scholarly journals Novel Selectively Targeted Multifunctional Nanostructured Lipid Carriers for Prostate Cancer Treatment

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 88
Author(s):  
Lital Cohen ◽  
Yehuda G. Assaraf ◽  
Yoav D. Livney
Keyword(s):  
Prostate Cancer ◽  
Time Course ◽  
Average Diameter ◽  
Nanostructured Lipid Carriers ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Selective Ligand ◽  
Delivery Platform ◽  
Dependent Growth

Prostate cancer (PC) is the most common cancer in men over 50 and the 4th most prevalent human malignancy. PC treatment may include surgery, androgen deprivation therapy, chemotherapy, and radiation therapy. However, the therapeutic efficacy of systemic chemotherapy is limited due to low drug solubility and insufficient tumor specificity, inflicting toxic side effects and frequently provoking the emergence of drug resistance. Towards the efficacious treatment of PC, we herein developed novel selectively PC-targeted nanoparticles (NPs) harboring a cytotoxic drug cargo. This delivery system is based upon PEGylated nanostructured lipid carriers (NLCs), decorated with a selective ligand, targeted to prostate-specific membrane antigen (PSMA). NPs loaded with cabazitaxel (CTX) displayed a remarkable loading capacity of 168 ± 3 mg drug/g SA-PEG, encapsulation efficiency of 67 ± 1%, and an average diameter of 159 ± 3 nm. The time-course of in vitro drug release from NPs revealed a substantial drug retention profile compared to the unencapsulated drug. These NPs were selectively internalized into target PC cells overexpressing PSMA, and displayed a dose-dependent growth inhibition compared to cells devoid of the PSMA receptor. Remarkably, these targeted NPs exhibited growth-inhibitory activity at pM CTX concentrations, being markedly more potent than the free drug. This selectively targeted nano-delivery platform bears the promise of enhanced efficacy and minimal untoward toxicity.

scholarly journals Semi-Synthesis of Harringtonolide Derivatives and Their Antiproliferative Activity

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1380
Author(s):  
Xiutao Wu ◽  
Lijie Gong ◽  
Chen Chen ◽  
Ye Tao ◽  
Wuxi Zhou ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Normal Cell ◽  
Selectivity Index ◽  
Cytotoxic Activities ◽  
Structure Activity ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Hct 116 ◽  
Systematic Structure

Harringtonolide (HO), a natural product isolated from Cephalotaxus harringtonia, exhibits potent antiproliferative activity. However, little information has been reported on the systematic structure−activity relationship (SAR) of HO derivatives. Modifications on tropone, lactone, and allyl positions of HO (1) were carried out to provide 17 derivatives (2–13, 11a–11f). The in vitro antiproliferative activity against four cancer cell lines (HCT-116, A375, A549, and Huh-7) and one normal cell line (L-02) was tested. Amongst these novel derivatives, compound 6 exhibited comparable cell growth inhibitory activity to HO and displayed better selectivity index (SI = 56.5) between Huh-7 and L-02 cells. The SAR results revealed that the tropone and lactone moieties are essential for the cytotoxic activities, which provided useful suggestions for further structural optimization of HO.

scholarly journals Plasmodium falciparum Line-Dependent Association ofIn VitroGrowth-Inhibitory Activity and Risk of Malaria

2012 ◽  
Vol 80 (5) ◽  
pp. 1900-1908 ◽  
Author(s):  
Josea Rono ◽  
Anna Färnert ◽  
Daniel Olsson ◽  
Faith Osier ◽  
Ingegerd Rooth ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Inhibitory Activity ◽  
Content Type ◽  
Phenotypic Differences ◽  
Erythrocyte Invasion ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Control Study

ABSTRACTPlasmodium falciparum's ability to invade erythrocytes is essential for its survival within the human host. Immune mechanisms that impair this ability are therefore expected to contribute to immunity against the parasite. Plasma of humans who are naturally exposed to malaria has been shown to have growth-inhibitory activity (GIA)in vitro. However, the importance of GIA in relation to protection from malaria has been unclear. In a case-control study nested within a longitudinally followed population in Tanzania, plasma samples collected at baseline from 171 individuals (55 cases and 116 age-matched controls) were assayed for GIA using threeP. falciparumlines (3D7, K1, and W2mef) chosen based on their erythrocyte invasion phenotypes. Distribution of GIA differed between the lines, with most samples inhibiting the growth of 3D7 and K1 and enhancing the growth of W2mef. GIA to 3D7 was associated with a reduced risk of malaria within 40 weeks of follow-up (odds ratio, 0.45; 95% confidence interval [CI], 0.21 to 0.96;P= 0.04), whereas GIA to K1 and W2mef was not. These results show that GIA, as well as its association with protection from malaria, is dependent on theP. falciparumline and can be explained by differences in erythrocyte invasion phenotypes between parasite lines. Our study contributes knowledge on the biological importance of growth inhibition and the potential influence ofP. falciparumerythrocyte invasion phenotypic differences on its relationship to protective immunity against malaria.

