clinical and experimental studies, e.g. inhibition of angiogenesis, targeting of growth factors or their receptors by tyrosine kinase inhibitors, interference with specific cellular pathways (mTOR, PI3K, RAS/RAF, Notch), and also inhibition of the proteasome and histone deacetylation. Combining targeted therapy with chemotherapy, or using drugs to sensitize for radionuclide therapy, may enhance the treatment outcome.
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