<![CDATA[Melanoma]]> https://www.eurekaselect.com RSS Feed for Disease Wise Article | BenthamScience EurekaSelect (+http://eurekaselect.com) Fri, 29 Mar 2024 09:11:27 +0000 <![CDATA[Melanoma]]> https://www.eurekaselect.com https://www.eurekaselect.com <![CDATA[Recent Advances in Herbal Nanomedicines for Cancer Treatment]]>https://www.eurekaselect.comarticle/106886 <![CDATA[Bioactive Compounds Isolated from Defatted Microalgal Biomasses of <i>Botryococcus Braunii</i> and <i>Dunaliella Tertiolecta</i> showing a Tyrosinase Inhibitory Activity]]>https://www.eurekaselect.comarticle/106645Aims: This study aims to elucidate the structural difference and biochemical properties of bioactive compounds of microalgal biomasses.

Background: The structural difference and biochemical properties of bioactive compounds termed as Water-Soluble Macromolecules (WSMs) are interested in evaluating their biological activities.

Methods: This study was performed to elucidate the structural difference and biochemical properties of bioactive compounds termed as Water-Soluble Macromolecules (WSMs) isolated from defatted microalgal biomasses of Botryococcus braunii and Dunaliella tertiolecta.

Results: The compositional analysis of both WSMs revealed that WSM-Bb is a hetero-macromolecule consisting of various monosaccharides, whereas WSM-Dt was characterized as a homo-- macromolecule that mainly consists of glucose. Interestingly, WSM-Bb showed the significant tyrosinase inhibitory activity with the increase of both the concentration and reaction time. Whereas there was no significant inhibitory activity observed by WSM-Dt.

Conclusion: Inhibitory action of WSM-Bb toward both tyrosinase and tyrosine in either simultaneous or separate reaction may be mainly due to the physical affinity of WSM-Bb. These results emphasize the identification of the primary components of these WSMs and their relevance with the antioxidant function.

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<![CDATA[Identification of Key mRNAs, miRNAs, and mRNA-miRNA Network Involved in Papillary Thyroid Carcinoma]]>https://www.eurekaselect.comarticle/107184 Methods: In this study, multiple bioinformatics methods were employed, including differential expression analysis, gene set enrichment analysis, and miRNA-mRNA interaction network construction.

Results: Firstly, we investigated the key miRNAs that regulated significantly more differentially expressed genes based on GSEA method. Secondly, we searched for the key miRNAs based on the mRNA-miRNA interaction subnetwork involved in PTC. We identified hsa-mir-1275, hsa-mir-1291, hsa-mir-206 and hsa-mir-375 as the key miRNAs involved in PTC pathogenesis.

Conclusion: The integrated analysis of the gene and miRNA expression data not only identified key mRNAs, miRNAs, and mRNA-miRNA network involved in papillary thyroid carcinoma, but also improved our understanding of the pathogenesis of PTC.]]>
<![CDATA[Comprehensive Analysis Reveals GPRIN1 is a Potential Biomarker for Non-sm all Cell Lung Cancer]]>https://www.eurekaselect.comarticle/106983Background: Non-small cell lung cancer (NSCLC) is one of the most leading cause of tumor related mortality worldwide. However, the prognosis of NSCLC remained to be poor and the mechanisms remained to be further investigated.

Objective: This study aimed to evaluate whether GPRIN1 could be a potential biomarker for NSCLC.

Methods: The Cancer Genome Atlas (TCGA, https://cancergenome.nih.gov/) and GEO database(http://www.ncbi.nlm.nih.gov/geo) were used to analyze the GPRIN1 expression between normal and human cancers. The protein-protein interaction among centromere proteins was determined using STRING database (http://www.bork.emblheidelberg.de/STRING/). GraphPad Prism 5.0 software was utilized for the independent and paired samples’ t-test or ANOVA to analyze the difference of GPRIN1 expression between two groups.

Results: This study showed GPRIN1 was overexpressed and correlated to shorter OS time in human cancers. In NSCLC, we found that GPRIN1 was up-regulated in NSCLC samples compared to normal lung tissues by analyzing TCGA and GEO datasets. Bioinformatics analysis indicated that this gene was involved in regulating cancer proliferation and metabolism. Finally, we identified key targets of GPRIN1 in NSCLC by constructing PPl networks, including MCM3, KIF20A, UHRF1, BRCA1, KIF4A, HMMR, KIF18B, KIFC1, ASPM, and NCAPG2.

Conclusion: These analyses showed GPRIN1 could act as a prognosis biomarker in patients with NSCLC.

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<![CDATA[Dual-target Inhibitors Based on BRD4: Novel Therapeutic Approaches for Cancer]]>https://www.eurekaselect.comarticle/107247Background: Currently, cancer continues being a dramatically increasing and serious threat to public health. Although many anti-tumor agents have been developed in recent years, the survival rate of patients is not satisfactory. The poor prognosis of cancer patients is closely related to the occurrence of drug resistance. Therefore, it is urgent to develop new strategies for cancer treatment. Multi-target therapies aim to have additive or synergistic effects and reduce the potential for the development of resistance by integrating different pharmacophores into a single drug molecule. Given the fact that majority of diseases are multifactorial in nature, multi-target therapies are being exploited with increasing intensity, which has brought improved outcomes in disease models and obtained several compounds that have entered clinical trials. Thus, it is potential to utilize this strategy for the treatment of BRD4 related cancers. This review focuses on the recent research advances of dual-target inhibitors based on BRD4 in the aspect of anti-tumor.

Methods: We have searched the recent literatures about BRD4 inhibitors from the online resources and databases, such as pubmed, elsevier and google scholar.

Results: In the recent years, many efforts have been taken to develop dual-target inhibitors based on BRD4 as anti-cancer agents, such as HDAC/BRD4 dual inhibitors, PLK1/BRD4 dual inhibitors and PI3K/BRD4 dual inhibitors and so on. Most compounds display good anti-tumor activities.

Conclusion: Developing new anti-cancer agents with new scaffolds and high efficiency is a big challenge for researchers. Dual-target inhibitors based on BRD4 are a class of important bioactive compounds. Making structural modifications on the active dual-target inhibitors according to the corresponding structure-activity relationships is of benefit to obtain more potent anti-cancer leads or clinical drugs. This review will be useful for further development of new dual-target inhibitors based on BRD4 as anti-cancer agents.

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<![CDATA[The Therapeutic Applications of Exosomes in Different Types of Diseases: A Review]]>https://www.eurekaselect.comarticle/107241 <![CDATA[Recent Progress in the Development of Quinoline Derivatives for the Exploitation of Anti-Cancer Agents]]>https://www.eurekaselect.comarticle/106665Background: Along with the progress in medicine and therapies, the exploitation of anti-cancer agents focused more on the vital signaling pathways and key biological macromolecules. With rational design and advanced synthesis, quinoline derivatives have been utilized frequently in medicinal chemistry, especially in developing anti-cancer drugs or candidates.

Methods: Using DOI searching, articles published before 2020 all over the world have been reviewed as comprehensively as possible.

Results: In this review, we selected the representative quinoline derivate drugs in market or clinical trials, classified them into five major categories with detailed targets according to their main mechanisms, discussed the relationship within the same mechanism, and generated a summative discussion with prospective expectations. For each mechanism, the introduction of the target was presented, with the typical examples of quinoline derivate drugs.

Conclusion: This review has highlighted the quinoline drugs or candidates, suited them into corresponding targets in their pathways, summarized and discussed. We hope that this review may help the researchers who are interested in discovering quinoline derivate anti-cancer agents obtain considerable understanding of this specific topic. Through the flourishing period and the vigorous strategies in clinical trials, quinoline drugs would be potential but facing new challenges in the future.

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<![CDATA[Circular RNAs and Glioma: Small Molecule with Big Actions]]>https://www.eurekaselect.comarticle/107243 <![CDATA[Heat Shock Proteins Regulating Toll-like Receptors and the Immune System could be a Novel Therapeutic Target for Melanoma]]>https://www.eurekaselect.comarticle/106524 <![CDATA[Resveratrol: A New Potential Therapeutic Agent for Melanoma?]]>https://www.eurekaselect.comarticle/102945Melanoma is the most life-threatening and aggressive class of skin malignancies. The incidence of melanoma has steadily increased. Metastatic melanoma is greatly resistant to standard antimelanoma treatments such as chemotherapy, and the 5-year survival rate of cases with melanoma who have a metastatic form of the disease is less than 10%. The contributing role of apoptosis, angiogenesis and autophagy in the pathophysiology of melanoma has been previously demonstrated. Thus, it is extremely urgent to search for complementary therapeutic approaches that could enhance the quality of life of subjects and reduce treatment resistance and adverse effects. Resveratrol, known as a polyphenol component present in grapes and some plants, has anti-cancer properties due to its function as an apoptosis inducer in tumor cells, and anti-angiogenic agent to prevent metastasis. However, more clinical trials should be conducted to prove resveratrol efficacy.

Herein, for the first time, we summarize the current knowledge of anti-cancerous activities of resveratrol in melanoma.

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<![CDATA[Multifunctional Hydroxyapatite-based Nanoparticles for Biomedicine: Recent Progress in Drug Delivery and Local Controlled Release]]>https://www.eurekaselect.comarticle/105899 <![CDATA[Anticancer Properties of Amino Acid and Peptide Derivatives of Mycophenolic Acid]]>https://www.eurekaselect.comarticle/106667Background: Although Mycophenolic Acid (MPA) is applied as prodrugs in clinic as an immunosuppressant, it also possesses anticancer activity. MPA acts as Inosine-5’-Monophosphate Dehydrogenase (IMPDH) inhibitor, where the carboxylic group at the end of the side chain interacts with Ser 276 of the enzyme via hydrogen bonds. Therefore, MPA derivatives with other polar groups indicated high inhibition too. On the other hand, potent anticancer agents like dacarbazine and cisplatin give numerous side-effects.

Objective: Based on the literature data, MPA derivatives should be explored towards anticancer properties. Conversion of the carboxylic group of MPA to amide could maintain antiproliferative activity. Therefore, we decided to investigate several amino acid and peptide derivatives of MPA against chosen cancer cell lines in vitro.

Methods: Amides of MPA hold threonine and arginine amino acid unit. These amino acid derivatives were tested as L and D enantiomers and both in free acid and methyl esters forms. Additionally, MPA was modified with tuftsin or retro-tuftsin as biologically active peptides, which could act as a drug carrier.

Results: Amino acid and peptide derivatives of MPA were investigated in vitro as potential anticancer agents on cell lines: Ab melanoma, A375 melanoma and SHSY5Y neuroblastoma. The activity of the tested compounds was compared to parent MPA and known chemotherapeutics: dacarbazine and cisplatin.

