Growth inhibition of human osteosarcoma HuO9 cells by methylglyoxal bis(cyclopentylamidinohydrazone) in vitro and in vivo.

1999 ◽  
Author(s):  
N Satoh ◽  
H Hibasami ◽  
K Mori ◽  
H Kaneko ◽  
H Wakabayashi ◽  
...  
Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1250-1255 ◽  
Author(s):  
S Whitehead ◽  
TE Peto

Abstract Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Siamak Salehi ◽  
Oliver D. Tavabie ◽  
Augusto Villanueva ◽  
Julie Watson ◽  
David Darling ◽  
...  

AbstractRegulated cell proliferation is an effector mechanism of regeneration, whilst dysregulated cell proliferation is a feature of cancer. We have previously identified microRNA (miRNA) that regulate successful and failed human liver regeneration. We hypothesized that these regulators may directly modify tumor behavior. Here we show that inhibition of miRNAs -503 and -23a, alone or in combination, enhances tumor proliferation in hepatocyte and non-hepatocyte derived cancers in vitro, driving more aggressive tumor behavior in vivo. Inhibition of miRNA-152 caused induction of DNMT1, site-specific methylation with associated changes in gene expression and in vitro and in vivo growth inhibition. Enforced changes in expression of two miRNA recapitulating changes observed in failed regeneration led to complete growth inhibition of multi-lineage cancers in vivo. Our results indicate that regulation of regeneration and tumor aggressiveness are concordant and that miRNA-based inhibitors of regeneration may constitute a novel treatment strategy for human cancers.


Author(s):  
Letizia Mondani ◽  
Giorgio Chiusa ◽  
Paola Battilani

AbstractThe aim of the study was to test in vitro and in vivo the efficacy of triazoles and biocontrol agents (BCAs) against Fusarium proliferatum and F. oxysporum, the former signaled as the main causal agent of garlic dry rot and the latter also involved. In vitro trials were organized using potato dextrose agar with added chemicals or BCAs inoculated with selected F. proliferatum and F. oxysporum. Garlic cloves were dipped before sowing in suspensions prepared with the fungicides showing the best performances in vitro; then they were dipped in Fusaria suspension before sowing. In in vitro trials, the maximum Fusaria growth inhibition was performed by Propiconazole + Prochloraz (100%), followed by Tebuconazole (88.9%). BCAs showed great capacity to control Fusaria, with a maximum growth inhibition of 80% (Trichoderma harzianum + T. gamsii). In vivo bacterial BCAs showed a similar capacity to control F. proliferatum and F. oxysporum compared to chemical products (mean of severity index 18.6% and 11.7%, respectively). In vivo results confirmed the in vitro performances, except for Trichoderma, which had the worst performances in vivo. Therefore, the results are preliminary but promising for future field application.


npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Rachel Tanner ◽  
Andrew D. White ◽  
Charelle Boot ◽  
Claudia C. Sombroek ◽  
Matthew K. O’Shea ◽  
...  

AbstractWe present a non-human primate mycobacterial growth inhibition assay (MGIA) using in vitro blood or cell co-culture with the aim of refining and expediting early tuberculosis vaccine testing. We have taken steps to optimise the assay using cryopreserved peripheral blood mononuclear cells, transfer it to end-user institutes, and assess technical and biological validity. Increasing cell concentration or mycobacterial input and co-culturing in static 48-well plates compared with rotating tubes improved intra-assay repeatability and sensitivity. Standardisation and harmonisation efforts resulted in high consistency agreements, with repeatability and intermediate precision <10% coefficient of variation (CV) and inter-site reproducibility <20% CV; although some systematic differences were observed. As proof-of-concept, we demonstrated ability to detect a BCG vaccine-induced improvement in growth inhibition in macaque samples, and a correlation between MGIA outcome and measures of protection from in vivo disease development following challenge with either intradermal BCG or aerosol/endobronchial Mycobacterium tuberculosis (M.tb) at a group and individual animal level.


