The other side to the use of active targeting ligands; the case of folic acid in the targeting of breast cancer

2021 ◽  
pp. 112289
Author(s):  
Lama A. Helmy ◽  
Mohammed Abdel-Halim ◽  
Raghda Hassan ◽  
Aya Sebak ◽  
Haithem A.M. Farghali ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Folic Acid ◽  
The Other ◽  
Active Targeting

scholarly journals Novel TNBC-Targeted DOX-Arsonoliposomes

Proceedings ◽  
2020 ◽  
Vol 78 (1) ◽  
pp. 17
Author(s):  
Maria Mantzari ◽  
Foteini Gartziou ◽  
Eleni Lambrou ◽  
Spyridon Mourtas ◽  
Paraskevi Zagana ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Folic Acid ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Entrapment Efficiency ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Selective Toxicity ◽  
First Results

Arsonoliposomes (ARSL) constitute a particular class of liposomes that incorporate arsonolipids (ARS) into their membranes. ARSL realize selective toxicity to cancer cells; thus, they are an important tool in the treatment of cancer. Folic acid (FA) is widely used in targeted drug delivery due to its high affinity for the folate receptors that are overexpressed in cancer cell membranes. The aim of our studies was to develop novel triple-negative breast cancer (TNBC)-targeted ARSL by incorporating folic acid-conjugated polyethylene-glycol PEG-lipid (FA-PEG-lipid) into their membrane and loading them with anticancer drug doxorubicin (DOX). ARSL incorporating 0.1 mol% of FA-PEG-lipid were prepared and loaded with DOX, using the active loading protocol. They were characterized for their size distribution, zeta potential and drug entrapment efficiency (%). Their cytotoxic activity towards TNBC cell lines, particularly MDA-MB-231 (epithelial human breast cancer cells) and MCF7 (human breast cancer cells), was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT-assay. The first results demonstrated enhanced toxicity of this novel type of ARSL towards cancer cells, which is particularly interesting and deserves further exploitation.

scholarly journals Adhesion of Triple-Negative Breast Cancer Cells under Fluorescent and Soft X-ray Contact Microscopy

2021 ◽  
Vol 22 (14) ◽  
pp. 7279
Author(s):  
Paulina Natalia Osuchowska ◽  
Przemysław Wachulak ◽  
Wiktoria Kasprzycka ◽  
Agata Nowak-Stępniowska ◽  
Maciej Wakuła ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cell Imaging ◽  
Triple Negative ◽  
The Other ◽  
Promising Technique ◽  
X Ray ◽  
Microscopy Technique ◽  
Cancer Cell Adhesion

Understanding cancer cell adhesion could help to diminish tumor progression and metastasis. Adhesion mechanisms are currently the main therapeutic target of TNBC-resistant cells. This work shows the distribution and size of adhesive complexes determined with a common fluorescence microscopy technique and soft X-ray contact microscopy (SXCM). The results presented here demonstrate the potential of applying SXCM for imaging cell protrusions with high resolution when the cells are still alive in a physiological buffer. The possibility to observe the internal components of cells at a pristine and hydrated state with nanometer resolution distinguishes SXCM from the other more commonly used techniques for cell imaging. Thus, SXCM can be a promising technique for investigating the adhesion and organization of the actin cytoskeleton in cancer cells.

scholarly journals Differential Mechanisms of Cell Death Induced by HDAC Inhibitor SAHA and MDM2 Inhibitor RG7388 in MCF-7 Cells

Cells ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 8 ◽  
Author(s):  
Umamaheswari Natarajan ◽  
Thiagarajan Venkatesan ◽  
Vijayaraghavan Radhakrishnan ◽  
Shila Samuel ◽  
Appu Rathinavelu
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Death ◽  
Cancer Cells ◽  
Hdac Inhibitor ◽  
The Other ◽  
Combination Treatments ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
Mcf 7