scholarly journals Anti-Trypanosomal Alkaloids from Xymalos Monospora

2006 ◽  
Vol 1 (8) ◽  
pp. 1934578X0600100
Author(s):  
Dieudonne Ngamga ◽  
Pierre Tane ◽  
Donna Rattendi ◽  
Cyrus Bacchi ◽  
Christopher C. Okunji ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Stem Bark ◽  
Aporphine Alkaloid ◽  
African Trypanosomes ◽  
Benzylisoquinoline Alkaloids ◽  
Benzylisoquinoline Alkaloid ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity

From an extract of the stem bark of Xymalos monospora, a bis-benzylisoquinoline alkaloid (1), three benzylisoquinoline alkaloids (mollinedine, 1-(p-methoxybenzyl)-6,7-methylenedioxyisoquino-line, doryafranine), and an aporphine alkaloid (N-methyllaurotetanine) were isolated. These compounds were tested for growth inhibitory activity against bloodstream forms of three strains of African trypanosomes. In vitro IC50 values starting from 1.8 μg /mL were obtained.

scholarly journals Prospective study on the effect of short-term androgen deprivation therapy on PSMA uptake evaluated with 68Ga-PSMA-11 PET/MRI in men with treatment-naïve prostate cancer

2019 ◽  
Vol 47 (3) ◽  
pp. 665-673 ◽  
Author(s):  
Otto Ettala ◽  
Simona Malaspina ◽  
Terhi Tuokkola ◽  
Pauliina Luoto ◽  
Eliisa Löyttyniemi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Androgen Deprivation Therapy ◽  
Time Course ◽  
Specific Antigen ◽  
Androgen Deprivation ◽  
Short Term ◽  
Psma Pet ◽  
Treatment Naïve

Abstract Purpose Based on in vitro studies, it is known that androgen deprivation therapy (ADT) increases prostate-specific membrane antigen (PSMA) expression. Therefore, we hypothesised that ADT improves the performance of PSMA-PET imaging in primary staging of prostate cancer. The purpose of the study was to demonstrate the time course effect of ADT on PSMA uptake in different types of metastatic lesions evaluated with 68Ga-PSMA-11 PET/MRI. Methods Nine men with treatment-naïve prostate cancer were enrolled to a prospective, registered (NCT03313726) clinical trial. A 68Ga-PSMA-11 PET/MRI was performed once before and 3 times post-ADT (degarelix, Firmagon). Change of maximum standardised uptake values (SUVmax) in prostate, lymph nodes, bone metastases, and physiologically PSMA-avid organs were evaluated in a time frame of 1–8 weeks. Results All patients reached castration levels within 10 days, and 50% decrease in prostate-specific antigen (PSA) concentration was observed 14 days post-ADT. A heterogeneous increase in PSMA uptake was observed 3 to 4 weeks post-ADT. This phenomenon was definitively more evident in bone metastases: 13 (57%) of the metastasis, with a mean (range) SUVmax increase of 77% (8–238%). In one patient, already having bone metastases at baseline, three new bone metastases were observed post-ADT. Of lesions with reduced SUVmax, none disappeared. Conclusions Both in patient and region level, increase in PSMA uptake post-ADT is heterogenous and is seen most evidently in bone metastases. Preliminary results on a small cohort of patients suggest the clinical impact of ADT on improving the performance of 68Ga-PSMA PET in staging seems to be minor. However, the optimal imaging time point might be 3 to 4 weeks post-ADT. Since none of the metastases with decreasing SUVmax disappeared, it seems that short-term usage of ADT does not interfere with the interpretation of 68Ga-PSMA PET. Trial registration NCT03313726, registered 18 October 2017; EUDRA-CT, 2017-002345-29.

scholarly journals In Vitro Growth-Inhibitory Activity and Malaria Risk in a Cohort Study in Mali

2009 ◽  
Vol 78 (2) ◽  
pp. 737-745 ◽  
Author(s):  
Peter D. Crompton ◽  
Kazutoyo Miura ◽  
Boubacar Traore ◽  
Kassoum Kayentao ◽  
Aissata Ongoiba ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Vaccine Development ◽  
Critical Role ◽  
Malaria Risk ◽  
Activity Level ◽  
Asexual Blood Stage ◽  
Growth Inhibition Assay ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity

