Direct Readout Hypoxia Tumor Suppression In Vivo through NIR-Theranostic Activation

2021 ◽  
Author(s):  
Yu-Qiang Zhao ◽  
Shayeri Biswas ◽  
Qiuling Chen ◽  
Mingxuan Jia ◽  
Ying Zhou ◽  
...  
Keyword(s):  
Tumor Suppression ◽  
Direct Readout

scholarly journals A novel dual-prodrug carried by cyclodextrin inclusion complex for the targeting treatment of colon cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lin Chen ◽  
Yan Lin ◽  
Zijun Zhang ◽  
Ruisheng Yang ◽  
Xiaosheng Bai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Ulcerative Colitis ◽  
Colon Cancer ◽  
Inclusion Complex ◽  
Tumor Suppression ◽  
Folate Receptor ◽  
Significant Inhibition ◽  
Aminosalicylic Acid ◽  
Anti Inflammatory

Abstract Background There is an obvious correlation between ulcerative colitis and colorectal cancer, and the risk of colorectal cancer in patients with ulcerative colitis is increasing. Therefore, the combination therapy of anti-inflammatory and anti-tumor drugs may show promising to inhibit colon cancer. 5-aminosalicylic acid (5-ASA) with anti-inflammatory function is effective for maintaining remission in patients with ulcerative colitis and may also reduce colorectal cancer risk. Histone deacetylase (HDAC) plays an essential role in the progression of colon cancer. Butyric acid (BA) is a kind of HDAC inhibitor and thus shows tumor suppression to colon cancer. However, the volatile and corrosive nature of BA presents challenges in practical application. In addition, its clinical application is limited due to its non-targeting ability and low bioavailability. We aimed to synthesize a novel dual-prodrug of 5-ASA and BA, referred as BBA, to synergistically inhibit colon cancer. Further, based on the fact that folate receptor (FR) is over-expressed in most solid tumors and it has been identified to be a cancer stem cell surface marker in colon cancer, we took folate as the targeting ligand and used carboxymethyl-β-cyclodextrin (CM-β-CD) to carry BBA and thus prepared a novel inclusion complex of BBA/FA-PEG-CM-β-CD. Results It was found that BBA/FA-PEG-CM-β-CD showed significant inhibition in cell proliferation against colon cancer cells SW620. It showed a pro-longed in vivo circulation and mainly accumulated in tumor tissue. More importantly, BBA/FA-PEG-CM-β-CD gave great tumor suppression effect against nude mice bearing SW620 xenografts. Conclusions Therefore, BBA/FA-PEG-CM-β-CD may have clinical potential in colon cancer therapy. Graphical Abstract

scholarly journals p53 DNA Binding Cooperativity Is Essential for Apoptosis and Tumor Suppression In Vivo

Cell Reports ◽  
2013 ◽  
Vol 3 (5) ◽  
pp. 1512-1525 ◽  
Author(s):  
Oleg Timofeev ◽  
Katharina Schlereth ◽  
Michael Wanzel ◽  
Attila Braun ◽  
Bernhard Nieswandt ◽  
...  
Keyword(s):  
Dna Binding ◽  
Tumor Suppression

scholarly journals The Circadian Gene Period2 Plays an Important Role in Tumor Suppression and DNA-Damage Response In Vivo

Cell ◽  
2002 ◽  
Vol 111 (7) ◽  
pp. 1055 ◽  
Author(s):  
Loning Fu ◽  
Helene Pelicano ◽  
Jinsong Liu ◽  
Peng Huang ◽  
Cheng Chi Lee
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Tumor Suppression ◽  
Circadian Gene ◽  
Damage Response

Tumor hnmunity: Tumor Suppression in vivo Initiated by Soluble Products of Specifically Stimulated Lymphocytes

Science ◽  
1971 ◽  
Vol 172 (3984) ◽  
pp. 729-731 ◽  
Author(s):  
I. D. Bernstein ◽  
D. E. Thor ◽  
B. Zbar ◽  
H. J. Rapp
Keyword(s):  
Tumor Suppression

scholarly journals In vivo tumor suppression activity by T cell-specific T-bet restoration

2010 ◽  
Vol 127 (9) ◽  
pp. 2129-2137 ◽  
Author(s):  
Kihyun Lee ◽  
Hyun Jung Min ◽  
Eun Jung Jang ◽  
Jeong-Ho Hong ◽  
Eun Sook Hwang
Keyword(s):  
T Cell ◽  
Tumor Suppression

scholarly journals Unmet Expectations: miR-34 Plays No Role in p53-Mediated Tumor Suppression In Vivo

PLoS Genetics ◽  
2012 ◽  
Vol 8 (7) ◽  
pp. e1002859 ◽  
Author(s):  
Abhinav K Jain ◽  
Michelle Craig Barton
Keyword(s):  
Tumor Suppression ◽  
Unmet Expectations

scholarly journals Intrinsic Cooperation between p16INK4a and p21Waf1/Cip1 in the Onset of Cellular Senescence and Tumor Suppression In vivo

2010 ◽  
Vol 70 (22) ◽  
pp. 9381-9390 ◽  
Author(s):  
Shinji Takeuchi ◽  
Akiko Takahashi ◽  
Noriko Motoi ◽  
Shin Yoshimoto ◽  
Tomoko Tajima ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Tumor Suppression

scholarly journals Anti-tumor effect of polysaccharide from Pleurotus ostreatus on H22 mouse Hepatoma ascites in-vivo and hepatocellular carcinoma in-vitro model

AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kavish Hasnain Khinsar ◽  
Sattar Abdul ◽  
Akbar Hussain ◽  
Riaz Ud Din ◽  
Liu Lei ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gene Regulation ◽  
Side Effects ◽  
Tumor Suppression ◽  
Pleurotus Ostreatus ◽  
Edible Mushroom ◽  
Malignant Ascites ◽  
In Vivo Model

AbstractHepatocellular carcinoma is one of the leading causes of cancer-associated death across the globe. Malignant ascites are the major clinical attributes in cancer patients. Despite the advancements in HCC treatments such as chemotherapy, radiotherapy, surgery, and hormonal therapy, researchers are pursuing novel natural edible compounds for the treatment of cancer to eliminate dreadful side effects. Pleurotus ostreatus is one of the most edible cuisines in Asia as well as all over the world. It has been a source of nutritious diet since it was classified as an edible mushroom with no or negligible side effects. The present study focused on the natural anti-cancerous and anti-ascites capabilities of polysaccharides extracted from Pleurotus ostreatus in-vivo as well as in-vitro. Administration of polysaccharide Pleurotus ostreatus showed a significant decrease in tumor cell metastasis while the increase in the survival period among mice models of H22 malignant ascites. Downregulation of regenerative genes Foxp3 and Stat3 and secretion of immunological factors such as IL-2, TNF α, and INF γ were observed after treating with the partially pure extracted polysaccharide. Twining with the hypothesis of tumor suppression in-vivo model polysaccharide showed a decrease in invasion and migration abilities and henceforth responsible for the gene regulation such Cytochrome C which supposedly induced the chain of gene regulation process resulting in apoptosis in HCC cell lines observed in-vitro experiments. Collective research findings manifested that polysaccharide extracted from Pleurotus ostreatus bears anti-proliferative activity and thus influence tumor suppression in-vivo and in-vitro against hepatocellular carcinoma and can be used for therapeutic purposes as a potential anti-cancerous source in the future.

scholarly journals In vivo evaluation of CD38 and CD138 as targets for nanoparticle-based drug delivery in multiple myeloma

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
David T. Omstead ◽  
Franklin Mejia ◽  
Jenna Sjoerdsma ◽  
Baksun Kim ◽  
Jaeho Shin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Tumor Suppression ◽  
Synthetic Methods ◽  
Cell Uptake ◽  
In Vivo Evaluation ◽  
Targeted Nanoparticles ◽  
Liposomal Nanoparticles ◽  
Tumor Accumulation

Abstract Background Drug-loaded nanoparticles have established their benefits in the fight against multiple myeloma; however, ligand-targeted nanomedicine has yet to successfully translate to the clinic due to insufficient efficacies reported in preclinical studies. Methods In this study, liposomal nanoparticles targeting multiple myeloma via CD38 or CD138 receptors are prepared from pre-synthesized, purified constituents to ensure increased consistency over standard synthetic methods. These nanoparticles are then tested both in vitro for uptake to cancer cells and in vivo for accumulation at the tumor site and uptake to tumor cells. Finally, drug-loaded nanoparticles are tested for long-term efficacy in a month-long in vivo study by tracking tumor size and mouse health. Results The targeted nanoparticles are first optimized in vitro and show increased uptake and cytotoxicity over nontargeted nanoparticles, with CD138-targeting showing superior enhancement over CD38-targeted nanoparticles. However, biodistribution and tumor suppression studies established CD38-targeted nanoparticles to have significantly increased in vivo tumor accumulation, tumor cell uptake, and tumor suppression over both nontargeted and CD138-targeted nanoparticles due to the latter’s poor selectivity. Conclusion These results both highlight a promising cancer treatment option in CD38-targeted nanoparticles and emphasize that targeting success in vitro does not necessarily translate to success in vivo.

scholarly journals Caveolin-1-Mediated Tumor Suppression Is Linked to Reduced HIF1α S-Nitrosylation and Transcriptional Activity in Hypoxia

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2349
Author(s):  
Carlos Sanhueza ◽  
Jimena Castillo Bennett ◽  
Manuel Valenzuela-Valderrama ◽  
Pamela Contreras ◽  
Lorena Lobos-González ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Tumor Suppression ◽  
Transcriptional Activity ◽  
Nuclear Translocation ◽  
Caveolin 1 ◽  
Oxide Synthase ◽  
E Cadherin

Caveolin-1 (CAV1) is a well-established nitric oxide synthase inhibitor, whose function as a tumor suppressor is favored by, but not entirely dependent on, the presence of E-cadherin. Tumors are frequently hypoxic and the activation of the hypoxia-inducible factor-1α (HIF1α) promotes tumor growth. HIF1α is regulated by several post-translational modifications, including S-nitrosylation. Here, we evaluate the mechanisms underlying tumor suppression by CAV1 in cancer cells lacking E-cadherin in hypoxia. Our main findings are that CAV1 reduced HIF activity and Vascular Endothelial Growth Factor expression in vitro and in vivo. This effect was neither due to reduced HIF1α protein stability or reduced nuclear translocation. Instead, HIF1α S-nitrosylation observed in hypoxia was diminished by the presence of CAV1, and nitric oxide synthase (NOS) inhibition by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) reduced HIF1α transcriptional activity in cells to the same extent as observed upon CAV1 expression. Additionally, arginase inhibition by (S)-(2-Boronoethyl)-L-cysteine (BEC) partially rescued cells from the CAV1-mediated suppression of HIF1α transcriptional activity. In vivo, CAV1-mediated tumor suppression was dependent on NOS activity. In summary, CAV1-dependent tumor suppression in the absence of E-cadherin is linked to reduced HIF1α transcriptional activity via diminished NOS-mediated HIF1α S-nitrosylation.

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