scholarly journals Curcumin as an Epigenetic Therapeutic Agent in Myelodysplastic Syndromes (MDS)

2021 ◽  
Vol 23 (1) ◽  
pp. 411
Author(s):  
Xiaoqing Xie ◽  
Daria Frank ◽  
Pradeep Kumar Patnana ◽  
Judith Schütte ◽  
Yahya Al-Matary ◽  
...  
Keyword(s):  
Therapeutic Agent ◽  
Molecular Level ◽  
Therapy Outcome ◽  
Open Chromatin ◽  
Epigenetic Changes ◽  
Curcumin Treatment ◽  
Free Survival ◽  
Cell Lineages ◽  
Haematopoietic Cells ◽  
Leukaemic Cells

Growth Factor Independence 1 (GFI1) is a transcription factor with an important role in the regulation of development of myeloid and lymphoid cell lineages and was implicated in the development of myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). Reduced expression of GFI1 or presence of the GFI1-36N (serine replaced with asparagine) variant leads to epigenetic changes in human and murine AML blasts and accelerated the development of leukaemia in a murine model of human MDS and AML. We and other groups previously showed that the GFI1-36N allele or reduced expression of GFI1 in human AML blasts is associated with an inferior prognosis. Using GFI1-36S, -36N -KD, NUP98-HOXD13-tg mice and curcumin (a natural histone acetyltransferase inhibitor (HATi)), we now demonstrate that expansion of GFI1-36N or –KD, NUP98-HODXD13 leukaemic cells can be delayed. Curcumin treatment significantly reduced AML progression in GFI1-36N or -KD mice and prolonged AML-free survival. Of note, curcumin treatment had no effect in GFI1-36S, NUP98-HODXD13 expressing mice. On a molecular level, curcumin treatment negatively affected open chromatin structure in the GFI1-36N or -KD haematopoietic cells but not GFI1-36S cells. Taken together, our study thus identified a therapeutic role for curcumin treatment in the treatment of AML patients (homo or heterozygous for GFI1-36N or reduced GFI1 expression) and possibly improved therapy outcome.

scholarly journals Nanomaterial-Mediated Theranostics for Vascular Diseases

2020 ◽  
Vol 2 (1) ◽  
pp. 1-15
Author(s):  
Swati Agrawal ◽  
Sunil K. Nooti ◽  
Harbinder Singh ◽  
Vikrant Rai
Keyword(s):  
Peripheral Arterial Disease ◽  
Therapeutic Agent ◽  
Molecular Level ◽  
Vascular Diseases ◽  
Arterial Disease ◽  
Imaging Studies ◽  
Leg Muscles ◽  
Diagnostic Agents ◽  
Peripheral Arterial ◽  
Complementary Strategy

Nanotechnology could offer a new complementary strategy for the treatment of vascular diseases including coronary, carotid, or peripheral arterial disease due to narrowing or blockage of the artery caused by atherosclerosis. These arterial diseases manifest correspondingly as angina and myocardial infarction, stroke, and intermittent claudication of leg muscles during exercise. The pathogenesis of atherosclerosis involves biological events at the cellular and molecular level, thus targeting these using nanomaterials precisely and effectively could result in a better outcome. Nanotechnology can mitigate the pathological events by enhancing the therapeutic efficacy of the therapeutic agent by delivering it at the point of a lesion in a controlled and efficacious manner. Further, combining therapeutics with imaging will enhance the theranostic ability in atherosclerosis. Additionally, nanoparticles can provide a range of delivery systems for genes, proteins, cells, and drugs, which individually or in combination can address various problems within the arteries. Imaging studies combined with nanoparticles helps in evaluating the disease progression as well as the response to the treatment because imaging and diagnostic agents can be delivered precisely to the targeted destinations via nanocarriers. This review focuses on the use of nanotechnology in theranostics of coronary artery and peripheral arterial disease.