Conclusion: Amino acid moiety and the sequence of amino acids in the peptide part influenced observed activity. The most active amino acid MPA analogues occurred to be D and L-threonine derivatives as methyl esters, probably due to better cell membrane penetration.

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<![CDATA[Paris Saponin VII Induces Apoptosis and Cell Cycle Arrest in Erythroleukemia Cells by a Mitochondrial Membrane Signaling Pathway]]>https://www.eurekaselect.comarticle/107359Background and Purpose: Leukemia is considered a top-listed ailment, according to WHO, which contributes to the death of a major population of the world every year. Paris Saponin VII (PS), a saponin which was isolated from the roots of Trillium kamtschaticum, from our group, was reported to provide hemostatic, cytotoxic and antimicrobial activities. However, its molecular mechanism underlying the anti-proliferative effects remains unclear. Thus, this study hypothesized to assess that mechanism in PS treated HEL cells.

Methods: The MTT assay was used to analyze the PS inhibited cell viability in the HEL cells. We further found that PS could induce S phase cell cycle arrest through flow cytometry as well as the western blot analysis of intrinsic and extrinsic apoptotic molecules.

Results: The MTT assay showed the IC50 concentration of PS as 0.667μM. The study revealed that PS treatment inhibits cell proliferation dose-dependently. It further caused mitochondrial membrane potential changes by PS treatment. Mechanistic protein expression revealed a dose-dependent upsurge for Bid and Bim molecules, while Bcl2 and PARP expression levels were significantly (P<0.05) down-regulated in PS treated HEL cells resulting in caspase -3 release and increased the Bim levels upon 24h of incubation.

Conclusion: These findings indicate that PS possesses an excellent anti-leukemic activity via the regulation of the mitochondrial pathway, leading to S phase cell cycle arrest and caspase-dependent apoptosis, suggesting it as a potential alternative chemotherapeutic agent for leukemia patients.

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<![CDATA[Classifications and Clinical Assessment of Haemorrhoids: The Proctologist’s Corner]]>https://www.eurekaselect.comarticle/105199Background: Haemorrhoidal disease (HD) is a benign condition affecting a considerable part of adult population. HD can be considered a social and economic burden with high impact on patients’ lifestyle. Several new techniques and devices have been proposed for HD treatment; however, preoperative assessment is essential and the use of classification system is recommended.

Methods: In the last two decades many studies described the preoperative assessment and several attempts of classification for HD. This review focuses on the most relevant studies found in literature where classification systems and clinical evaluation with differential diagnosis have been evaluated.

Results: The knowledge of classification systems and differential diagnosis for HD has been shown to play a central role in the clinical assessment and the best treatment choice. Although there are new challenging techniques and devices for HD treatment, a preoperative assessment is always mandatory.

Conclusion: Preoperative clinical evaluation is essential for HD patient treatment and outcome. Classification systems are useful for the therapeutic choice and researches on new medical or surgical treatments. In fact, the international guidelines advise several therapeutic options depending on the severity of the HD.

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<![CDATA[A Systems Biology Approach for miRNA-mRNA Expression Patterns Analysis in Rheumatoid Arthritis]]>https://www.eurekaselect.comarticle/107126Objective: Considering the molecular complexity and heterogeneity of rheumatoid arthritis (RA), the identification of novel molecular contributors involved in RA initiation and progression using systems biology approaches will open up potential therapeutic strategies. The bioinformatics method allows the detection of associated miRNA-mRNA as both therapeutic and prognostic targets for RA.

Methods: This research used a system biology approach based on a systematic re-analysis of the RA-related microarray datasets in the NCBI Gene Expression Omnibus (GEO) database to find out deregulated miRNAs. We then studied the deregulated miRNA-mRNA using Enrichr and Molecular Signatures Database (MSigDB) to identify novel RA-related markers followed by an overview of miRNA-mRNA interaction networks and RA-related pathways.

Results: This research mainly focused on mRNA and miRNA interactions in all tissues and blood/serum associated with RA to obtain a comprehensive knowledge of RA. Recent systems biology approach analyzed seven independent studies and presented important RA-related deregulated miRNAs (miR-145-5p, miR-146a-5p, miR-155-5p, miR-15a-5p, miR-29c-3p, miR- 103a-3p, miR-125a-5p, miR-125b-5p, miR-218); upregulation of miR-125b is shown in the study (GSE71600). While the findings of the Enrichr showed cytokine and vitamin D receptor pathways and inflammatory pathways. Further analysis revealed a negative correlation between the vitamin D receptor (VDR) and miR-125b in RA-associated gene expression.

Conclusion: Since vitamin D is capable of regulating the immune homeostasis and decreasing the autoimmune process through its receptor (VDR), it is regarded as a potential target for RA. According to the results obtained, a comparative correlation between negative expression of the vitamin D receptor (VDR) and miR-125b was suggested in RA. The increasing miR-125b expression would reduce the VitD uptake through its receptor.

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<![CDATA[Cholesterol: A Prelate in Cell Nucleus and its Serendipity]]>https://www.eurekaselect.comarticle/105775 <![CDATA[Breast Cancer Detection and Classification using Traditional Computer Vision Techniques: A Comprehensive Review]]>https://www.eurekaselect.comarticle/105668 <![CDATA[Gastric Tract Infections Detection and Classification from Wireless Capsule Endoscopy using Computer Vision Techniques: A Review]]>https://www.eurekaselect.comarticle/106121 <![CDATA[Data Tagging in Medical Images: A Survey of the State-of-Art]]>https://www.eurekaselect.comarticle/104625 <![CDATA[MicroRNA-372-3p Predicts Response of TACE Patients Treated with Doxorubicin and Enhances Chemosensitivity in Hepatocellular Carcinoma]]>https://www.eurekaselect.comarticle/106664

Objective: This study aims to investigate the potential role of miR-372-3p in enhancing Dox effects on HCC cell line (HepG2). Additionally, the correlation between miR-372-3p and HCC patients who received Transarterial Chemoembolization (TACE) with Dox treatment has been analyzed.

Methods: Different cell processes were elucidated by cell viability, colony formation, apoptosis and wound healing assays after miR-372-3p transfection in HepG2 cells Furthermore, the miR-372-3p level has been estimated in the blood of primary HCC patients treated with TACE/Dox by quantitative real-time PCR assay. Receiver Operating Curve (ROC) analysis for serum miR-372-3p was constructed for its prognostic significance. Finally, the protein level of Mcl-1, the anti-apoptotic player, has been evaluated using western blot.

Results: We found a significantly higher level of miR-372-3p in the blood of the responder group of HCC patients who received TACE with Dox than of non-responders. Ectopic expression of miR-372-3p reduced cell proliferation, migration and significantly induced apoptosis in HepG2 cells which was coupled with a decrease of anti-apoptotic protein Mcl-1.

Conclusion: Our study demonstrated that miR-372-3p acts as a tumor suppressor in HCC and can act as a predictor biomarker for drug response. Furthermore, the data referred for the first time its potential role in drug sensitivity that might be a therapeutic target for HCC.]]> <![CDATA[Targeted Protein Degradation: An Emerging Therapeutic Strategy in Cancer]]>https://www.eurekaselect.comarticle/105757 <![CDATA[Repurposing Drugs for Skin Cancer]]>https://www.eurekaselect.comarticle/103105 <![CDATA[PD1 and PD-L1 Inhibitors for the Treatment of Kidney Cancer: The Role of PD-L1 Assay]]>https://www.eurekaselect.comarticle/105457Background: Immune checkpoint inhibitors targeting the programmed death receptor ligand 1 (PD-L1)/programmed death receptor 1 (PD-1) pathway represent a drastic change in the treatment landscape of RCC resulting in a dynamic and evolving scenario. There is an urgent need for predictive biomarkers of response to provide a personalized therapeutic strategy for individual patients.

Objective: In this review, we focused on trials that investigated the administration of a PD-1 and PDL1 inhibitor alone or in combination with another agent and compared the different assays applied in each trial to evaluate the role of PD-L1 as a prognostic and predictive biomarker.

Conclusion: So far, the use of PD-L1 expression alone is not sufficient to predict treatment response and present many limitations: the lack of consensus between different methodologies on biomarker assessment, the heterogeneity of PD-L1 between primary tumors and metastatic sites, different criteria of response to therapy (RECIST vs. irRECIST), the complex interplay with inflammatory components, previous treatments, administration of antibiotic therapy. Combinations of different biomarkers and biological features, such as gene expression associated with angiogenesis, immune response and myeloid inflammation are promising biological variables that need to be validated in the context of prospective clinical trials.

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<![CDATA[PET/CT and the Response to Immunotherapy in Lung Cancer]]>https://www.eurekaselect.comarticle/103106Objective: In recent years, the introduction of immune checkpoint inhibitors has significantly changed the outcome of patients affected by lung cancer and cutaneous melanoma. Although the clinical advantages, the selection of patients and the evaluation of response to immunotherapy remain unclear, the immune-related Response Evaluation Criteria in Solid Tumor (irRECIST) was proposed as an update of the RECIST criteria for the assessment of response to immunotherapy. However, morphological images cannot predict early response to therapy that represents a challenge in clinical practice. 18F-FDG PET/CT before and after immunotherapy has an indeterminate role, demonstrating ambiguous results due to inflammatory effects secondary to activation of the immune system. The aim of the present review was to analyze the role of PET/CT as a guide for immunotherapy, by analyzing the current status and future perspectives.

Methods: A literature search was conducted in order to select all papers that discussed the role of PET/CT with FDG or other tracers in the evaluation or prediction of response to immunotherapy in lung cancer patients.

Results: Many papers are now available. Many clinical trials have demonstrated the efficacy of immunotherapy in lung cancer patients. FDG PET/CT can be used for the prediction of response to immunotherapy, while its utility for the evaluation of response is not still clearly reported. Moreover, the standardization of FDG PET/CT interpretation is missing and different criteria, such as information, have been investigated until now.

Conclusion: The utility of FDG PET/CT for patients with lung cancer undergoing immunotherapies is still preliminary and not well addressed. New agents for PET are promising, but large clinical trials are mandatory.

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<![CDATA[The Potential of Flavonoids and Tannins from Medicinal Plants as Anticancer Agents]]>https://www.eurekaselect.comarticle/106666 <![CDATA[The Important Role of Oncolytic Viruses in Common Cancer Treatments]]>https://www.eurekaselect.comarticle/104396 <![CDATA[Immunoliposomes: Synthesis, Structure, and their Potential as Drug Delivery Carriers]]>https://www.eurekaselect.comarticle/104878 <![CDATA[Gold Nanoparticles; Potential Nanotheranostic Agent in Breast Cancer: A Comprehensive Review with Systematic Search Strategy]]>https://www.eurekaselect.comarticle/107246Background: Breast cancer is a heterogeneous disease typically prevalent among women and is the second-largest cause of death worldwide. Early diagnosis is the key to minimize the cancer-induced complication, however, the conventional diagnostic strategies have been sluggish, complex, and, to some extent, non-specific. Therapeutic tools are not so convenient and side effects of current therapies offer the development of novel theranostic tool to combat this deadly disease.