2011 ◽  
Vol 15 (03) ◽  
pp. 174-180 ◽  
Author(s):  
Lan Ying Wen ◽  
Su-Mi Bae ◽  
Jin Hwan Do ◽  
Kye-Shin Park ◽  
Woong Shick Ahn

Photodynamic therapy (PDT) is a promising treatment for cancer that has been recently accepted in the clinic. In this study, we examined a biological significance of PDT with a chlorin-based photosensitizer, Photodithazine, on cervical cancer model. When human papillomavirus type 16 (HPV16)- transformed mouse TC-1 cells were exposed to varied doses of Photodithazine with light irradiation (6.25 J/cm2), the significant growth inhibition of TC-1 cells was observed at 0.75 μg/mL of Photodithazine. The damaged cells by Photodithazine/PDT were categorized to be early and late apoptosis, as determined by annexin V staining. Photodithazine was primarily localized at lysosome apparatus within TC-1 cells while it was rapidly accumulated and sustained for initial 3 h in tumor tissue of TC-1 tumor bearing mice after IV injection. The tumor growth inhibition by Photodithazine/PDT with light irradiation (300 J/cm2) was examined after injection of various concentration of Photodithazine in tumor mice system. Our results show that Photodithazine/PDT might have significant advantages in the selective killing of tumor lesions in HPV 16 E6/E7 associated cervical cancer model, both in vitro and in vivo.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1844-1844
Author(s):  
John Richards ◽  
Myriam N Bouchlaka ◽  
Robyn J Puro ◽  
Ben J Capoccia ◽  
Ronald R Hiebsch ◽  
...  

AO-176 is a highly differentiated, humanized anti-CD47 IgG2 antibody that is unique among agents in this class of checkpoint inhibitors. AO-176 works by blocking the "don't eat me" signal, the standard mechanism of anti-CD47 antibodies, but also by directly killing tumor cells. Importantly, AO-176 binds preferentially to tumor cells, compared to normal cells, and binds even more potently to tumors in their acidic microenvironment (low pH). Hematological neoplasms are the fourth most frequently diagnosed cancers in both men and women and account for approximately 10% of all cancers. Here we describe AO-176, a highly differentiated anti-CD47 antibody that potently targets hematologic cancers in vitro and in vivo. As a single agent, AO-176 not only promotes phagocytosis (15-45%, EC50 = 0.33-4.1 µg/ml) of hematologic tumor cell lines (acute myeloid leukemia, non-Hodgkin's lymphoma, multiple myeloma, and T cell leukemia) but also directly targets and kills tumor cells (18-46% Annexin V positivity, EC50 = 0.63-10 µg/ml) in a non-ADCC manner. In combination with agents targeting CD20 (rituximab) or CD38 (daratumumab), AO-176 mediates enhanced phagocytosis of lymphoma and multiple myeloma cell lines, respectively. In vivo, AO-176 mediates potent monotherapy tumor growth inhibition of hematologic tumors including Raji B cell lymphoma and RPMI-8226 multiple myeloma xenograft models in a dose-dependent manner. Concomitant with tumor growth inhibition, immune cell infiltrates were observed with elevated numbers of macrophage and dendritic cells, along with increased pro-inflammatory cytokine levels in AO-176 treated animals. When combined with bortezomib, AO-176 was able to elicit complete tumor regression (100% CR in 10/10 animals treated with either 10 or 25 mg/kg AO-176 + 1 mg/kg bortezomib) with no detectable tumor out to 100 days at study termination. Overall survival was also greatly improved following combination therapy compared to animals treated with bortezomib or AO-176 alone. These data show that AO-176 exhibits promising monotherapy and combination therapy activity, both in vitro and in vivo, against hematologic cancers. These findings also add to the previously reported anti-tumor efficacy exhibited by AO-176 in solid tumor xenografts representing ovarian, gastric and breast cancer. With AO-176's highly differentiated MOA and binding characteristics, it may have the potential to improve upon the safety and efficacy profiles relative to other agents in this class. AO-176 is currently being evaluated in a Phase 1 clinical trial (NCT03834948) for the treatment of patients with select solid tumors. Disclosures Richards: Arch Oncology Inc.: Employment, Equity Ownership, Other: Salary. Bouchlaka:Arch Oncology Inc.: Consultancy, Equity Ownership. Puro:Arch Oncology Inc.: Employment, Equity Ownership. Capoccia:Arch Oncology Inc.: Employment, Equity Ownership. Hiebsch:Arch Oncology Inc.: Employment, Equity Ownership. Donio:Arch Oncology Inc.: Employment, Equity Ownership. Wilson:Arch Oncology Inc.: Employment, Equity Ownership. Chakraborty:Arch Oncology Inc.: Employment, Equity Ownership. Sung:Arch Oncology Inc.: Employment, Equity Ownership. Pereira:Arch Oncology Inc.: Employment, Equity Ownership.