The classification of leukaemia

2010 ◽  
pp. 4221-4228
Author(s):  
Wendy N. Erber
Keyword(s):  
Bone Marrow ◽  
Characteristic Feature ◽  
Lymph Nodes ◽  
Malignant Neoplasm ◽  
Normal Bone Marrow ◽  
Neoplastic Cells ◽  
Normal Bone ◽  
Haematopoietic Cells ◽  
Leukaemic Cells

Leukaemia is a malignant neoplasm of haematopoietic cells originating in the marrow and spreading to the blood and other tissues, such as the lymph nodes, spleen, and liver. The characteristic feature of the neoplastic cells is that they retain the ability to proliferate but fail to differentiate normally into functional haematopoietic cells. This results in replacement of the normal bone marrow by the leukaemic cells....

scholarly journals The Impact of [C16Pyr][Amp] on the Aggressiveness in Breast and Prostate Cancer Cell Lines

2020 ◽  
Vol 21 (24) ◽  
pp. 9584
Author(s):  
Filipa Quintela Vieira ◽  
Ângela Marques-Magalhães ◽  
Vera Miranda-Gonçalves ◽  
Ricardo Ferraz ◽  
Mónica Vieira ◽  
...  
Keyword(s):  
Ionic Liquid ◽  
Cell Viability ◽  
Cell Lines ◽  
Colony Formation ◽  
Therapeutic Agent ◽  
Prostate Cancer Cell ◽  
Molecular Level ◽  
Gene Expressions ◽  
Breast And Prostate Cancer ◽  
The Impact

Breast (BrCa) and prostate (PCa) cancers are the most common malignancies in women and men, respectively. The available therapeutic options for these tumors are still not curative and have severe side effects. Therefore, there is an urgent need for more effective antineoplastic agents. Herein, BrCa, PCa, and benign cell lines were treated with two ionic liquids and two quinoxalines and functional experiments were performed—namely cell viability, apoptosis, cytotoxicity, and colony formation assays. At the molecular level, an array of gene expressions encompassing several molecular pathways were used to explore the impact of treatment on gene expression. Although both quinoxalines and the ionic liquid [C2OHMIM][Amp] did not show any effect on the BrCa and PCa cell lines, [C16Pyr][Amp] significantly decreased cell viability and colony formation ability, while it increased the apoptosis levels of all cell lines. Importantly, [C16Pyr][Amp] was found to be more selective for cancer cells and less toxic than cisplatin. At the molecular level, this ionic liquid was also associated with reduced expression levels of CPT2, LDHA, MCM2, and SKP2, in both BrCa and PCa cell lines. Hence, [C16Pyr][Amp] was shown to be a promising anticancer therapeutic agent for BrCa and PCa cell lines.

The Polyphenolic Compound Curcumin Conjugation with an Alkyne Moiety in the Process of Autophagy

2018 ◽  
Vol 46 (03) ◽  
pp. 673-687 ◽  
Author(s):  
Peiyi Yan ◽  
Xin Sun ◽  
Xiaochen Chen ◽  
Yun Chen ◽  
Xiao Wang ◽  
...  
Keyword(s):  
Therapeutic Agent ◽  
Mammalian Target Of Rapamycin ◽  
Autophagic Flux ◽  
Cell Growth Inhibition ◽  
Polyphenolic Compound ◽  
Mouse Embryonic Fibroblasts ◽  
Curcumin Treatment ◽  
Embryonic Fibroblasts ◽  
Evolutionarily Conserved ◽  
Related Proteins