Objective: This article aims to summarize the advances in the diagnosis and treatment of breast cancer with gold nanoparticles (GNP or AuNP).

Methods: A systematic search was conducted in the three popular electronic online databases including PubMed, Google Scholar, and Web of Science, regarding GNP as breast cancer theranostics.

Results: Published literature demonstrated that GNPs tuned with photosensitive moieties, nanomaterials, drugs, peptides, nucleotide, peptides, antibodies, aptamer, and other biomolecules improve the conventional diagnostic and therapeutic strategies of breast cancer management with minimum cytotoxic effect. GNP derived diagnosis system assures reproducibility, reliability, and accuracy cost-effectively. Additionally, surface-modified GNP displayed theranostic potential even in the metastatic stage of breast cancer.

Conclusion: Divergent strategies have shown the theranostic potential of surface tuned GNPs against breast cancer even in the metastatic stage with minimum cytotoxic effects both in vitro and in vivo.

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<![CDATA[Sphingosine Analogs and Protein Phosphatase 2A as a Molecular Targeted Cancer Therapy: A Mini Systematic Review]]>https://www.eurekaselect.comarticle/106332Background: Regulation of protein phosphatase 2A (PP2A) plays an important role in hematologic and solid neoplasms. Therefore, the use of sphingosine analogs as anti-neoplastic drugs has shown potential due to their role as PP2A activators.

Objective: Investigation of whether sphingosine analogs bind to endogenous inhibitor proteins of PP2A, such as I2 PP2A/SET and/or CIP2A, and whether this binding reactivates PP2A, allowing it to resume its role as a tumor suppressor.

Methods: Literature from the PubMed database was searched and those articles related to PP2A and sphingosine analogs were reviewed.

Results: Utilization of sphingosine analogs in hematologic and solid neoplasms revealed numerous mechanisms of inducing cell death. Regulation of PP2A through modulation of I2 PP2A/SET and/or CIP2A was demonstrated in a variety of neoplastic processes; however, unique mechanisms such as cell necrosis via the production of reactive oxygen species was also appreciated.

Conclusion: Only certain malignancies expressed endogenous inhibitor proteins, yet sphingosine analogs were able to induce cell death in neoplasms that did not express these proteins. This suggests that sphingosine analogs may be utilized for anti-neoplastic therapy via reactivation of PP2A however, it is not the exclusive mechanism for inducing cell death. Further investigation of sphingosine analogs as a novel or adjunctive chemotherapeutic treatment is warranted.

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<![CDATA[MicroRNAs as Therapeutic Targets for Anticancer Drugs in Lung Cancer Therapy]]>https://www.eurekaselect.comarticle/107358 <![CDATA[Schiff Bases and Complexes: A Review on Anti-Cancer Activity]]>https://www.eurekaselect.comarticle/106427 <![CDATA[Elevated O-GlcNAcylation Promotes Malignant Phenotypes of Hypopharyngeal Squamous Cell Carcinoma by Stabilizing Nrf2 through Regulation of the PI3K/Akt Pathway]]>https://www.eurekaselect.comarticle/107357Background and Purpose: O-GlcNAcylation is a significant protein posttranslational modification with O-linked β-N-acetylglucosamine (GlcNAc) for intracellular signaling. Elevated O-GlcNAcylation contributes to cell proliferation, cell migration, cell apoptosis and signal transduction in various cancers. However, the expression level and functional role of O-GlcNAcylation in Hypopharyngeal Squamous Cell Carcinoma (HSCC) is not clearly elucidated. Nuclear factor erythroid-2-related factor 2 (Nrf2) is a master transcriptional factor that has been found to be aberrantly activated in HSCC. Here, we provide a molecular rationale between O-GlcNAcylation and Nrf2 in HSCC patients.

Methods: The protein levels of O-GlcNAcylation and Nrf2 in HSCC tissues were detected by immunohistochemistry technique and western blot analysis. Then, O‐GlcNAcylation knockdown HSCC cells were applied in this study. Cell proliferation was detected by CCK8, colony-forming analysis, and cell cycle assays. Cell migration and invasion ability was evaluated by transwell assays. Cell apoptosis was measured by TUNEL analysis.

Results: O-GlcNAcylation was obviously up-regulated in HSCC tissues, which correlated with tumor size and lymph node metastasis. In addition, the protein level of Nrf2 was found to positively correlate with the expression of O‐GlcNAcylation both in vivo and in vitro. Knockdown of O-GlcNAcylation significantly inhibited HSCC cell growth, suppressed cell migration, and promoted cell apoptosis, whereas overexpression of Nrf2 reversed these phenotypes. Mechanismly, the upregulation of O-GlcNAcylation promoted the phosphorylation of Akt, leading to the stabilization of Nrf2; this could be attenuated by inhibition of the PI3K/Akt signaling pathway.

Conclusion: Here, we provide a molecular association between O-GlcNAcylation and Nrf2 in HSCC patients, thus providing valuable therapeutic targets for the disease.

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<![CDATA[Assessment of Ploy Dopamine Coated Fe<sub>3</sub>O<sub>4</sub> Nanoparticles for Melanoma (B16-F10 and A-375) Cells Detection]]>https://www.eurekaselect.comarticle/106578Objective: Polydopamine coated iron oxide nanoparticles (Fe3O4@PDA NPs) were synthesized, characterized, and their MR imaging contrast agents and photothermal potency were evaluated on melanoma (B16-F10 and A-375) cells and normal skin cells. To this end, MTT assay, Fe concentration, and MR imaging of both coated and uncoated NPs were assessed in C57BL/6 mice.

Methods: Fe3O4 nanoparticles were synthesized using co-precipitation, and coated with polydopamine. The cytotoxicity of Fe3O4 and Fe3O4@PDA NPs on melanoma cells, with different concentrations, were obtained using MTT assay. MR images and Fe concentrations of nanoprobe and nanoparticles were evaluated under in vivo conditions.

Results: Findings indicated that uncoated Fe3O4 showed the highest toxicity in animal (B16-F10) cells at 450μg/ml after 72h, while the highest toxicity in human (A-375) cells were observed at 350μg/ml. These nanoparticles did not reveal any cytotoxicity to normal skin cells, despite having some toxicity features in A-375 cells. MR image signals in the tumor were low compared with other tissues. The iron concentration in the tumor was higher than that of other organs.

Conclusion: It is concluded that the cytotoxicity of Fe3O4@PDA was found to be significantly lower than uncoated nanoparticles (p <0.001), which allows some positive effects on reducing toxicity. The prepared nanoprobe may be used as a contrast agent in MR imaging.

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<![CDATA[Salidroside - Can it be a Multifunctional Drug?]]>https://www.eurekaselect.comarticle/107244Background: Salidroside is a glucoside of tyrosol found mostly in the roots of Rhodiola spp. It exhibits diverse biological and pharmacological properties. In the last decade, enormous research is conducted to explore the medicinal properties of salidroside; this research reported many activities like anti-cancer, anti-oxidant, anti-aging, anti-diabetic, anti-depressant, anti-hyperlipidemic, anti-inflammatory, immunomodulatory, etc.

Objective: Despite its multiple pharmacological effects, a comprehensive review detailing its metabolism and therapeutic activities is still missing. This review aims to provide an overview of the metabolism of salidroside, its role in alleviating different metabolic disorders, diseases and its molecular interaction with the target molecules in different conditions. This review mostly concentrates on the metabolism, biological activities and molecular pathways related to various pharmacological activities of salidroside.

Conclusion: Salidroside is produced by a three-step pathway in the plants with tyrosol as an intermediate molecule. The molecule is biotransformed into many metabolites through phase I and II pathways. These metabolites, together with a certain amount of salidroside may be responsible for various pharmacological functions. The salidroside based inhibition of PI3k/AKT, JAK/ STAT, and MEK/ERK pathways and activation of apoptosis and autophagy are the major reasons for its anti-cancer activity. AMPK pathway modulation plays a significant role in its anti-diabetic activity. The neuroprotective activity was linked with decreased oxidative stress and increased antioxidant enzymes, Nrf2/HO-1 pathways, decreased inflammation through suppression of NF-κB pathway and PI3K/AKT pathways. These scientific findings will pave the way to clinically translate the use of salidroside as a multi-functional drug for various diseases and disorders in the near future.

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<![CDATA[Effect of Fruit Secondary Metabolites on Melanoma: A Systematic Review of <i>In vitro</i> Studies]]>https://www.eurekaselect.comarticle/100215Background: Melanoma is a highly aggressive form of skin cancer and is responsible for the majority of the deaths related to this pathology. Recently, different studies have identified naturally occurring compounds of fruits with chemopreventive action. This systematic review aims to investigate the protective role of fruit phytochemicals against melanoma skin cancer from in vitro studies.

Methods: The articles were selected using the search terms string "skin neoplasms" OR “melanoma” AND “fruit” in the following databases: Pubmed/Medline, Bireme, Web of Science and ScienceDirect.

Results: Out of an initial database search of 391 titles and/or abstracts, 115 full-text articles were eligible and after final evaluation 49 were selected for further assessment. Almost all analysed articles reveal that compounds of different classes (alkaloid, alkane, benzopyrone, cyclopenta[b]benzofuran, ester, flavonoid, tocotrienols, phenolic, phenylpropanoid, phloroglucinol derivative, terpenoids and betalain) possess anti-melanoma in vitro activity. The benzopyrone (α-mangostin) and stilbene (resveratrol) were effective in inhibiting melanoma cell metastasis, essential to stop the progression of malignant cells.

Conclusion: Phytochemicals that possess anticancer properties are present in both, common and exotic fruits. Some of these novel compounds are considered as promising starting points for the discovery of effective new drugs.

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<![CDATA[Current Treatment for Cervical Cancer: An Update]]>https://www.eurekaselect.comarticle/104741 <![CDATA[Lipid Nanoparticles as a Skin Wound Healing Drug Delivery System: Discoveries and Advances]]>https://www.eurekaselect.comarticle/105884 <![CDATA[Immunotherapy and Radiation Therapy in Renal Cell Carcinoma]]>https://www.eurekaselect.comarticle/105147Background: The management of renal cell carcinoma is rapidly evolving and immunotherapy, mostly consisting of immune checkpoint inhibitors, is revolutionizing the treatment scenario of metastatic patients. Novel fractionation schedules of radiotherapy, consisting of high doses in few fractions, can overcome the radioresistance of this tumor. Localized radiotherapy is associated with a systemic effect, known as the abscopal effect. This effect mediated by the immune system can be enhanced associating radiotherapy with immunotherapy.

