scholarly journals Novel Biocompatible and Biodegradable PCL-PLA/ Iron Oxide NPs Marker Clip Composite for Breast Cancer Biopsy

Polymers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1307 ◽  
Author(s):  
Angel Hernandez-Martinez ◽  
Gustavo Molina ◽  
Rodrigo Esparza ◽  
Ángel Luis Rodríguez ◽  
Martha Cruz-Soto ◽  
...  

Strength and biocompatibility of composite materials (using a polymer matrix) are used in medicine for various devices such as prostheses and marker clips (biomarkers). Marker clips indicate the site of a lesion in the body, specifically for breast cancer diagnosis or treatment. In general, marker clips are made of steel or titanium, but lately, materials containing biodegradable polymers had been proposed. Our hypothesis is that a copolymer of polylactic acid and poly(ε-caprolactone) (PLA-PCL) could be used as marker clip material. After evaluating different polymer rates performance, metallic nanoparticles (NPs) were included to enhance the stability of the best copolymer and a marker clip prototype was proposed. Characterization of nanoparticles was made by dynamic light scattering (DLS), X-ray diffraction (XRD) and magnetic measurements. Mechanical, thermal and radiopacity properties were evaluated for composites formulation. In vitro, radiopaque experiments showed that BM-2 composite had the best performance. In vivo experiments showed that, after five months, the marker clip prototype maintained its shape, visibility and contrast properties. In consequence, a novel formulation of composite (PLA-PCL/metallic nanoparticles) is suitable for further studies as an alternative material for marker clips for breast cancer lesions.

Author(s):  
O.E. Luneva ◽  

Food additives are positioned as harmless, although, their components affectthe physiological processes associated with the permeability of the wall of the gastrointestinal tract (GIT) and intestinal microbiota. This article describes thecarrageenan supplement and its effects on the body in in vitro and in vivo experiments. The experimental part is devoted to analysis of the intestinalmicrobiota of laboratory rats with the consumption of the carrageenan dietary supplement in the amount of about 4,4 % of the standard feed.


2021 ◽  
Vol 23 (1) ◽  
pp. 129
Author(s):  
Huinan Qu ◽  
Da Qi ◽  
Xinqi Wang ◽  
Yuan Dong ◽  
Qiu Jin ◽  
...  

Claudin 6 (CLDN6) was found to be a breast cancer suppressor gene, which is lowly expressed in breast cancer and inhibits breast cancer cell proliferation upon overexpression. However, the mechanism by which CLDN6 inhibits breast cancer proliferation is unclear. Here, we investigated this issue and elucidated the molecular mechanisms by which CLDN6 inhibits breast cancer proliferation. First, we verified that CLDN6 was lowly expressed in breast cancer tissues and that patients with lower CLDN6 expression had a worse prognosis. Next, we confirmed that CLDN6 inhibited breast cancer proliferation through in vitro and in vivo experiments. As for the mechanism, we found that CLDN6 inhibited c–MYC–mediated aerobic glycolysis based on a metabolomic analysis of CLDN6 affecting cellular lactate levels. CLDN6 interacted with a transcriptional co–activator with PDZ-binding motif (TAZ) and reduced the level of TAZ, thereby suppressing c–MYC transcription, which led to a reduction in glucose uptake and lactate production. Considered together, our results suggested that CLDN6 suppressed c–MYC–mediated aerobic glycolysis to inhibit the proliferation of breast cancer by TAZ, which indicated that CLDN6 acted as a novel regulator of aerobic glycolysis and provided a theoretical basis for CLDN6 as a biomarker of progression in breast cancer.


1994 ◽  
Vol 12 (11) ◽  
pp. 2460-2470 ◽  
Author(s):  
P E Goss ◽  
K M Gwyn

PURPOSE AND DESIGN: One way to deprive hormone-dependent breast cancer of estrogen is to prevent its synthesis. This is achievable by inhibiting the aromatase cytochrome P-450 (P-450arom) enzyme complex responsible for the ultimate step in estrogen production. A new generation of specific and selective aromatase inhibitors is currently under investigation. The purpose of this review is to outline the preclinical test systems for screening these inhibitors, to summarize the preclinical and clinical data published to date, and to discuss the future application of these inhibitors in the management of breast cancer. RESULTS AND CONCLUSION: Disadvantages to the use of earlier inhibitors are described. In vitro and in vivo experiments that reflect the potency and selectivity of new inhibitors are highlighted. From preliminary clinical trials, these inhibitors appear to have excellent pharmacokinetic profiles and produce few side effects when administered orally. Activity against postmenopausal metastatic breast cancer has been demonstrated for the agents reviewed. They are all now in phase III testing to determine their relative efficacy in this setting. Their application in combination with both hormone therapy and chemotherapy, in premenopausal metastatic disease, and in the adjuvant setting in both premenopausal and postmenopausal women remains to be defined.