2002 ◽  
Vol 13 (5) ◽  
pp. 533-543 ◽  
Author(s):  
Jane-Jen Wang ◽  
Yaw-Terng Chern ◽  
Yuh-Fang Chang ◽  
Tsung-Yun Liu ◽  
Chin-Wen Chi

2020 ◽  
Vol 12 (8) ◽  
pp. 1022-1029
Author(s):  
Ming Liu ◽  
Chen Lin ◽  
Xiaoqing Huang ◽  
Yuxiang Lin

Natural flavonoid formononetin (FN) has anticancer effects, but the hydrophobic structure, characteristics of the short half-life in vivo, limiting its clinical wide-ranging application. In this study, FN loaded Pluronic (PF)@folic acid (FA) micelles (FN-PF@FA), were prepared to improve the solubility, bioavailability and targeting. FA coupling PF was prepared by carbodiimide crosslinker chemical method, FN-PF@FA micelles were prepared by modified film hydration method, and compared the antitumor activity of FN loaded micelles with free FN In Vitro. The spherical smooth surface of FN-PF@FA micelles had smaller particle size (112.3±5.3 nm), high encapsulation efficiency (86.14±2.68%), high negative zeta potential (-25.8±0.57 mV), low critical concentration CMC (0.03 mg/mL), and better sustained release profile. In addition, FN-PF@FA micelles have a positive targeting effect on oral squamous cell carcinoma cells (SCC3). In 48 hours, the growth inhibition of 50% (GI50) was 28.6±1.2 μg/mL for FN and 17.4±0.78 μg/mL for FN-PF, the dose dropped by nearly 38.46%. In addition, the GI50 value of FN-PF@FA was 9.5±0.3 μg/mL, 66.43% lower than FN and 44.83% lower than FN-PF. Furthermore, the laser scanning confocal microscopy revealed that the conjugation of FA significantly improves the active targeting ability of micelles. FN-PF@FA micelles have the potential to target the release of anticancer drugs with higher bioavailability, further provides a new avenue for the application of traditional Chinese medicine extract in oral malignant tumor.


2019 ◽  
Vol 83 (4) ◽  
pp. 681-692 ◽  
Author(s):  
Maria Carolina Ruiz ◽  
Agustina Resasco ◽  
Ana Laura Di Virgilio ◽  
Miguel Ayala ◽  
Isabel Cavaco ◽  
...  

Antibiotics ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 894
Author(s):  
Vanessa Raquel Greatti ◽  
Fernando Oda ◽  
Rodrigo Sorrechia ◽  
Bárbara Regina Kapp ◽  
Carolina Manzato Seraphim ◽  
...  

Dermatophyte fungal infections are difficult to treat because they need long-term treatments. 4-Nerolidylcatechol (4-NC) is a compound found in Piper umbellatum that has been reported to demonstrate significant antifungal activity, but is easily oxidizable. Due to this characteristic, the incorporation in nanostructured systems represents a strategy to guarantee the compound’s stability compared to the isolated form and the possibility of improving antifungal activity. The objective of this study was to incorporate 4-NC into polymeric nanoparticles to evaluate, in vitro and in vivo, the growth inhibition of Microsporum canis. 4-NC was isolated from fresh leaves of P. umbellatum, and polymer nanoparticles of polycaprolactone were developed by nanoprecipitation using a 1:5 weight ratio (drug:polymer). Nanoparticles exhibited excellent encapsulation efficiency, and the antifungal activity was observed in nanoparticles with 4-NC incorporated. Polymeric nanoparticles can be a strategy employed for decreased cytotoxicity, increasing the stability and solubility of substances, as well as improving the efficacy of 4-NC.


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