Objective: In this review, we explore the role of radiotherapy and immunotherapy in RCC, the rationale of combining these strategies and the on-going clinical trials investigating combinations of these two treatment modalities.

Conclusion: Combining immunotherapy and radiotherapy has a strong rationale and pre-clinical studies support their association because it can overcome the immunosuppression of the tumor microenvironment and increase the anti-tumor immune response. More clinical evidence, deriving from onclinical trials, are needed to prove the efficacy and safety of these treatments combined.

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<![CDATA[An Overview of Piperazine Scaffold as Promising Nucleus for Different Therapeutic Targets]]>https://www.eurekaselect.comarticle/105889 <![CDATA[Zidovudine Glycosylation by Filamentous Fungi Leads to a Better Redox Stability and Improved Cytotoxicity in B16F10 Murine Melanoma Cells]]>https://www.eurekaselect.comarticle/106081Background: The strategic development of therapeutic agents, capable of being targeted at their active sites, has been a major goal in treatment of cancer. The delivery of drugs for tumors has as its main challenge the development of safe and effective drugs, since the goal of chemotherapy is to eliminate the tumor completely without affecting healthy cells. The aim of present study was to investigate the antioxidant, anticancer activities of zidovudine and its α-O-glycosylated derivative obtained by biosynthesis of a filamentous fungi, Cunninghamela echinulata.

Methods: An evaluation of the cytotoxic potential of zidovudine and its α-O-glycosylated was performed in fibroblasts and melanoma cells by the tetrazolium reduction method (MTT) and the antioxidant activity of this derivative was observed.

Results: The antioxidant activity of zidovudine demonstrated an electrochemical oxidation potential of 0.91V, while the α-O-glycosylated derivative did not exhibit any antioxidant activity. The zidovudine exhibited low cytotoxicity for melanoma and fibroblast cells, while the α-O-glycosylated derivative presented better cytotoxicity on melanoma cells at a concentration of 10mg. mL-1.

Conclusion: This study demonstrates the specific cytotoxicity of the glycoconjugate and suggests that glycosylation by biosynthesis can be a useful strategy for obtaining new anticancer compounds.

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<![CDATA[Molecular Docking of 4-ethoxychalcones on Oxidoreductase/Pirin Inhibitors and Cytotoxic Evaluation on Breast/Skin Cancer Cell Lines]]>https://www.eurekaselect.comarticle/104057Background: The role of α, β unsaturated propenone derivatives, has attracted the chemists for its biological importance. An attempt is made to reveal the interaction between breast and skin cancer cell lines with the help of molecular docking studies.

Objective: The study aimed to synthesize and characterize 4-ethoxychalcones for testing breast and skin cancer targets.

Methods: A series of chalcone analogues starting from 4-ethoxyacetophenone and substituted aromatic aldehydes were synthesized, well-characterized and evaluated for their in vitro anticancer activities against human breast cancer (MDA-MB-231) and human metastatic melanoma (A-375) cell lines by MTT assay. Docking simulation was performed to study the drug-receptor interaction of chalcone scaffold on the active site of target inhibitor bound to cytochrome P450 family oxidoreductase for breast cancer and Pirin inhibiting target for skin cancer, respectively.

Results and Discussion: After performing cytotoxic evaluation, it was observed that compounds having a substitution at the para position showed better results compared to ortho and meta positions for both the cell lines. Molecular docking studies revealed different types of interactions with selected oxidoreductase and Pirin inhibiting targets. Ligand-protein interactions and morphological changes are monitored by molecular dynamics.

Conclusion: The presence of electron-withdrawing and donating groups on ring B marginally affected IC50 and docking scores. The stability of the binding mode of ligands having high inhibitory efficiency for compounds 8 and 10 predicted by docking studies was confirmed by molecular dynamics simulation. The pharmacokinetic parameters were found to be within the acceptable range. Further molecular dynamics study would provide the necessary information.

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<![CDATA[Pyrimidinone Associated Triazole Carboxamides: Synthesis, Characterization, Cytotoxicity and DNA Binding Studies]]>https://www.eurekaselect.comarticle/97650Background: Pyrimidinones and its derivatives are present in many anti-cancer agents. It has been reported that these substances were proven to have significant activities against different types of human cancers. The incorporation of [1,2,3]-triazole, a nitrogen-rich unit not only increases the efficacy but also increases the lipophilicity of the drug molecule. As our research was to synthesize newer molecules of effective cytotoxicity, we focused on pyrimidinone and [1,2,3]-triazoles systems, as important scaffolds with the expectation of potential cytotoxic properties.

Methods: Novel series of [1,2,3]-triazole carboxamides (5a-j) were synthesized, starting from 3-(2- chloroethyl)-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one. The structure of all the synthesized compounds was elucidated based on IR, 1H-NMR, 13C-NMR and LC-MS data. Compounds were focused for their in vitro cytotoxicity against A375 melanoma cancer cell lines, MDA-MB-231 breast cancer cell lines and HEK 293-Human embryonic kidney cell lines using colorimetric MTT assay. The potent compound was evaluated for the DNA binding studies.

Results: Most of the Pyrimidinone conjugated [1,2,3]-triazole carboxamides found to be selective towards melanoma cancer cell lines than breast cancer cell lines. Compounds 5d, 5i and 5b were effective against A375 cancer cell lines and are found to be non-toxic against HEK 293-Human embryonic kidney cell lines. The potent compound 5d showed good intrinsic binding constant (Kb) value 3.12 x 103 M-1 in UV based DNA titration.

Conclusion: Newly synthesized Pyrimidinone conjugated [1,2,3]-triazole carboxamide derivatives showed the significant cytotoxicity and the potent compound showed good intrinsic binding constant in UV based DNA titration.

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<![CDATA[A Current Review on Drug Loaded Nanofibers: Interesting and Valuable Platform for Skin Cancer Treatment]]>https://www.eurekaselect.comarticle/103787Background: Nanofibers are used in topical medication for various skin diseases like wound healing, skin cancer and others. Non-melanoma skin cancers (NMSCs) are the most widely distributed diseases in the world, of which 99% of people are affected by either basal cell carcinomas (BCCs) or squamous cell carcinomas (SCCs) of the skin. Skin malignancy is caused by direct sun exposure and regular application of unsafe restorative items on the skin.

Objective: This review presents the use of nanofibers in skin cancer treatment and advances made in skin cancer treatment.

Methods: There are various methods used in the production of nanofibers such as bicomponent extrusion, phase separation, template synthesis, drawing, electrospinning, and others. Electrospinning is the most widely used technique for nanofiber fabrication. The nanofibers are produced in nanometer size range and mostly used in medication because of their low thickness, large surface area per unit mass and porosity. Nanofibers are also used as drug delivery system for sustaining the action of drugs or medicaments.

Results: Nanofibers enhance the permeation and availability of those drugs having low bioavailability and low permeability. Nanofibers increase the sustainability of the drugs up to 10 days.

Conclusion: Skin cancer is the abnormal growth of skin cells in the body influencing people of all colours and skin. In this review paper, the definition and production techniques of nanofibers and drugs used in skin cancer treatment and the relation between skin cancer and nanofiber are illustrated in detail. With the help of different techniques and drugs, the risk of non-melanoma skin cancer is reduced.

Lay Summary: The risk of skin cancer and other skin problems is increasing day by day. In a previous study we found that the nanofibers are less used as a topical delivery system. We have studied the nanofibers as a drug delivery system in the treatment of skin cancer by using different drugs. According our study nanofibers are most useful in skin drug delivery and if the nanofiber, are merging with other drug delivery system like nanoparticles, it may maximize the output of drug into skin. The significance of this study is, to explain all information about nanofibers in skin cancer.

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<![CDATA[Immune Checkpoint Inhibitors in Patients with Recurrent Hepatocellular Carcinoma after Liver Transplantation: A Case Report and Literature Review]]>https://www.eurekaselect.comarticle/106787Background: Immune checkpoint modulators, such as the programmed death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitor, cytotoxic T-Lymphocyte-associated antigen 4 (CTLA-4) inhibitor have been investigated with encouraging results for hepatocellular carcinoma (HCC). However, the safety of this strategy in patients with previous liver transplantation (LT) is not well studied.

Objective: To explore the safety and feasibility of immune checkpoints inhibitors in recurrent and metastatic HCC patients on a background of LT.

Methods: A case of recurrent, refractory, metastatic HCC after LT, where PD-1 inhibitor was initiated, was described and related literature was reviewed.

Results: There was complete remission in lung metastases and the partial radiological response of metastatic retroperitoneal lymph node to the drug with no liver graft rejection after 13 cycles of PD- 1 inhibitor injection. PD-1inhibitor, at least in this patient, was verified to play an important role in controlling tumor progression and prolonging patient survival.

Conclusion: This novel drug might be a useful method to allow doctors to guarantee a better chance for long-term survival in recurrent, metastatic HCC patients with the previous LT. However, it should be used with caution in allograft recipients due to the risk of acute graft rejection, further larger, prospective studies are needed to determine optimal immunomodulatory therapy to achieve optimal anti-tumor efficacy with transplant liver preservation.

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<![CDATA[Targeting MUC15 Protein in Cancer: Molecular Mechanisms and Therapeutic Perspectives]]>https://www.eurekaselect.comarticle/107017 <![CDATA[Amino Acids Sequence-based Analysis of Arginine Deiminase from Different Prokaryotic Organisms: An In Silico Approach]]>https://www.eurekaselect.comarticle/105441Background: Arginine deiminase is a bacterial enzyme, which degrades L-arginine. Some human cancers such as hepatocellular carcinoma (HCC) and melanoma are auxotrophic for arginine. Therefore, PEGylated arginine deiminase (ADI-PEG20) is a good anticancer candidate with antitumor effects. It causes local depletion of L-arginine and growth inhibition in arginineauxotrophic tumor cells. The FDA and EMA have granted orphan status to this drug. Some recently published patents have dealt with this enzyme or its PEGylated form.

Objective: Due to increasing attention to it, we aimed to evaluate and compare 30 arginine deiminase proteins from different bacterial species through in silico analysis.

Methods: The exploited analyses included the investigation of physicochemical properties, multiple sequence alignment (MSA), motif, superfamily, phylogenetic and 3D comparative analyses of arginine deiminase proteins thorough various bioinformatics tools.