Curcumin is a hydrophobic polyphenol derived from turmeric: the rhizome of the herb Curcumalonga. Autophagy is an evolutionarily conserved process, in which cellular proteins and organelles are engulfed in autophagosome and then fuses with lysosome for degradation. Our previous study showed that Curcumin activates lysosome and induce autophagy through inhibition of AKT (protein kinase K, PKB)-mammalian target of rapamycin (mTOR) pathway. But whether Curucmin affects the fusion of autophagosome-lysosome is still not clear. Here, we used Curcumin-probe conjugation with an alkyne moiety to label mouse embryonic fibroblasts (MEFs) and found that Curcumin targets autophagy-related proteins, enhances autophagic flux and activates lysosome in cells. Moreover, Curcumin treatment promotes the fusion of autophasosome-lysosome in MEFs. Second, the enhanced fusion of autophagosome-lysosome is attributed to mTOR suppression. Third, blockage of the autophagosome-lysosome fusion leads to cell growth inhibition by Curcumin. Taken together, data from our study indicates the importance of the fusion of autophagosome-lysosome in Curcumin-induced autophagy, which may facilitate the development of Curcumin as a potential therapeutic agent for oxidative stress-related diseases.

scholarly journals Chromatin Accessibility Reveals Potential Prognostic Value of the Peak Set Associated with Smoking History in Patients with Lung Adenocarcinoma

2021 ◽  
Author(s):  
Han Liang ◽  
Jianlian Deng ◽  
Tian Luo ◽  
Huijuan Luo ◽  
Xuan Wu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Principal Component ◽  
Progression Free Survival ◽  
Chromatin Accessibility ◽  
Smoking History ◽  
Molecular Characteristics ◽  
Open Chromatin ◽  
Free Survival ◽  
Glycosphingolipid Biosynthesis ◽  
Chromatin Patterns

Abstract Considerable differences in molecular characteristics have been defined between non-smoker and smokers in patients with lung adenocarcinoma (LUAD), yet studies of open chromatin patterns associated with LUAD progression caused by smoking are still lacking. Here, we constructed a novel network based on correlations between each ATAC-seq peak from TCGA data using our previously developed algorithm. Subsequently, principal component analysis was performed on LUAD samples with retained peaks filtered by the correlation network and pathway analysis was conducted for potential pathways identification. We identified a set of peaks that discriminated smokers in LUAD patients according to levels of exposure to tobacco quantified in pack-years, and also significantly associated with progression-free survival and overall survival of these patients. We then investigated the gene set related to those peaks and found that the comprising genes are strongly associated with LUAD development, such as B3GNT3, ACTN4 and CLDN3. They are consistent with the important roles for the associated pathways in LUAD oncogenesis induced by smoking, including glycosphingolipid biosynthesis and tight junction pathways. In summary, our study may provide valuable insights on exploration of ATAC-seq peaks and on smoking-related LUAD carcinogenesis from a perspective of open chromatin changes.

Co-culture of carp (Cyprinus carpio) kidney haematopoietic cells with feeder cells resulting in long-term proliferation of T-cell lineages

2009 ◽  
Vol 131 (1-2) ◽  
pp. 127-136 ◽  
Author(s):  
Fumihiko Katakura ◽  
Fumio Takizawa ◽  
Miyuki Yoshida ◽  
Takuya Yamaguchi ◽  
Kyosuke Araki ◽  
...  
Keyword(s):  
T Cell ◽  
Cyprinus Carpio ◽  
Feeder Cells ◽  
Cell Lineages ◽  
Haematopoietic Cells ◽  
Carp Cyprinus Carpio

scholarly journals Valproic Acid: A Promising Therapeutic Agent in Glioma Treatment

2021 ◽  
Vol 11 ◽  
Author(s):  
Wei Han ◽  
Wei Guan
Keyword(s):  
Valproic Acid ◽  
Histone Deacetylase Inhibitors ◽  
Therapeutic Agent ◽  
Treatment Resistance ◽  
Progression Free Survival ◽  
Inhibitory Effects ◽  
Free Survival ◽  
Underlying Mechanisms

Glioma, characterized by infiltrative growth and treatment resistance, is regarded as the most prevalent intracranial malignant tumor. Due to its poor prognosis, accumulating investigation has been performed for improvement of overall survival (OS) and progression-free survival (PFS) in glioma patients. Valproic acid (VPA), one of the most common histone deacetylase inhibitors (HDACIs), has been detected to directly or synergistically exert inhibitory effects on glioma in vitro and in vivo. In this review, we generalize the latest advances of VPA in treating glioma and its underlying mechanisms and clinical implications, providing a clearer profile for clinical application of VPA as a therapeutic agent for glioma.

