scholarly journals Phenotypic Switching of B16F10 Melanoma Cells as a Stress Adaptation Response to Fe3O4/Salicylic Acid Nanoparticle Therapy

2021 ◽  
Vol 14 (10) ◽  
pp. 1007
Author(s):  
Ion Mîndrilă ◽  
Andrei Osman ◽  
Bogdan Mîndrilă ◽  
Maria Cristina Predoi ◽  
Dan Eduard Mihaiescu ◽  
...  
Keyword(s):  
Salicylic Acid ◽  
Therapeutic Strategy ◽  
Aqueous Dispersion ◽  
Melanoma Cells ◽  
Phenotypic Switching ◽  
Treatment Modalities ◽  
B16f10 Melanoma ◽  
Adaptation Response ◽  
The Impact ◽  
Syngeneic Model

Melanoma is a melanocyte-derived skin cancer that has a high heterogeneity due to its phenotypic plasticity, a trait that may explain its ability to survive in the case of physical or molecular aggression and to develop resistance to therapy. Therefore, the therapy modulation of phenotypic switching in combination with other treatment modalities could become a common approach in any future therapeutic strategy. In this paper, we used the syngeneic model of B16F10 melanoma implanted in C57BL/6 mice to evaluate the phenotypic changes in melanoma induced by therapy with iron oxide nanoparticles functionalized with salicylic acid (SaIONs). The results of this study showed that the oral administration of the SaIONs aqueous dispersion was followed by phenotypic switching to highly pigmented cells in B16F10 melanoma through a cytotoxicity-induced cell selection mechanism. The hyperpigmentation of melanoma cells by the intra- or extracellular accumulation of melanic pigment deposits was another consequence of the SaIONs therapy. Additional studies are needed to assess the reversibility of SaIONs-induced phenotypic switching and the impact of tumor hyperpigmentation on B16F10 melanoma's progression and metastasis abilities.

scholarly journals The Switch between Protective and Nonprotective Autophagy; Implications for Autophagy Inhibition as a Therapeutic Strategy in Cancer

Biology ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 12
Author(s):  
David A. Gewirtz
Keyword(s):  
Tumor Cells ◽  
Therapeutic Strategy ◽  
Response To Therapy ◽  
Treatment Modalities ◽  
System Response ◽  
Metabolic Intermediates ◽  
Response To Chemotherapy ◽  
Radiation Induced ◽  
The Impact ◽  
Autophagy Inhibition

Autophagy, a process of cellular self-degradation and cell survival whereby the cell generates energy and metabolic intermediates under conditions of stress (i.e., nutrient deprivation), is also commonly induced in tumor cells in response to chemotherapy and radiation. While chemotherapy-induced autophagy and radiation-induced autophagy are generally considered to have cytoprotective functions, thereby reducing tumor cell sensitivity (and potentially conferring resistance) to various treatment modalities, autophagy can also be nonprotective; furthermore, the nature of the autophagy can be altered via the “autophagic switch” depending on such factors as the p53 status of the tumor cells. Defective or compromised autophagy has also been associated with neurodegenerative diseases, raising concerns as to the impact of autophagy inhibition on normal tissue function. Furthermore, the impact of autophagy inhibition on the immune system response to therapy as well as the influence of autophagy inhibition in combination with chemotherapy or radiation on critical tissue sites such as the bone marrow remain uncertain. These are factors requiring serious consideration within the context of current clinical efforts to exploit autophagy inhibition as a therapeutic strategy in cancer.

scholarly journals Iron Oxide/Salicylic Acid Nanoparticles as Potential Therapy for B16F10 Melanoma Transplanted on the Chick Chorioallantoic Membrane

Processes ◽  
2020 ◽  
Vol 8 (6) ◽  
pp. 706
Author(s):  
Maria Cristina Predoi ◽  
Ion Mîndrilă ◽  
Sandra Alice Buteică ◽  
Ștefana Oana Purcaru ◽  
Dan Eduard Mihaiescu ◽  
...  
Keyword(s):  
Salicylic Acid ◽  
Iron Oxide ◽  
Local Development ◽  
Survival Rates ◽  
Chorioallantoic Membrane ◽  
Melanoma Cells ◽  
Cytotoxic Action ◽  
B16f10 Melanoma ◽  
Chick Chorioallantoic Membrane ◽  
Induced Apoptosis