Results: The most abundant amino acid in the arginine deiminase proteins is leucine (10.13%) while the least amino acid ratio is cysteine (0.98%). Multiple sequence alignment showed 47 conserved patterns between 30 arginine deiminase amino acid sequences. The results of sequence homology among 30 different groups of arginine deiminase enzymes revealed that all the studied sequences located in amidinotransferase superfamily. Based on the phylogenetic analysis, two major clusters were identified. Considering the results of various in silico studies; we selected the five best candidates for further investigations. The 3D structures of the best five arginine deiminase proteins were generated by the I-TASSER server and PyMOL. The RAMPAGE analysis revealed that 81.4%-91.4%, of the selected sequences, were located in the favored region of arginine deiminase proteins.

Conclusion: The results of this study shed light on the basic physicochemical properties of thirty major arginine deiminase sequences. The obtained data could be employed for further in vivo and clinical studies and also for developing the related therapeutic enzymes.

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<![CDATA[<i>In silico</i> and <i>In vitro</i> Investigation of a Likely Pathway for Anti-Cancerous Effect of Thrombocidin-1 as a Novel Anticancer Peptide]]>https://www.eurekaselect.comarticle/104648Background: Antimicrobial and antifungal activities of Thrombocidin-1 (TC-1) is shown previously, however, the anti-cancerous feature of this peptide is still uncovered.

Objective: The objective is to evaluate anti-cancerous feature of recombinant TC-1.

Methods: In this study, based on the significant similarity of rTC-1 and IL-8 in case of coding sequence, tertiary structure, and also docking and molecular dynamic simulation (MD) results with CXCR1, a receptor which has positive correlation with different cancers, a likely pathway for anticancerous effect of rTC-1 was proposed. In addition, the coding sequence of TC-1+6xhistidine (rTC-1) was inserted into the pET22b(+) vector and cloned and expressed by E. coli BL21 and finally purified through nickel affinity column. Afterward, the retrieved rTC-1 was used in MTT assay against mouse colon adenocarcinoma, hepatocellular carcinoma, chondrosarcoma, mouse melanoma, and breast adenocarcinoma cell lines to investigate its probable anticancer application.

Results: Docking and MD simulation results showed that rTC-1 and IL-8 share almost the same residues in the interaction with CXCR1 receptor. Besides, the stability of the rTC-1_CXCR11-38 complex was shown during 100ns MD simulation. In addition, the successful expression and purification of rTC-1 depict an 8kD peptide. The IC50 results of MTT assay revealed that rTC-1 has cytotoxic effect on C26-A and SW1353 cancerous cell lines.

Conclusion: Therefore, apart from probable anti-cancerous effect of rTC-1 on C26-A and SW1353 cell lines, this peptide may be able to mimic the anti-cancerous pathway of IL-8.

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<![CDATA[Advances in the use of MOFs for Cancer Diagnosis and Treatment: An Overview]]>https://www.eurekaselect.comarticle/105682 <![CDATA[Targeting Autophagic Pathways by Plant Natural Compounds in Cancer Treatment]]>https://www.eurekaselect.comarticle/106310 <![CDATA[The Epigenetic Modification of Epigallocatechin Gallate (EGCG) on Cancer]]>https://www.eurekaselect.comarticle/106314Among the major components of green tea, epigallocatechin-3-gallate (EGCG) is the most effective for its anti-cancer characteristics. The bulk of studies provide the mechanisms of suppressive function of EGCG are involved in alteration of cancer cell cycle, development, and apoptosis through activation/inhibition of several signal pathways.

Another mechanism that explains the multiple effects exerted by EGCG in cancer is the epigenetic change by DNA methylation or methyltransferases, histone acetylation or deacetylases, and no coding RNAs (micoRNAs). Furthermore, decontrolled expression of miRNA transcription has been tested to be directly regulated by oncogenic and tumor-suppressor transcription factors. Recently, several proteins have been identified as miRNA direct interactors by EGCG. However, the mechanisms explaining the action of miRNA being modulated by EGCG have not been completely understood yet. This review summarizes the state of epigenetic change being modulated by EGCG in a variety of cancers and oncogenic and tumor-suppressor transcription factors.

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<![CDATA[Current and Future Prospective of a Versatile Moiety: Imidazole]]>https://www.eurekaselect.comarticle/106986 <![CDATA[Nano-Carriers of Combination Tumor Physical Stimuli-Responsive Therapies]]>https://www.eurekaselect.comarticle/106882via the platform of nanocarriers into combination TPSRTs, which include Photothermal Therapy (PTT) with Magnetic Hyperthermia Therapy (MHT), PTT with Sonodynamic Therapy (SDT), MHT with Photodynamic Therapy (PDT), and PDT with PTT. To achieve such therapies, it requires to fully utilize the versatile functions of a specific nanocarrier, which depend on a pellucid understanding of the traits of those nanocarriers. This review covers the principles of different TPSRTs and their combinations, summarizes various types of combination TPSRTs nanocarriers and their therapeutic effects on tumors, and discusses the current disadvantages and future developments of these nanocarriers in the application of combination TPSRTs.]]> <![CDATA[Metastatic Brain Tumors: To Treat or Not to Treat, and with What?]]>https://www.eurekaselect.comarticle/95166 <![CDATA[Design, Synthesis and Biological Evaluation of Novel 1,2,5-Oxadiazol-3- Carboximidamide Derivatives as Indoleamine 2, 3-Dioxygenase 1 (IDO1) Inhibitors]]>https://www.eurekaselect.comarticle/107087Background and Objective: Indoleamine-2,3-dioxygenase 1 (IDO1), which catalyzes the degradation of L-tryptophan (L-Trp) to N-formyl kynurenine (NFK) in the first and rate-limiting step of Kynurenine (KYN) pathway has been identified as a promising therapeutic target for cancer immunotherapy. The small molecule Epacadostat developed by Incyte Corp is the most advanced IDO1 inhibitor in clinical trials.

Methods: In this study, various amidine derivatives were individually installed as the polar capping group onto the amino ethylene side chain to replace the sulfamoylamino moiety of Epacadostat to develop novel IDO1 inhibitors. A series of novel 1,2,5-oxadiazol-3-carboximidamide derivatives were designed, prepared, and evaluated for their inhibitory activities against human IDO1 enzyme and cellular IDO1.

Results: In vitro human IDO1 enzyme and cellular IDO1 assay results demonstrate that the inhibitory activities of compound 13a and 13b were comparable to Epacadostat, with the enzymatic IC50 values of 49.37nM and 52.12nM and cellular IC50 values of 12.34nM and 14.34nM, respectively. The anti-tumor efficacy of 13b is slightly better than Epacadosta in Lewis Lung Cancer (LLC) tumor-bearing mice model.

Conclusion: 13b is a potent IDO1 inhibitor with therapeutic potential in tumor immunotherapy.

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<![CDATA[Melanoma Detection and Classification using Computerized Analysis of Dermoscopic Systems: A Review]]>https://www.eurekaselect.comarticle/103149 <![CDATA[Computer-aided Diagnosis of Skin Cancer: A Review]]>https://www.eurekaselect.comarticle/104013 <![CDATA[Computer-aided Diagnosis of Melanoma: A Review of Existing Knowledge and Strategies]]>https://www.eurekaselect.comarticle/102867 <![CDATA[Promising Strategies for Overcoming BRAF Inhibitor Resistance Based on Known Resistance Mechanisms]]>https://www.eurekaselect.comarticle/105981

Prospect: In this review, we discuss promising strategies for overcoming drug resistance and highlighting the prospects for discovering strategies to counteract BRAF inhibitor resistance.]]>
<![CDATA[Synthesis and Applications of Hydrogels in Cancer Therapy]]>https://www.eurekaselect.comarticle/103749 <![CDATA[Exploring siRNA Umpired Nanogels: A Tale of Barrier Combating Carrier]]>https://www.eurekaselect.comarticle/105883 <![CDATA[Metalloproteinases Suppression Driven by the Curcumin Analog DM-1 Modulates Invasion in BRAF-Resistant Melanomas]]>https://www.eurekaselect.comarticle/104603

Methods: Evaluated DM-1 stability and cytotoxic effects for BRAFi-sensitive and resistant melanomas, as well as the role in the metalloproteinases modulation.

Results: DM-1 showed growth inhibitory potential for melanoma cells, demonstrated by reduction of colony formation, migration and endothelial tube formation, and cell cycle arrest. Subtoxic doses were able to downregulate important Metalloproteinases (MMPs) related to invasiveness, such as MMP-1, -2 and -9. Negative modulations of TIMP-2 and MMP-14 reduced MMP-2 and -9 activity; however, the reverse effect is seen when increased TIMP-2 and MMP-14 resulted in raised MMP-2.

Conclusion: These findings provide essential details into the functional role of DM-1 in melanomas, encouraging further studies in the development of combinatorial treatments for melanomas.]]>
<![CDATA[Roles of Medicinal Plants and Constituents in Gynecological Cancer Therapy: Current Literature and Future Directions]]>https://www.eurekaselect.comarticle/105854Gynecologic cancers, including cervical, primary peritoneal, ovarian, uterine/endometrial, vaginal and vulvar cancers and gestational trophoblastic disease, are characterized by abnormal cell proliferation in female reproductive cells. Due to the variable pathology of these cancers and the lack of appropriate screening tests in developing countries, cancer diagnosis can be reported in advanced stages in most women and this situation adversely affects prognosis and clinical outcomes of illness. For this reason, many researchers in the field of gynecological oncology have carried out many studies.

The treatment of various gynecological problems, which cause physical, biological and psychosocial conditions such as fear, shame, blame and anger, has been important throughout the history. Treatment with herbs has become popular nowadays due to the serious side effects of the synthetic drugs used in treatment and the medical and economical problems caused by them. Many scientists have identified various active drug substances through in vivo and in vitro biological activity studies on medicinal plants from the past to the present. While the intrinsic complexity of natural product-based drug discoveries requires highly integrated interdisciplinary approaches, scientific and technological advances and research trends clearly show that natural products will be among the most important new drug sources in the future.

In this review, an overview of the studies conducted for the discovery of multitargeted drug molecules in the rational treatment of gynecological cancers is presented.

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<![CDATA[Curcumin Sensitizes Cancers Towards TRAIL-induced Apoptosis via Extrinsic and Intrinsic Apoptotic Pathways]]>https://www.eurekaselect.comarticle/104949 <![CDATA[Down-Regulation of DDR1 Induces Apoptosis and Inhibits EMT through Phosphorylation of Pyk2/MKK7 in DU-145 and Lncap-FGC Prostate Cancer Cell Lines]]>https://www.eurekaselect.comarticle/105753Background: In cancer cells, re-activation of Epithelial-Mesenchymal Transition (EMT) program through Discoidin Domain Receptor1 (DDR1) leads to metastasis. DDR1-targeted therapy with siRNA might be a promising strategy for EMT inhibition. Therefore, the aim of this study was to investigate the effect of DDR1 knockdown in the EMT, migration, and apoptosis of prostate cancer cells. For this purpose, the expression of DDR1 was down regulated by the siRNA approach in LNcap-FGC and DU-145 prostate cancer cells.