scholarly journals Chromatin Accessibility Reveals Potential Prognostic Value of the Peak Set Associated with Smoking History in Patients with Lung Adenocarcinoma

2021 ◽  
Author(s):  
Han Liang ◽  
Jianlian Deng ◽  
Tian Luo ◽  
Huijuan Luo ◽  
Xuan Wu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Principal Component ◽  
Progression Free Survival ◽  
Chromatin Accessibility ◽  
Smoking History ◽  
Molecular Characteristics ◽  
Open Chromatin ◽  
Free Survival ◽  
Glycosphingolipid Biosynthesis ◽  
Chromatin Patterns

Abstract Considerable differences in molecular characteristics have been defined between non-smoker and smokers in patients with lung adenocarcinoma (LUAD), yet studies of open chromatin patterns associated with LUAD progression caused by smoking are still lacking. Here, we constructed a novel network based on correlations between each ATAC-seq peak from TCGA data using our previously developed algorithm. Subsequently, principal component analysis was performed on LUAD samples with retained peaks filtered by the correlation network and pathway analysis was conducted for potential pathways identification. We identified a set of peaks that discriminated smokers in LUAD patients according to levels of exposure to tobacco quantified in pack-years, and also significantly associated with progression-free survival and overall survival of these patients. We then investigated the gene set related to those peaks and found that the comprising genes are strongly associated with LUAD development, such as B3GNT3, ACTN4 and CLDN3. They are consistent with the important roles for the associated pathways in LUAD oncogenesis induced by smoking, including glycosphingolipid biosynthesis and tight junction pathways. In summary, our study may provide valuable insights on exploration of ATAC-seq peaks and on smoking-related LUAD carcinogenesis from a perspective of open chromatin changes.

scholarly journals Repurposing Itraconazole Loaded PLGA Nanoparticles for Improved Antitumor Efficacy in Non-Small Cell Lung Cancers

Pharmaceutics ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 685 ◽  
Author(s):  
Nabil A. Alhakamy ◽  
Shadab Md
Keyword(s):  
Cancer Cells ◽  
Therapeutic Agent ◽  
Water Solubility ◽  
Molecular Level ◽  
Controlled Drug Release ◽  
Plga Nanoparticles ◽  
Anticancer Activities ◽  
Drug Release Profile ◽  
Lung Cancers ◽  
Bcl2 Protein

Itraconazole (ITR) is a broad-spectrum antifungal drug, which has been shown to possess some promising anticancer, anti-proliferative, and anti-angiogenic properties in some cancers, such as cancers of the lung, breast, and skin. However, ITR has some drawbacks, such as poor water solubility, which hinder its use as a therapeutic agent. Therefore, in the present study, we developed and characterized chitosan-coated PLGA nanoparticles of itraconazole and studied their anticancer activities in H1299 lung cancer cells. The prepared ITR nanoparticles showed a small particle size, narrow poly dispersity index (PDI), positive zeta potential, and a controlled drug release profile. The cytotoxicity of ITR nanoparticles (NPs) on H1299 cancer cells after 24 h of exposure was greater than that of the ITR solution. Apoptosis of cancer cells exposed to ITR nanoparticles was also enhanced in comparison with the ITR solution. At the molecular level, ITR NPs were more effective than ITR solution in inducing pro-apoptotic Bax and p53 while reducing anti-apoptotic Bcl2 protein expression. ITR NPs were more effective than ITR solution in arresting cells both at the G0/G1 as well as G2/M phases of the cell cycle. Hence, repurposing itraconazole by encapsulation into PLGA NPs with chitosan coating is a potentially promising approach to treat lung cancers.

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