Gene expression is often altered by epigenetic modifications that can significantly influence the growth ability and progression of cancers. SAHA (Suberoylanilide hydroxamic acid, also known as Vorinostat), a well-known Histone deacetylase (HDAC) inhibitor, can stop cancer growth and metastatic processes through epigenetic alterations. On the other hand, Letrozole is an aromatase inhibitor that can elicit strong anti-cancer effects on breast cancer through direct and indirect mechanisms. A newly developed inhibitor, RG7388 specific for an oncogene-derived protein called MDM2, is in clinical trials for the treatment of various cancers. In this paper, we performed assays to measure the effects of cell cycle arrest resulting from individual drug treatments or combination treatments with SAHA + letrozole and SAHA + RG7388, using the MCF-7 breast cancer cells. When SAHA was used individually, or in combination treatments with RG7388, a significant increase in the cytotoxic effect was obtained. Induction of cell cycle arrest by SAHA in cancer cells was evidenced by elevated p21 protein levels. In addition, SAHA treatment in MCF-7 cells showed significant up-regulation in phospho-RIP3 and MLKL levels. Our results confirmed that cell death caused by SAHA treatment was primarily through the induction of necroptosis. On the other hand, the RG7388 treatment was able to induce apoptosis by elevating BAX levels. It appears that, during combination treatments, with SAHA and RG7388, two parallel pathways might be induced simultaneously, that could lead to increased cancer cell death. SAHA appears to induce cell necroptosis in a p21-dependent manner, and RG7388 seems to induce apoptosis in a p21-independent manner, outlining differential mechanisms of cell death induction. However, further studies are needed to fully understand the intracellular mechanisms that are triggered by these two anti-cancer agents.

scholarly journals Integrative statistical analyses of multiple liquid biopsy analytes in metastatic breast cancer

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Corinna Keup ◽  
Vinay Suryaprakash ◽  
Siegfried Hauch ◽  
Markus Storbeck ◽  
Peter Hahn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Mutual Information ◽  
Hierarchical Clustering ◽  
Liquid Biopsy ◽  
Metastatic Breast ◽  
The Other ◽  
Theoretic Analysis ◽  
Graph Theoretic

Abstract Background Single liquid biopsy analytes (LBAs) have been utilized for therapy selection in metastatic breast cancer (MBC). We performed integrative statistical analyses to examine the clinical relevance of using multiple LBAs: matched circulating tumor cell (CTC) mRNA, CTC genomic DNA (gDNA), extracellular vesicle (EV) mRNA, and cell-free DNA (cfDNA). Methods Blood was drawn from 26 hormone receptor-positive, HER2-negative MBC patients. CTC mRNA and EV mRNA were analyzed using a multi-marker qPCR. Plasma from CTC-depleted blood was utilized for cfDNA isolation. gDNA from CTCs was isolated from mRNA-depleted CTC lysates. CTC gDNA and cfDNA were analyzed by targeted sequencing. Hierarchical clustering was performed within each analyte, and its results were combined into a score termed Evaluation of multiple Liquid biopsy analytes In Metastatic breast cancer patients All from one blood sample (ELIMA.score), which calculates the contribution of each analyte to the overall survival prediction. Singular value decomposition (SVD), mutual information calculation, k-means clustering, and graph-theoretic analysis were conducted to elucidate the dependence between individual analytes. Results A combination of two/three/four LBAs increased the prevalence of patients with actionable signals. Aggregating the results of hierarchical clustering of individual LBAs into the ELIMA.score resulted in a highly significant correlation with overall survival, thereby bolstering evidence for the additive value of using multiple LBAs. Computation of mutual information indicated that none of the LBAs is independent of the others, but the ability of a single LBA to describe the others is rather limited—only CTC gDNA could partially describe the other three LBAs. SVD revealed that the strongest singular vectors originate from all four LBAs, but a majority originated from CTC gDNA. After k-means clustering of patients based on parameters of all four LBAs, the graph-theoretic analysis revealed CTC ERBB2 variants only in patients belonging to one particular cluster. Conclusions The additional benefits of using all four LBAs were objectively demonstrated in this pilot study, which also indicated a relative dominance of CTC gDNA over the other LBAs. Consequently, a multi-parametric liquid biopsy approach deconvolutes the genomic and transcriptomic complexity and should be considered in clinical practice.