Methods: Immunocytochemistry was carried out for the assessment of EMT. E-cadherin, N-cadherin, Bax, Bcl2, and the phosphorylation level of Proline-rich tyrosine kinase 2 (Pyk2) and Map Kinase Kinase 7 (MKK7) was determined using the western blot. Wound healing assay was used to evaluate cell migration. Flow cytometry was employed to determine the apoptosis rate in siRNA-transfected cancer cells.

Results: Our findings showed that the stimulation of DDR1 with collagen-I caused increased phosphorylation of Pyk2 and MKK7 signaling molecules that led to the induction of EMT and migration in DU-145 and LNcap- FGC cells. In contrast, DDR1 knockdown led to significant attenuation of EMT, migration, and phosphorylation levels of Pyk2 and MKK7. Moreover, DDR1 knockdown via induction of Bax expression and suppression of Bcl-2 expression induces apoptosis.

Conclusion: Collectively, our results indicate that the DDR1 targeting with siRNA may be beneficial for the inhibition of EMT and the induction of apoptosis in prostate cancer.

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<![CDATA[Phanginin R Induces Cytoprotective Autophagy via JNK/c-Jun Signaling Pathway in Non-Small Cell Lung Cancer A549 Cells]]>https://www.eurekaselect.comarticle/105790Background: Cassane-type diterpenoids are widely distributed in the medical plants of genus Caesalpinia. To date, plenty of cassane diterpenoids have been isolated from the genus Caesalpinia, and some of them were documented to exhibit multiple biological activities. However, the effects of these compounds on autophagy have never been reported.

Objective: To investigate the effects and mechanisms of the cassane diterpenoids including Phanginin R (PR) on autophagy in Non-Small Cell Lung Cancer (NSCLC) A549 cells.

Methods: Western blot analysis and immunofluorescence assay were performed to investigate the effects of the compounds on autophagic flux in A549 cells. The pathway inhibitor and siRNA interference were used to investigate the mechanism of PR. MTT assay was performed to detect cell viability.

Results: PR treatment upregulated the expression of phosphatidylethanolamine-modified microtubule-associated protein Light-Chain 3 (LC3-II) in A549 cells. Immunofluorescence assay showed that PR treatment increased the production of red-fluorescent puncta in mRFP-GFP-LC3 plasmid-transfected cells, indicating PR promoted autophagic flux in A549 cells. PR treatment activated the c-Jun N-terminal Kinase (JNK) signaling pathway while it did not affect the classical Akt/mammalian Target of Rapamycin (mTOR) pathway. Pretreatment with the JNK inhibitor SP600125 or siRNA targeting JNK or c-Jun suppressed PR-induced autophagy. In addition, cotreatment with the autophagy inhibitor Chloroquine (CQ) or inhibition of the JNK/c-Jun signaling pathway increased PR-induced cytotoxicity.

Conclusion: PR induced cytoprotective autophagy in NSCLC A549 cells via the JNK/c-Jun signaling pathway, and autophagy inhibition could further improve the anti-cancer potential of PR.

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<![CDATA[Anti-Tumor Effects of Osthole on Different Malignant Tissues: A Review of Molecular Mechanisms]]>https://www.eurekaselect.comarticle/104902 <![CDATA[Plant Extracts as a Natural Source of Bioactive Compounds and Potential Remedy for the Treatment of Certain Skin Diseases]]>https://www.eurekaselect.comarticle/105890 <![CDATA[B7-H3-targeted Radioimmunotherapy of Human Cancer]]>https://www.eurekaselect.comarticle/96941Background: Targeted Radioimmunotherapy (RIT) is an attractive approach to selectively localize therapeutic radionuclides to malignant cells within primary and metastatic tumors while sparing normal tissues from the effects of radiation. Many human malignancies express B7-H3 on the tumor cell surface, while expression on the majority of normal tissues is limited, presenting B7-H3 as a candidate target for RIT. This review provides an overview of the general principles of targeted RIT and discusses publications that have used radiolabeled B7-H3-targeted antibodies for RIT of cancer in preclinical or clinical studies.

Methods: Databases including PubMed, Scopus, and Google Scholar were searched for publications through June 2018 using a combination of terms including “B7-H3”, “radioimmunotherapy”, “targeted”, “radiotherapy”, and “cancer”. After screening search results for relevancy, ten publications were included for discussion.

Results: B7-H3-targeted RIT studies to date range from antibody development and assessment of novel Radioimmunoconjugates (RICs) in animal models of human cancer to phase II/III trials in humans. The majority of clinical studies have used B7-H3-targeted RICs for intra- compartment RIT of central nervous system malignancies. The results of these studies have indicated high tolerability and favorable efficacy outcomes, supporting further assessment of B7-H3-targeted RIT in larger trials. Preclinical B7-H3-targeted RIT studies have also shown encouraging therapeutic outcomes in a variety of solid malignancies.

Conclusion: B7-H3-targeted RIT studies over the last 15 years have demonstrated feasibility for clinical development and support future assessment in a broader array of human malignancies. Future directions worthy of exploration include strategies that combine B7-H3- targeted RIT with chemotherapy or immunotherapy.

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<![CDATA[Modulation of Immuno-biome during Radio-sensitization of Tumors by Glycolytic Inhibitors]]>https://www.eurekaselect.comarticle/90858 <![CDATA[Molecular Docking Studies and Inhibition Properties of Some Antineoplastic Agents against Paraoxonase-I]]>https://www.eurekaselect.comarticle/104600Background: Currently, most of the drugs used in clinical applications show their pharmacological influences by inhibiting or activating enzymes. Therefore, enzyme inhibitors have an essential place in the drug design for many diseases.

Objective: The current study aimed to contribute to this growing drug design field (i.e., medicine discovery and development) by analyzing enzyme-drug interactions.

Methods: For this reason, Paraoxonase-I (PON1) enzyme was purified from fresh human serum by using rapid chromatographic techniques. Additionally, the inhibition effects of some antineoplastic agents were researched on the PON1.

Results: The enzyme was obtained with a specific activity of 2603.57 EU/mg protein. IC50 values for pemetrexed disodium, irinotecan hydrochloride, dacarbazine, and azacitidine were determined to be 9.63μM, 30.13μM, 53.31μM, and 21.00mM, respectively. These agents found to strongly inhibit PON1, with Ki constants ranging from 8.29±1.47μM to 23.34±2.71mM. Dacarbazine and azacitidine showed non-competitive inhibition, while other drugs showed competitive inhibition. Furthermore, molecular docking was performed using maestro for these agents. Among these, irinotecan hydrochloride and pemetrexed disodium possess the binding energy of -5.46 and -8.43 kcal/mol, respectively.

Conclusion: The interaction studies indicated that these agents with the PON1 possess binding affinity.

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<![CDATA[Gene Therapy (Part I)]]>https://www.eurekaselect.comarticle/107098 <![CDATA[Potential Prognostic Predictors and Molecular Targets for Skin Melanoma Screened by Weighted Gene Co-expression Network Analysis]]>https://www.eurekaselect.comarticle/106684Aims and Objectives: Among skin cancers, malignant skin melanoma is the leading cause of death. Identification of gene markers of malignant skin melanoma associated with survival may provide new clues for prognosis prediction and treatment. This research aimed to screen out potential prognostic predictors and molecular targets for malignant skin melanoma.

Introduction: Information regarding gene expression in skin melanoma and patients’ clinical traits was obtained from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA) was applied to build co-expression modules and investigate the association between the modules and clinical traits. Moreover, functional enrichment analysis was performed for clinically significant co-expression modules. Hub genes of these modules were validated via Gene Expression Profiling Interactive Analysis (GEPIA) and the Human Protein Atlas (http:// www.proteinatlas.org).

Methods: First, using WGCNA, 9 co-expression modules were constructed by the top 25% differentially expressed genes (4406 genes) from 77 human melanoma samples. Two co-expression modules (magenta and blue modules) were significantly correlated with survival months (r = -0.27, p = 0.02; r = 0.27, p = 0.02, respectively). The results of functional enrichment analysis demonstrated that the magenta module was mainly enriched in the cell cycle process and the blue module was mainly enriched in the immune response process. Additionally, the GEPIA and Human Protein Atlas results suggested that the hub genes CCNB2, ARHGAP30, and SEMA4D were associated with relapse-free survival and overall survival (all p-values < 0.05) and were differentially expressed in melanoma tumors and normal skin.

Results and Conclusion: The results provided the framework of co-expression gene modules of skin melanoma and screened out CCNB2, ARHGAP30, and SEMA4D associated with survival as potential prognostic predictors and molecular targets of treatment.

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<![CDATA[Treatment of Psoriasis: A Comprehensive Review of Entire Therapies]]>https://www.eurekaselect.comarticle/103958Background: Psoriasis is an autoimmune disease that ingeminates itself with the repeated proliferation of keratinocytes. It globally strikes a 2-5 % population on an average. Management of psoriasis remains a daunting task with various challenges influencing treatment, such as patient conformity and adherence to therapy, delicate patient profiles, psychological aspects, and skin as a barrier to topical delivery. The first part reviewed pathophysiology, triggering factors, and clinical classification. The second part reviewed all the therapies, such as topical, oral, biological, parenteral therapy, phototherapy, and the phyto-pharmaceuticals.

Methods: The research data related to the existing and upcoming therapies for psoriasis treatment, several nanocarriers, existing marketed formulations, and detailed description of phytopharmaceuticals with their mechanism.

Results: Topical therapy is the mainstay treatment option with limited adverse effects. Biological therapy has reformed conventional psoriasis treatment by being more efficacious and has increased patient acceptance due to decreased adverse events. Nanoformulations present an edge over conventional therapy due to improved anti-psoriatic effect and decreased side effects. Phyto-pharmaceuticals act as a complementary and alternative therapy for diminishing psoriasis symptoms.

Conclusion: A rationalized cost-effective patient compliant therapy is required for effective management and complete cure of psoriasis.