ABSTRACT Immunity to the asexual blood stage of Plasmodium falciparum is complex and likely involves several effector mechanisms. Antibodies are thought to play a critical role in malaria immunity, and a corresponding in vitro correlate of antibody-mediated immunity has long been sought to facilitate malaria vaccine development. The growth inhibition assay (GIA) measures the capacity of antibodies to limit red blood cell (RBC) invasion and/or growth of P. falciparum in vitro. In humans, naturally acquired and vaccine-induced P. falciparum-specific antibodies have growth-inhibitory activity, but it is unclear if growth-inhibitory activity correlates with protection from clinical disease. In a longitudinal study in Mali, purified IgGs, obtained from plasmas collected before the malaria season from 220 individuals aged 2 to 10 and 18 to 25 years, were assayed for growth-inhibitory activity. Malaria episodes were recorded by passive surveillance over the subsequent 6-month malaria season. Logistic regression showed that greater age (odds ratio [OR], 0.78; 95% confidence interval [95% CI], 0.63 to 0.95; P = 0.02) and growth-inhibitory activity (OR, 0.50; 95% CI, 0.30 to 0.85; P = 0.01) were significantly associated with decreased malaria risk in children. A growth-inhibitory activity level of 40% was determined to be the optimal cutoff for discriminating malaria-immune and susceptible individuals in this cohort, with a sensitivity of 97.0%, but a low specificity of 24.3%, which limited the assay's ability to accurately predict protective immunity and to serve as an in vitro correlate of antibody-mediated immunity. These data suggest that antibodies which block merozoite invasion of RBC and/or inhibit the intra-RBC growth of the parasite contribute to but are not sufficient for the acquisition of malaria immunity.

scholarly journals Specific growth inhibitory sequences in genomic DNA from quiescent human embryo fibroblasts.

1987 ◽  
Vol 7 (5) ◽  
pp. 1894-1899 ◽  
Author(s):  
R Padmanabhan ◽  
T H Howard ◽  
B H Howard
Keyword(s):  
Dna Sequences ◽  
Hela Cells ◽  
Human Embryo ◽  
Inhibitory Activity ◽  
Genomic Dna ◽  
Molecular Mechanisms ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Embryo Fibroblasts

We used HeLa cells as recipients in a gene transfer assay to characterize DNA sequences that negatively regulate mammalian cell growth. In this assay, genomic DNA from quiescent human embryo fibroblasts was more inhibitory for HeLa replication than was DNA from either Escherichia coli or HeLa cells. Surprisingly, growth inhibitory activity depended on the growth state of the cells from which genomic DNA was prepared; it was strongest in DNA prepared from serum-deprived, quiescent embryo fibroblasts. This latter observation implies a role for DNA modification(s) in regulating the activity of the inhibitory sequences detected in our assay. The level of the observed growth inhibitory activity was sometimes high, suggesting that the relevant sequences may be abundantly represented in the mammalian genome. We speculate that these findings may provide new insights into the molecular mechanisms involved in cellular quiescence and in vitro senescence.

Synthesis of new oxathiazinane dioxides and their in vitro cancer cell growth inhibitory activity

2010 ◽  
Vol 20 (17) ◽  
pp. 5353-5356 ◽  
Author(s):  
Françoise Borcard ◽  
Matthias Baud ◽  
Claudia Bello ◽  
Giovanna Dal Bello ◽  
Francesco Grossi ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cancer Cell ◽  
Inhibitory Activity ◽  
Cancer Cell Growth ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity

Synthesis of New β-Lactam Analogs and Evaluation of Their Histone Deacetylase (HDAC) Activity

2007 ◽  
Vol 62 (11) ◽  
pp. 1459-1464 ◽  
Author(s):  
Seikwan Oh ◽  
Jae-Chul Jung ◽  
Mitchell A. Avery
Keyword(s):  
Histone Deacetylase ◽  
Hdac Inhibitors ◽  
Human Tumor ◽  
Coupling Reactions ◽  
Human Tumor Cell Lines ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Potent Growth ◽  
High Yields

A simple synthesis of the β -lactams 11 - 13 and 16 - 17 as novel histone deacetylase (HDAC) inhibitors is described. The key synthetic strategies involved the O-alkylation of 6-APA and the coupling reactions of freshly prepared N-carbobenzyloxy-L-prolines 5 and 6 and 6-aminopenicillanates 8 - 10 and 15 in high yields. It was found that all compounds show potent growth inhibitory activity on human tumor cell lines, the most potent compound 16 exhibiting an IC50 = 2.1 μM in vitro.

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