Folic acid and vitamin B12 status of vervet monkeys used for nutritional research

1993 ◽  
Vol 27 (1) ◽  
pp. 59-64 ◽  
Author(s):  
F. S. Venter ◽  
H. Cloete ◽  
J. V. Seier ◽  
M. J. Faber ◽  
J. E. Fincham
Keyword(s):  
Folic Acid ◽  
Inverse Relationship ◽  
Atherogenic Diet ◽  
The Other ◽  
Vitamin B ◽  
Plasma Vitamin ◽  
Vervet Monkeys ◽  
Adult Males ◽  
Competitive Protein Binding ◽  
Apparently Healthy

Plasma and red blood cell (RBC) folic acid levels, as well as plasma vitamin B12 levels were determined in Vervet monkeys ( Cercopithecus aethiops). All the vervets were apparently healthy and without symptoms or lesions typical of folic acid and/or vitamin B12 deficiencies. Competitive protein binding radioassays were used to determine folate and vitamin B12 values in animals fed 4 different diets. The B12 levels for all the groups ranged between 866 and 5867 pg/ml and showed an inverse relationship with the FA measurements. The lowest mean RBC folic acid content in a group fed an atherogenic diet for 3 years was 12·8 ng/ml. For the other 3 diets, mean RBC folic acid levels were 90·7, 132·3 and 152·8 ng/ml, respectively. A megadose of 25·6 mg of folic acid per day for 99 days was given to 3 adult males. No obvious toxic effects were observed in these animals although mean RBC folic acid levels increased to 1013 ng/ml.

scholarly journals Epidemiology Study for Cancer Incidences among Patients from Baghdad Carrying Different Types of Cancer.

2018 ◽  
Vol 9 (SPL1) ◽  
Author(s):  
Dawood Salim Edan ◽  
HamedH Khamees
Keyword(s):  
Breast Cancer ◽  
Colorectal Cancer ◽  
Bladder Cancer ◽  
Endometrial Cancer ◽  
Cancer Colorectal ◽  
Cancer Epidemiology ◽  
The Other ◽  
Epidemiology Study ◽  
Different Types ◽  
Prevalence Of Cancer

This study was carried out in Al-Yarmook hospital,laboratories department,Baghdad- Iraq; One hundred thirty three Iraqi patients have been recorded during period May 2014 until December 2014.The current study has demonstrated that five different types of the following cancers: Breast cancer,Skin cancer,colorectal cancer,Bladder cancer and endometrial cancer were enrolled in this study. Comparison among each type of cancer was regarded in age, sex and number. The majority results in cancer epidemiology for the present study were fluctuated between the skin and breast cancer,which showed 33.1% and this,represented the prevalence of cancer among all the other types of cancers. In case of other types,the result has showed 16.5 %,13.5% and 3.7 % for endometrial cancer,Bladder cancer and colorectal cancer,respectively.

scholarly journals Effects of Folic Acid Consumption on Newborn Defects and Miscarriage, and Content Uniformity Analysis of Three Different Brands of Folic Acid Tablets Dosage Forms

2019 ◽  
Vol 34 (4) ◽  
pp. 256-264
Author(s):  
Adel B Mohamed ◽  
Azza M Ali ◽  
Samia A Magid
Keyword(s):  
Folic Acid ◽  
Birth Defects ◽  
Folic Acid Supplementation ◽  
Dosage Forms ◽  
The Other ◽  
P Value ◽  
Folic Acid Deficiency ◽  
Content Uniformity ◽  
Acid Consumption ◽  
Taking Action

There is a recent rise in the number of birth defects. This could be related to folic acid deficiency. Folic acid, as an antioxidant, is an important factor in preventing birth defects during embryonic development. This study, via content uniformity measurements and medical history, aimed to investigate the role of folic acid before and during pregnancy and to measure the content uniformity of different brands of folic acid tablets. The statistical study aimed to determine the relationship between folic acid consumption, miscarriage, and anomalies in newborn babies. The study studied a sample of 300 women based on their medical records. There was no significant effect (p-value = 0.143) of folic acid consumption on the frequency of anomalies. On the other hand, there was a high significant relation (p-value = 0.003) between folic acid consumption and miscarriage. The correlation, principally with miscarriage, coincides with previous studies and highlights the importance of folic acid supplementation before and during gestation. Content uniformity measurements were made on three famous folic acid brands (Folic Acid-Nile, Folicum-Julphar and Wockhardt-UK) available at local pharmacies. Measurements on the three folic acid brands were conducted in compliance with the British Pharmacopoeia (BP) (2010) test for content uniformity. Ten tablets from each brand were tested using the UV spectrophotometric method. The results showed that only the first brand name passed the content uniformity test, while the other two brands did not comply with the standards. This result highlights the problem of under-dosing in commercially available folic acid dosage forms, and identifies the need for taking action towards the implementation of quality control on all medical drugs.  

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