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<![CDATA[Biological Activities of Flavonoids from the Wood Extract of Artocarpus heterophyllus L. (Jackfruit)]]>https://www.eurekaselect.comarticle/93803Background: Artocarpus heterophyllus L. (Jackfruit) has been used traditionally as treatment for inflammation and cancer. The aim of this study was to isolate compounds from A. heterophyllus wood extract and evaluate their biological activities such as anti-tumor promoting effect on Epstein-Barr virus early antigen induction, melanogenesis inhibitory activity on the B16 mouse melanoma 4A5 cell line and cytotoxic activity against three human cancer cell lines (HL60, A549, SK-BR-3).

Methods: A. heterophyllus wood was extracted with n-hexane and methanol. The ethyl acetate soluble- fraction separated from the methanol extract was separated and purified with column chromatography to isolate compounds. The structures of isolated compounds were elucidated with spectroscopic methods. These compounds were evaluated for their biological activities.

Results: Thirteen known compounds including four prenylflavonoids were isolated from the wood extracts. Nine flavonoids (2, 3, 5-11) exhibited potent anti-tumor promoting activity with IC50 values of 259-296 molar ratio / 32 pmol TPA. Two flavonoids, Norartocarpetin (6) at concentration of 30 μM and cyanomaclurin (11) at the concentration of 100 μM showed melanin content value of 47.6 % and 80.1 %, respectively. Two prenylflavonoids, cudraflavone B (2) and artocarpin (5), showed cytotoxicity against the human cancer cell lines tested. Cudraflavone B (2) showed cytotoxicity against all three human cancer cell lines whereas artocarpin (5) only exhibited cytotoxicity against two out three cell lines testes. The IC50 values were comparable to or better than cisplatin.

Conclusion: From the view point of structure activity relationships of the flavonoids isolated, side chains such as prenyl and 3-methyl-1-butenyl moiety were key for their potent biological activities.

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<![CDATA[Lactic Acid Bacteria and Lactic Acid for Skin Health and Melanogenesis Inhibition]]>https://www.eurekaselect.comarticle/103574 <![CDATA[Live Impedance Measurements and Time-lapse Microscopy Observations of Cellular Adhesion, Proliferation and Migration after Ionizing Radiation]]>https://www.eurekaselect.comarticle/103199Background: Changes in the cellular behavior depend on environmental and intracellular interactions. Cancer treatments force the changes, first on the molecular level, but the main visible changes are macroscopic. During radiotherapy, cancer cell’s adhesion, proliferation and migration should be well monitored. In over 60% of diagnosed cancers cases, patients are given treatments with different protocols of radiotherapy, which result in possible metastasis and acute whole body response to toxic radiation.

Objective: Effectiveness of the therapy used depends on the sensitivity/resistance of irradiated cancer cells. Cellular mechanisms of cancer protection, such as the activation of DNA damage and repair pathways, antioxidants production and oxidative stress suppression during treatments are not desirable. Cancer cells monitoring require the development of novel techniques, and the best techniques are non-invasive and long-term live observation methods, which are shown in this study.

Methods: In cancers, invasive and metastatic phenotypes could be enhanced by stimulation of proliferation rate, decreased adhesion with simultaneous increase of motility and migration potential. For such reasons, the Ionizing Radiation (IR) stimulated proliferation; migration with lowered adhesiveness of cancer Me45 and normal fibroblasts NHDF were studied. Using impedance measurements technique for live cells, the adhesion of cells after IR exposition was assessed. Additionally proliferation and migration potential, based on standard Wound Healing assay were evaluated by timelapse microscopic observations.

Results: We found simulative IR dose-ranges (0.2-2 Gy) for Me45 and NHDF cells, with higher proliferation and adhesion rates. On the other hand, lethal impact of IR (10-12 Gy) on both the cell lines was indicated.

Conclusion: Over-confluence cell populations, characterized with high crowd and contact inhibition could modulate invasiveness of individual cells, convert them to display migration phenotype and advance motility, especially after radiotherapy treatments.

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<![CDATA[Molecular Identification of Phytochemical for Anticancer Treatment]]>https://www.eurekaselect.comarticle/104473 <![CDATA[Pisosterol Induces G2/M Cell Cycle Arrest and Apoptosis via the ATM/ATR Signaling Pathway in Human Glioma Cells]]>https://www.eurekaselect.comarticle/104190Background: Pisosterol, a triterpene derived from Pisolithus tinctorius, exhibits potential antitumor activity in various malignancies. However, the molecular mechanisms that mediate the pisosterol-specific effects on glioma cells remain unknown.

Objective: This study aimed to evaluate the antitumoral effects of pisosterol on glioma cell lines.

Methods: The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and trypan blue exclusion assays were used to evaluate the effect of pisosterol on cell proliferation and viability in glioma cells. The effect of pisosterol on the distribution of the cells in the cell cycle was performed by flow cytometry. The expression and methylation pattern of the promoter region of MYC, ATM, BCL2, BMI1, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, MDM2, p14ARF and TP53 was analyzed by RT-qPCR, western blotting and bisulfite sequencing PCR (BSP-PCR).

Results: Here, it has been reported that pisosterol markedly induced G2/M arrest and apoptosis and decreased the cell viability and proliferation potential of glioma cells in a dose-dependent manner by increasing the expression of ATM, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, p14ARF and TP53 and decreasing the expression of MYC, BCL2, BMI1 and MDM2. Pisosterol also triggered both caspase-independent and caspase-dependent apoptotic pathways by regulating the expression of Bcl-2 and activating caspase-3 and p53.

Conclusion: It has been, for the first time, confirmed that the ATM/ATR signaling pathway is a critical mechanism for G2/M arrest in pisosterol-induced glioma cell cycle arrest and suggests that this compound might be a promising anticancer candidate for further investigation.

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<![CDATA[The Effect of Phase Transition Temperature on Therapeutic Efficacy of Liposomal Bortezomib]]>https://www.eurekaselect.comarticle/103385Aims: Here, three liposomal formulations of DPPC/DPPG/Chol/DSPE-mPEG2000 (F1), DPPC/DPPG/Chol (F2) and HSPC/DPPG/Chol/DSPE-mPEG2000 (F3) encapsulating BTZ were prepared and characterized in terms of their size, surface charge, drug loading, and release profile. Mannitol was used as a trapping agent to entrap the BTZ inside the liposomal core. The cytotoxicity and anti-tumor activity of formulations were investigated in vitro and in vivo in mice bearing tumor.

Background: Bortezomib (BTZ) is an FDA approved proteasome inhibitor for the treatment of mantle cell lymphoma and multiple myeloma. The low solubility of BTZ has been responsible for the several side effects and low therapeutic efficacy of the drug. Encapsulating BTZ in a nano drug delivery system; helps overcome such issues. Among NDDSs, liposomes are promising diagnostic and therapeutic delivery vehicles in cancer treatment.

Objective: Evaluating anti-tumor activity of bortezomib liposomal formulations.

Methods: Data prompted us to design and develop three different liposomal formulations of BTZ based on Tm parameter, which determines liposomal stiffness. DPPC (Tm 41°C) and HSPC (Tm 55°C) lipids were chosen as variables associated with liposome rigidity. In vitro cytotoxicity assay was then carried out for the three designed liposomal formulations on C26 and B16F0, which are the colon and melanoma cancer mouse-cell lines, respectively. NIH 3T3 mouse embryonic fibroblast cell line was also used as a normal cell line. The therapeutic efficacy of these formulations was further assessed in mice tumor models.

Result: MBTZ were successfully encapsulated into all the three liposomal formulations with a high entrapment efficacy of 60, 64, and 84% for F1, F2, and F3, respectively. The findings showed that liposomes mean particle diameter ranged from 103.4 to 146.8nm. In vitro cytotoxicity studies showed that liposomal-BTZ formulations had higher IC50 value in comparison to free BTZ. F2-liposomes with DPPC, having lower Tm of 41°C, showed much higher anti-tumor efficacy in mice models of C26 and B16F0 tumors compared to F3-HSPC liposomes with a Tm of 55°C. F2 formulation also enhanced mice survival compared with untreated groups, either in BALB/c or in C57BL/6 mice.

Conclusion: Our findings indicated that F2-DPPC-liposomal formulations prepared with Tm close to body temperature seem to be effective in reducing the side effects and increasing the therapeutic efficacy of BTZ and merits further investigation.

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<![CDATA[Relevance of Molecular Docking Studies in Drug Designing]]>https://www.eurekaselect.comarticle/103082 <![CDATA[Melanoma: Prognostic Factors and Factors Predictive of Response to Therapy]]>https://www.eurekaselect.comarticle/102797Background: A better understanding of prognostic factors and biomarkers that predict response to treatment is required in order to further improve survival rates in patients with melanoma.

Prognostic Factors: The most important histopathological factors prognostic of worse outcomes in melanoma are sentinel lymph node involvement, increased tumor thickness, ulceration and higher mitotic rate. Poorer survival may also be related to several clinical factors, including male gender, older age, axial location of the melanoma, elevated serum levels of lactate dehydrogenase and S100B.

Predictive Biomarkers: Several biomarkers have been investigated as being predictive of response to melanoma therapies. For anti-Programmed Death-1(PD-1)/Programmed Death-Ligand 1 (PD-L1) checkpoint inhibitors, PD-L1 tumor expression was initially proposed to have a predictive role in response to anti-PD-1/PD-L1 treatment. However, patients without PD-L1 expression also have a survival benefit with anti-PD-1/PD-L1 therapy, meaning it cannot be used alone to select patients for treatment, in order to affirm that it could be considered a correlative, but not a predictive marker. A range of other factors have shown an association with treatment outcomes and offer potential as predictive biomarkers for immunotherapy, including immune infiltration, chemokine signatures, and tumor mutational load. However, none of these have been clinically validated as a factor for patient selection. For combined targeted therapy (BRAF and MEK inhibition), lactate dehydrogenase level and tumor burden seem to have a role in patient outcomes.

Conclusion: With increasing knowledge, the understanding of melanoma stage-specific prognostic features should further improve. Moreover, ongoing trials should provide increasing evidence on the best use of biomarkers to help select the most appropriate patients for tailored treatment with immunotherapies and targeted therapies.

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<![CDATA[A Review of IGF1 Signaling and IGF1-related Long Noncoding RNAs in Chemoresistance of Cancer]]>https://www.eurekaselect.comarticle/104917 <![CDATA[Idronoxil as an Anticancer Agent: Activity and Mechanisms]]>https://www.eurekaselect.comarticle/103419 <![CDATA[Lipids as Activators of Innate Immunity in Peptide Vaccine Delivery]]>https://www.eurekaselect.comarticle/94014Background: Innate immune system plays an important role in pathogen detection and the recognition of vaccines, mainly through pattern recognition receptors (PRRs) that identify pathogen components (danger signals). One of the typically recognised bacterial components are lipids in conjugation with peptides, proteins and saccharides. Lipidic compounds are readily recognised by the immune system, and thus are ideal candidates for peptide- based vaccine delivery. Thus, bacterial or synthetic lipids mixed with, or conjugated to, antigens have shown adjuvant properties. These systems have many advantages over traditional adjuvants, including low toxicity and good efficacy for stimulating mucosal and systemic immune responses.