2020 ◽  
Author(s):  
Anna Wójcik-Gładysz

Discovered in 1999, ghrelin, is one of the peptides co-creating the hypothalamicgastrointestinal axis, otherwise known as the brain-gut axis. Ghrelin participates in many physiological processes and spectrum of its activity is still being discovered. This 28 amino acid peptide ‒ a product of the ghrl gene, was found in all vertebrates and is synthesized and secreted mainly from enteroendocrine X/A cells located in the gastric mucosa of the stomach. Expression of the ghrelin receptor has been found in many nuclei of the hypothalamus involved in appetite regulation. Therefore it’s presumed that ghrelin is one of the crucial hormones deciphering the energy status required for the maintenance of organism homeostasis. Ghrelin acts as a signal of starvation or energy insufficiency and its level in plasma is reduced after the meal. Neuropeptide Y (NPY) and agouti-related peptide (AgRP; NPY/AgRP) neurons located in the arcuate nucleus (ARC) area are the main target of ghrelin in the hypothalamus. This subpopulation of neurons is indispensable for inducing orexigenic action of ghrelin. Moreover ghrelin acting as a neurohormone, mainly in the hypothalamus area, plays an important role in the regulation of growth and reproduction processes. Indeed, ghrelin action on reproductive processes has been observed in the systemic effects exerted at both hypothalamus-pituitary and gonadal levels. Similarly the GH-releasing ghrelin action was observed both on the hypothalamus level and directly on the somatotrophic cells in the pituitary and this dose-related GH releasing activity was found in in vitro as well as in in vivo experiments. In recent years, numerous studies revealed that ghrelin potentially takes part in the treatment of diseases associated with serious disturbances in the organism energy balance and/or functioning of the gastrointestinal tract. It was underlined that ghrelin may be a hormone with a broad spectrum of therapeutic effect on obesity and anorexia nervosa, as well as may also have protective effect on neurodegenerative diseases, inflammatory disorders or functional changes in the body caused by cancers. In overall, ghrelin treatment has been tested in over 100 preclinical studies with healthy volunteers as well as patients with various types of cancer, eating disorders such as anorexia nervosa and bulimia nervosa. It was observed that ghrelin has an excellent clinical safety profile and emerging side effects occurred only in 3–10% of patients and did not constitute a sufficient premise to discontinue the therapy. In general, it can be concluded that ghrelin may be sufficiently used as a prescription drug.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yixiang Huang ◽  
Wenfang Zheng ◽  
Changle Ji ◽  
Xuehui Wang ◽  
Yunhe Yu ◽  
...  

AbstractBreast cancer (BC) is one of the most fatal diseases among women all over the world. Non-coding RNAs including circular RNAs (circRNAs) have been reported to be involved in different aspects during tumorigenesis and progression. In this study, we aimed to explore the biological functions and underlying mechanism of circRPPH1 in BC. Candidate circRNAs were screened in dataset GSE101123 from Gene Expression Omnibus (GEO) database and a differentially expressed circRNA, circRPPH1, was discovered in BC. CircRPPH1 expression was higher in the cancerous tissue compared to paired adjacent tissue. Further in vitro and in vivo experiments indicated that circRPPH1 acted as an oncogene in BC. In addition, circRPPH1 was mainly localized in cytoplasm and played the role of miR-512-5p sponge. By sequestering miR-512-5p from the 3′-UTR of STAT1, circRPPH1 inhibited the suppressive role of miR-512-5p, stabilized STAT1 mRNA in BC and finally affected BC progression. In conclusion, these findings indicated that circRPPH1 acted as an oncogene and regulated BC progression via circRPPH1-miR-512-5p-STAT1 axis, which might provide a potential therapeutic target for BC treatment.


2020 ◽  
Author(s):  
Hang Chen ◽  
Sifan Huang ◽  
Heyi Wang ◽  
Xinmei Chen ◽  
Haiyan Zhang ◽  
...  

Abstract Background: Combination of the prodrug technique with an albumin nanodrug-loaded system is a novel promising approach for cancer treatment. However, the long-lasting and far-reaching challenge for the treatment of cancers lies in how to construct the albumin nanometer drug delivery system with lead compounds and their derivatives. Results: In this study, we reported the preparation of injectable albumin nanoparticles (NPs) with a high and quantitative drug loading system based on the NabTM technology of paclitaxel palmitate (PTX-PA). Our experimental study on drug tissue distribution in vivo demonstrated that the paclitaxel palmitate albumin NPs (Nab-PTX-PA) remained in the tumor for a longer time post injection. Compared with saline and Abraxane® (nanoparticle albumin-bound (nab)-paclitaxel), intravenous injection of Nab-PTX-PA not only reduced the toxicity of the drug in normal organs and increased the body weight of the animals but maintained sustained release of paclitaxel (PTX) in the tumor, thereby displaying an excellent antitumor activity. Blood routine analysis showed that Nab-PTX-PA had fewer adverse effects or less toxicity to the normal organsand more importantly it inhibited tumor cell proliferation more effectively as compared with commercial Abraxane®.Conclusions: This carrier strategy for small molecule drugs is based on naturally evolved interactions between LCFAs(Long Chain Fatty Acids) and HSA(human serum albumin), demonstrated here for PTX. Nab-PTX-PA shows higher maximum tolerated doses and increased efficacy in vivo in breast cancer models, as compared to Abraxane for FDA-approved clinical formulations. This novel injectable Nab-PTX-PA platform has great potential as an effective drug delivery system in the treatment of breast cancer.