Unfavorable prognoses and low survival rates are specific features of metastatic melanoma that justify the concern for the development of new therapeutic strategies. Lately, nanotechnology has become an attractive field of study due to recent advances in nanomedicine. Using a chick chorioallantoic membrane (CAM) implanted with xenografts harvested from C57BL/6 mice with B16F10 melanoma cells, we studied the effects of iron oxide nanoparticles functionalized with salicylic acid (SaMNPs) as a form of therapy on the local development of xenotransplants and CAM vessels. The SaMNPs induced an anti-angiogenic effect on the CAM vessels, which accumulated preferentially in the melanoma cells and induced apoptosis and extensive xenograft necrosis. As a result, this slowed the increase in the xenograft volume and reduced the melanoma cells’ ability to metastasize locally and distally. Further, we demonstrate the use of the chick CAM model as a tool for testing the action of newly synthesized nanocomposites on melanoma xenotransplants. The SaMNPs had a therapeutic effect on B16F10 melanoma due to the synergistic action of the two components of its structure: the coating of the salicylic acid with antiangiogenic and chemotherapeutic action and the core of iron oxides with cytotoxic action.

Inhibitory Effects of Myelophycus simplex Papenfuss Methanol Extract on Melanogenesis in B16F10 Melanoma Cells

2017 ◽  
Vol 46 (1) ◽  
pp. 34-38
Author(s):  
Hyang Suk Kim ◽  
Ji Min Cheon ◽  
Da Hye Kwon ◽  
Eun Ok Choi ◽  
Min Ju Kim ◽  
...  
Keyword(s):  
Methanol Extract ◽  
Melanoma Cells ◽  
Inhibitory Effects ◽  
B16f10 Melanoma ◽  
B16f10 Melanoma Cells

MicroRNA-520c-3p Modulates Doxorubicin-Chemosensitivity in HepG2 Cells

2020 ◽  
Vol 21 (2) ◽  
pp. 237-245 ◽  
Author(s):  
Mohamed A. Ragheb ◽  
Marwa H. Soliman ◽  
Emad M. Elzayat ◽  
Mervat S. Mohamed ◽  
Nada El-Ekiaby ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
Therapeutic Strategy ◽  
Suppressive Effect ◽  
Expression Level ◽  
Tumor Suppressor Function ◽  
Protein Expression Level ◽  
Blot Technique ◽  
Induction Of Apoptosis ◽  
The Impact

Background: Doxorubicin (DOX) is the most common drugs used in cancer therapy, including Hepatocellular Carcinoma (HCC). Drug resistance, is one of chemotherapy’s significant problems. Emerging studies have shown that microRNAs (miRNAs) could participate in regulating this mechanism. Nevertheless, the impact of miRNAs on HCC chemoresistance is still enigmatic. Objective: Investigating the role of miR-520c-3p in enhancement of anti-tumor effect of DOX against HepG2 cells. Methods: Expression profile for liver related miRNAs (384 miRNAs) has been analyzed on HepG2 cells treated with DOX using qRT-PCR. miR-520c-3p, the most deregulated miRNA, was selected for combination treatment with DOX. Expression level for LEF1, CDK2, CDH1, VIM, Mcl-1 and TP53 was evaluated in miR-520c-3p transfected cells. Cell viability, colony formation, wound healing as well as apoptosis assays have been demonstrated. Furthermore, Mcl-1 protein level was measured using western blot technique. Results: The present data indicated that miR-520c-3p overexpression could render HepG2 cells chemo-sensitive to DOX through enhancing its suppressive effects on proliferation, migration, and induction of apoptosis. The suppressive effect of miR-520c-3p involved altering the expression levels of some key regulators of cell cycle, proliferation, migration and apoptosis including LEF1, CDK2, CDH1, VIM, Mcl-1 and TP53. Interestingly, Mcl-1 was found to be one of the potential targets of miR-520c-3p, and its protein expression level was down-regulated upon miR-520c-3p overexpression. Conclusion: Our data referred to the tumor suppressor function of miR-520c-3p that could modulate chemosensitivity of HepG2 cells toward DOX treatment, providing a promising therapeutic strategy in HCC.

scholarly journals Genetic variations influence brain changes in patients with attention-deficit hyperactivity disorder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Santosh K. Yadav ◽  
Ajaz A. Bhat ◽  
Sheema Hashem ◽  
Sabah Nisar ◽  
Madeeha Kamal ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Brain Imaging ◽  
Attention Deficit ◽  
Genetic Variations ◽  
Imaging Genetics ◽  
Treatment Modalities ◽  
Genetic Studies ◽  
Hyperactivity Disorder ◽  
Clinical Biomarkers ◽  
The Impact