Author(s):  
Sundar Ram Naganathan ◽  
Marko Popovic ◽  
Andrew C Oates

The body axis of vertebrate embryos is periodically segmented into bilaterally symmetric pairs of somites. The anteroposterior (AP) length of somites, their position and left-right symmetry are thought to be molecularly determined prior to somite morphogenesis. Here we discover that in zebrafish embryos, initial somite AP lengths and positions are imprecise and consequently many somite pairs form left-right asymmetrically. Strikingly, these imprecisions are not left unchecked and we find that AP lengths adjust within an hour after somite formation, thereby increasing morphological symmetry. We find that AP length adjustments result entirely from changes in somite shape without change in somite volume, with changes in AP length being compensated by corresponding changes in mediolateral length. The AP adjustment mechanism is facilitated by somite surface tension, which we show by comparing in vivo experiments and in vitro single-somite explant cultures with a mechanical model. Length adjustment is inhibited by perturbation of Integrin and Fibronectin, consistent with their involvement in surface tension. In contrast, the adjustment mechanism is unaffected by perturbations to the segmentation clock, thus revealing a distinct process that determines morphological segment lengths. We propose that tissue surface tension provides a general mechanism to adjust shapes and ensure precision and symmetry of tissues in developing embryos.


2021 ◽  
Vol 93 (5) ◽  
pp. 635-639
Author(s):  
Andrei V. Gordeev ◽  
Elena A. Galushko ◽  
Natalia M. Savushkina

The significant humoral effect of the renin-angiotensin-aldosterone system on the regulation of the cardiovascular system and blood pressure has long been widely known. However, the identification and interpretation of new components of renin-angiotensin-aldosterone system in recent years can significantly expand the range of its potential effects on the body. The anti-inflammatory effect of drugs that block angiotensin II and its receptors, including in rheumatic diseases, can become practically significant for General therapists by their effect on reducing the concentration of inflammatory mediators and angiogenesis processes. The organoprotective and anti-inflammatory potentials of drugs that reduce the production of at demonstrated in vitro and in vivo experiments allow us to consider them as first-line angiotropic agents in patients with rheumatoid arthritis, especially in the presence of pathology of the cardiovascular system and kidneys.


2019 ◽  
Vol 56 (6) ◽  
pp. 753-759
Author(s):  
N. M. Savushkina ◽  
E. A. Galushko ◽  
N. V. Demidova ◽  
A. V. Gordeev

At present, the role of the renin-angiotensin system (RAS) in regulating the cardiovascular system and maintaining water and electrolyte homeostasis has been well studied. However, over the past decades, new components of the RAS have been identified, suggesting a wider range of its potential effects on the body. It is of fundamentally importance for rheumatologists to affect inflammation, including rheumatoid inflammation, through blockade of angiotensin (AT) II formation via the effects of AT 1–7 and angiotensin-converting enzyme inhibitors, as well as through suppression of angiogenesis, primarily by reducing the production of endothelial growth factor. The organ-protective and antiinflammatory potential of drugs that reduce the production of AT, which has been proven in in vitro and in vivo experiments, allows us to consider them as first-line angiotropic agents in patients with rheumatoid arthritis, especially in the presence of concomitant hypertension and/or nephropathy.


Toxins ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 360 ◽  
Author(s):  
Yosuke Uchiyama ◽  
Masahiko Takino ◽  
Michiko Noguchi ◽  
Nozomi Shiratori ◽  
Naoki Kobayashi ◽  
...  

Citreoviridin (CTVD), a mycotoxin called yellow rice toxin, is reported to be related to acute cardiac beriberi; however, its toxicokinetics remain unclear. The present study elucidated the toxicokinetics through in vivo experiments in swine and predicted the human toxicokinetics by comparing the findings to those from in vitro experiments. In vivo experiments revealed the high bioavailability of CTVD (116.4%) in swine. An intestinal permeability study using Caco-2 cells to estimate the toxicokinetics in humans showed that CTVD has a high permeability coefficient. When CTVD was incubated with hepatic S9 fraction from swine and humans, hydroxylation and methylation, desaturation, and dihydroxylation derivatives were produced as the predominant metabolites. The levels of these products produced using human S9 were higher than those obtained swine S9, while CTVD glucuronide was produced slowly in human S9 in comparison to swine S9. Furthermore, the elimination of CTVD by human S9 was significantly more rapid in comparison to that by swine S9. These results suggest that CTVD is easily absorbed in swine and that it remains in the body where it is slowly metabolized. In contrast, the absorption of CTVD in humans would be the same as that in swine, although its elimination would be faster.


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