AbstractAttention-deficit hyperactivity disorder (ADHD) is a neurological and neurodevelopmental childhood-onset disorder characterized by a persistent pattern of inattentiveness, impulsiveness, restlessness, and hyperactivity. These symptoms may continue in 55–66% of cases from childhood into adulthood. Even though the precise etiology of ADHD is not fully understood, it is considered as a multifactorial and heterogeneous disorder with several contributing factors such as heritability, auxiliary to neurodevelopmental issues, severe brain injuries, neuroinflammation, consanguineous marriages, premature birth, and exposure to environmental toxins. Neuroimaging and neurodevelopmental assessments may help to explore the possible role of genetic variations on ADHD neuropsychobiology. Multiple genetic studies have observed a strong genetic association with various aspects of neuropsychobiological functions, including neural abnormalities and delayed neurodevelopment in ADHD. The advancement in neuroimaging and molecular genomics offers the opportunity to analyze the impact of genetic variations alongside its dysregulated pathways on structural and functional derived brain imaging phenotypes in various neurological and psychiatric disorders, including ADHD. Recently, neuroimaging genomic studies observed a significant association of brain imaging phenotypes with genetic susceptibility in ADHD. Integrating the neuroimaging-derived phenotypes with genomics deciphers various neurobiological pathways that can be leveraged for the development of novel clinical biomarkers, new treatment modalities as well as therapeutic interventions for ADHD patients. In this review, we discuss the neurobiology of ADHD with particular emphasis on structural and functional changes in the ADHD brain and their interactions with complex genomic variations utilizing imaging genetics methodologies. We also highlight the genetic variants supposedly allied with the development of ADHD and how these, in turn, may affect the brain circuit function and related behaviors. In addition to reviewing imaging genetic studies, we also examine the need for complementary approaches at various levels of biological complexity and emphasize the importance of combining and integrating results to explore biological pathways involved in ADHD disorder. These approaches include animal models, computational biology, bioinformatics analyses, and multimodal imaging genetics studies.

scholarly journals Combining tissue and circulating tumor DNA increases the detection rate of a CTNNB1 mutation in hepatocellular carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Stine Karlsen Oversoe ◽  
Michelle Simone Clement ◽  
Britta Weber ◽  
Henning Grønbæk ◽  
Stephen Jacques Hamilton-Dutoit ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mutation Rate ◽  
Detection Rate ◽  
Tumor Tissue ◽  
Circulating Tumor Dna ◽  
Treatment Modalities ◽  
Advanced Hepatocellular Carcinoma ◽  
Tissue Samples ◽  
The Impact ◽  
Tumor Dna

Abstract Background and aims Studies suggest that mutations in the CTNNB1 gene are predictive of response to immunotherapy, an emerging therapy for advanced hepatocellular carcinoma (HCC). Analysis of circulating tumor DNA (ctDNA) offers the possibility of serial non-invasive mutational profiling of tumors. Combining tumor tissue and ctDNA analysis may increase the detection rate of mutations. This study aimed to evaluate the frequency of the CTNNB1 p.T41A mutation in ctDNA and tumor samples from HCC patients and to evaluate the concordance rates between plasma and tissue. We further evaluated changes in ctDNA after various HCC treatment modalities and the impact of the CTNNB1 p.T41A mutation on the clinical course of HCC. Methods We used droplet digital PCR to analyze plasma from 95 patients and the corresponding tumor samples from 37 patients during 3 years follow up. Results In tumor tissue samples, the mutation rate was 8.1% (3/37). In ctDNA from HCC patients, the CTNNB1 mutation rate was 9.5% (9/95) in the pre-treatment samples. Adding results from plasma analysis to the subgroup of patients with available tissue samples, the mutation detection rate increased to 13.5% (5/37). There was no difference in overall survival according to CTNNB1 mutational status. Serial testing of ctDNA suggested a possible clonal evolution of HCC or arising multicentric tumors with separate genetic profiles in individual patients. Conclusion Combining analysis of ctDNA and tumor tissue increased the detection rate of CTNNB1 mutation in HCC patients. A liquid biopsy approach may be useful in a tailored therapy of HCC.

scholarly journals Physiological Responses of Salinized Fenugreek (Trigonellafoenum-graecum L.) Plants to Foliar Application of Salicylic Acid

Plants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 657
Author(s):  
Reda E. Abdelhameed ◽  
Arafat Abdel Hamed Abdel Latef ◽  
Rania S. Shehata
Keyword(s):  
Salicylic Acid ◽  
Salt Stress ◽  
Foliar Application ◽  
Shikimic Acid ◽  
Plant Tolerance ◽  
Physiological Mechanisms ◽  
Content Index ◽  
Malondialdehyde Content ◽  
Total Free Amino Acids ◽  
The Impact

Considering the detrimental effects of salt stress on the physiological mechanisms of plants in terms of growth, development and productivity, intensive efforts are underway to improve plant tolerance to salinity. Hence, an experiment was conducted to assess the impact of the foliar application of salicylic acid (SA; 0.5 mM) on the physiological traits of fenugreek (Trigonellafoenum-graecum L.) plants grown under three salt concentrations (0, 75, and 150 mM NaCl). An increase in salt concentration generated a decrease in the chlorophyll content index (CCI); however, the foliar application of SA boosted the CCI. The malondialdehyde content increased in salt-stressed fenugreek plants, while a reduction in content was observed with SA. Likewise, SA application induced an accumulation of proline, total phenolics, and flavonoids. Moreover, further increases in total free amino acids and shikimic acid were observed with the foliar application of SA, in either control or salt-treated plants. Similar results were obtained for ascorbate peroxidase, peroxidase, polyphenol oxidase, and catalase with SA application. Hence, we concluded that the foliar application of SA ameliorates salinity, and it is a growth regulator that improves the tolerance of fenugreek plants under salt stress.

scholarly journals Improving the Biocontrol Potential of Bacterial Antagonists with Salicylic Acid against Brown Rot Disease and Impact on Nectarine Fruits Quality

Agronomy ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 209
Author(s):  
Nadia Lyousfi ◽  
Rachid Lahlali ◽  
Chaimaa Letrib ◽  
Zineb Belabess ◽  
Rachida Ouaabou ◽  
...  
Keyword(s):  
Salicylic Acid ◽  
Disease Severity ◽  
Mycelial Growth ◽  
Brown Rot ◽  
Antagonistic Bacteria ◽  
Biological Treatments ◽  
Rot Disease ◽  
The Impact

The main objective of this study was to evaluate the ability of both antagonistic bacteria Bacillus amyloliquefaciens (SF14) and Alcaligenes faecalis (ACBC1) used in combination with salicylic acid (SA) to effectively control brown rot disease caused by Monilinia fructigena. Four concentrations of salicylic acid (0.5%, 2%, 3.5%, and 5%) were tested under in vitro and in vivo conditions. Furthermore, the impact of biological treatments on nectarine fruit parameters’ quality, in particular, weight loss, titratable acidity, and soluble solids content, was evaluated. Regardless of the bacterium, the results indicated that all combined treatments displayed a strong inhibitory effect on the mycelial growth of M. fructigena and disease severity. Interestingly, all SA concentrations significantly improved the biocontrol activity of each antagonist. The mycelial growth inhibition rate ranged from 9.79% to 88.02% with the highest reduction rate recorded for bacterial antagonists in combination with SA at both concentrations of 0.5% and 3.5%. The in vivo results confirmed the in vitro results with a disease severity varying from 0.00% to 51.91%. A significant biocontrol improvement was obtained with both antagonistic bacteria when used in combination with SA at concentrations of 0.5% and 2%. The lowest disease severity observed with ACBC1 compared with SF14 is likely due to a rapid adaptation and increase of antagonistic bacteria population in wounded sites. The impact of all biological treatments revealed moderate significant changes in the fruit quality parameters with weight loss for several treatments. These results suggest that the improved disease control of both antagonistic bacteria was more likely directly linked to both the inhibitory effects of SA on pathogen growth and induced fruit resistance.

scholarly journals Amikacin or Vancomycin Exposure Alters the Postnatal Serum Creatinine Dynamics in Extreme Low Birth Weight Neonates

2021 ◽  
Vol 18 (2) ◽  
pp. 662
Author(s):  
Tamara van Donge ◽  
Anne Smits ◽  
John van den Anker ◽  
Karel Allegaert
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Serum Creatinine ◽  
Potential Effect ◽  
Extremely Low Birth Weight ◽  
Treatment Modalities ◽  
Antibiotic Exposure ◽  
Sensitive Tool ◽  
Elbw Neonates ◽  
The Impact

Background: Disentangling renal adverse drug reactions from confounders remains a major challenge to assess causality and severity in neonates, with additional limitations related to the available tools (modified Kidney Disease Improving Global Outcome, or Division of Microbiology and Infectious Diseases pediatric toxicity table). Vancomycin and amikacin are nephrotoxic while still often prescribed in neonates. We selected these compounds to assess their impact on creatinine dynamics as a sensitive tool to detect a renal impairment signal. Methods: A recently developed dynamical model that characterized serum creatinine concentrations of 217 extremely low birth weight (<1000 g, ELBW) neonates (4036 observations) was enhanced with data on vancomycin and/or amikacin exposure to identify a potential effect of antibiotic exposure by nonlinear mixed-effects modelling. Results: Seventy-seven percent of ELBW patients were exposed to either vancomycin or amikacin. Antibiotic exposure resulted in a modest increase in serum creatinine and a transient decrease in creatinine clearance. The serum creatinine increase was dependent on gestational age, illustrated by a decrease with 56% in difference in serum creatinine between a 24 or 32-week old neonate, when exposed in the 3rd week after birth. Conclusions: A previously described model was used to explore and quantify the impact of amikacin or vancomycin exposure on creatinine dynamics. Such tools serve to explore minor changes, or compare minor differences between treatment modalities.

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