Methods: The most recent literature on the role of lipids in stimulation of immune responses was selected for this review. The vast majority of reviewed papers were published in the last decade. Older but significant findings are also cited.

Results: This review focuses on the development of lipopeptide vaccine systems including application of palmitic acid, bacterial lipopeptides, glycolipids and the lipid core peptide and their routes of administration. The use of liposomes as a delivery system that incorporates lipopeptides is discussed. The review also includes a brief description of immune system in relation to vaccinology and discussion on vaccine delivery routes.

Conclusion: Lipids and their conjugates are an ideal frontrunner in the development of safe and efficient vaccines for different immunisation routes.

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<![CDATA[Metastatic Colorectal Cancer: Prognostic and Predictive Factors]]>https://www.eurekaselect.comarticle/99092Colorectal cancer represents the third most frequently occurring cancer worldwide. In the last decade, the survival of patients affected by metastatic colorectal cancer (mCRC) has improved through the introduction of biological drugs. However, in this new and dynamic therapeutic context, research about prognostic and predictive factors is important to guide the oncologists to effective therapies as well as to improve the understanding of colorectal cancer biology. Their identification is an intensive area of research and our future goal will be to depict tumour-specific "molecular signatures" in order to predict the clinical course of the disease and the best treatments.

In this report, we describe clinical, pathological and molecular biomarkers that can play a role as prognostic or predictive factors in mCRC.

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<![CDATA[CDK9: Therapeutic Perspective in HCC Therapy]]>https://www.eurekaselect.comarticle/104445 <![CDATA[T-type Calcium Channels in Health and Disease]]>https://www.eurekaselect.comarticle/93312 <![CDATA[Targeted Radionuclide Therapy of Painful Bone Metastases: Past Developments, Current Status, Recent Advances and Future Directions]]>https://www.eurekaselect.comarticle/96301 <![CDATA[Natural-based Hydrogels: A Journey from Simple to Smart Networks for Medical Examination]]>https://www.eurekaselect.comarticle/100278 <![CDATA[Use of Anticancer Platinum Compounds in Combination Therapies and Challenges in Drug Delivery]]>https://www.eurekaselect.comarticle/94271 <![CDATA[Natural Products Containing Olefinic Bond: Important Substrates for Semi-synthetic Modification Towards Value Addition]]>https://www.eurekaselect.comarticle/105183 <![CDATA[Manipulation of the Immune System for Cancer Defeat: A Focus on the T Cell Inhibitory Checkpoint Molecules]]>https://www.eurekaselect.comarticle/94306 <![CDATA[Therapeutic Potential of Medicinal Plant Proteins: Present Status and Future Perspectives]]>https://www.eurekaselect.comarticle/102449 <![CDATA[Isoform-Selective PI3K Inhibitors for Various Diseases]]>https://www.eurekaselect.comarticle/103500 <![CDATA[Knockdown of Enhancer of Zeste Homolog 2 Affects mRNA Expression of Genes Involved in the Induction of Resistance to Apoptosis in MOLT-4 Cells]]>https://www.eurekaselect.comarticle/104079Background: The Enhancer of Zeste Homolog 2 (EZH2) is a subunit of the polycomb repressive complex 2 that silences the gene transcription via H3K27me3. Previous studies have shown that EZH2 has an important role in the induction of the resistance against the Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL)-Induced Apoptosis (TIA) in some leukemia cells.

Objective: The aim of this study was to determine the effect of silencing EZH2 gene expression using RNA interference on the expression of death receptors 4 and 5 (DR4/5), Preferentially expressed Antigen in Melanoma (PRAME), and TRAIL human lymphoid leukemia MOLT-4 cells.

Methods: Quantitative RT-PCR was used to detect the EZH2 expression and other candidate genes following the siRNA knockdown in MOLT-4 cells. The toxicity of the EZH2 siRNA was evaluated using Annexin V/PI assay following the transfection of the cells by 80 pM EZH2 siRNA at 48 hours.

Results: Based on the flow-cytometry results, the EZH2 siRNA had no toxic effects on MOLT-4 cells. Also, the EZH2 inhibition increased the expression of DR4/5 but reduced the PRAME gene expression at the mRNA levels. Moreover, the EZH2 silencing could not change the TRAIL mRNA in the transfected cells.

Conclusion: Our results revealed that the down-regulation of EZH2 in MOLT-4 cells was able to affect the expression of important genes involved in the induction of resistance against TIA. Hence, we suggest that the silencing of EZH2 using RNA interference can be an effective and safe approach to help defeat the MOLT-4 cell resistance against TIA.

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<![CDATA[Insights into Nano-Photo-Thermal Therapy of Cancer: The Kinetics of Cell Death and Effect on Cell Cycle]]>https://www.eurekaselect.comarticle/104024Background: Despite considerable advances in nano-photo-thermal therapy (NPTT), there have been a few studies reporting in-depth kinetics of cell death triggered by such a new modality of cancer treatment.

Objective: In this study, we aimed to (1) investigate the cell death pathways regulating the apoptotic responses to NPTT; and (2) ascertain the effect of NPTT on cell cycle progression.

Methods: Folate conjugated gold nanoparticle (F-AuNP) was firstly synthesized, characterized and then assessed to determine its potentials in targeted NPTT. The experiments were conducted on KB nasopharyngeal cancer cells overexpressing folate receptors (FRs), as the model, and L929 normal fibroblast cells with a low level of FRs, as the control. Cytotoxicity was evaluated by MTT assay and the cell death mode (i.e., necrosis or apoptosis) was determined through AnnexinV/FITC-propidium iodide staining. Next, the gene expression profiles of some key apoptotic factors involved in the mitochondrial signaling pathway were investigated using RT-qPCR. Finally, cell cycle phase distribution was investigated at different time points post NPTT using flow cytometric analysis.

Results: The obtained results showed that KB cell death following targeted NPTT was greater than that observed for L929 cells. The majority of KB cell death following NPTT was related to apoptosis. RT-qPCR analysis indicated that the elevated expression of Bax along with the depressed expression of Bcl-xL, Survivin and XIAP may involve in the regulation of apoptosis in response to NPTT. Flow cytometric analysis manifested that 16-24 hours after NPTT, the major proportion of KB cells was in the most radiosensitive phases of the cell cycle (G2/M).

Conclusion: This study extended the understanding of the signaling pathway involved in the apoptotic response to NPTT. Moreover, the potential effect of NPTT on sensitizing cancer cells to subsequent radiation therapy was highlighted.

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<![CDATA[Deep Learning Approaches Towards Skin Lesion Segmentation and Classification from Dermoscopic Images - A Review]]>https://www.eurekaselect.comarticle/96187Background: Automated intelligent systems for unbiased diagnosis are primary requirement for the pigment lesion analysis. It has gained the attention of researchers in the last few decades. These systems involve multiple phases such as pre-processing, feature extraction, segmentation, classification and post processing. It is crucial to accurately localize and segment the skin lesion. It is observed that recent enhancements in machine learning algorithms and dermoscopic techniques reduced the misclassification rate therefore, the focus towards computer aided systems increased exponentially in recent years. Computer aided diagnostic systems are reliable source for dermatologists to analyze the type of cancer, but it is widely acknowledged that even higher accuracy is needed for computer aided diagnostic systems to be adopted practically in the diagnostic process of life threatening diseases.

Introduction: Skin cancer is one of the most threatening cancers. It occurs by the abnormal multiplication of cells. The core three types of skin cells are: Squamous, Basal and Melanocytes. There are two wide classes of skin cancer; Melanocytic and non-Melanocytic. It is difficult to differentiate between benign and malignant melanoma, therefore dermatologists sometimes misclassify the benign and malignant melanoma. Melanoma is estimated as 19th most frequent cancer, it is riskier than the Basel and Squamous carcinoma because it rapidly spreads throughout the body. Hence, to lower the death risk, it is critical to diagnose the correct type of cancer in early rudimentary phases. It can occur on any part of body, but it has higher probability to occur on chest, back and legs.

Methods: The paper presents a review of segmentation and classification techniques for skin lesion detection. Dermoscopy and its features are discussed briefly. After that Image pre-processing techniques are described. A thorough review of segmentation and classification phases of skin lesion detection using deep learning techniques is presented Literature is discussed and a comparative analysis of discussed methods is presented.

Conclusion: In this paper, we have presented the survey of more than 100 papers and comparative analysis of state of the art techniques, model and methodologies. Malignant melanoma is one of the most threating and deadliest cancers. Since the last few decades, researchers are putting extra attention and effort in accurate diagnosis of melanoma. The main challenges of dermoscopic skin lesion images are: low contrasts, multiple lesions, irregular and fuzzy borders, blood vessels, regression, hairs, bubbles, variegated coloring and other kinds of distortions. The lack of large training dataset makes these problems even more challenging. Due to recent advancement in the paradigm of deep learning, and specially the outstanding performance in medical imaging, it has become important to review the deep learning algorithms performance in skin lesion segmentation. Here, we have discussed the results of different techniques on the basis of different evaluation parameters such as Jaccard coefficient, sensitivity, specificity and accuracy. And the paper listed down the major achievements in this domain with the detailed discussion of the techniques. In future, it is expected to improve results by utilizing the capabilities of deep learning frameworks with other pre and post processing techniques so reliable and accurate diagnostic systems can be built.

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<![CDATA[Ultrasonic Echolocation Device for Assisting the Visually Impaired]]>https://www.eurekaselect.comarticle/98207Background: Echolocation is a technique whereby the location of objects is determined via reflected sound. Currently, some visually impaired individuals use a form of echolocation to locate objects and to orient themselves. However, this method takes years of practice to accurately utilize.

Aims: This paper presents the development of a sensory substitution device for visually impaired users, which gauged distances and the placement of objects.

Methods: Using ultrasonic technology, the device employed a method of echolocation to increase the user's independence and mobility. The main components of this device are an ultrasound transceiver and a miniaturized Arduino board. Through research and prototyping, this technology was integrated into a biomedical application in a watch form factor which provides feedback to the user regarding the measured distance by the ultrasonic transducer.

Results: The output of this process is a tactile feedback that varies in intensity proportional to the distance of the detected object. We tested the device in different scenarios including different distances from a different material. The difference between the device reading and the actual distance, from 0 to 400 cm was statistically insignificant.

Conclusion: It is believed this device will boost the confidence of the user in navigation.

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<![CDATA[Breast Infrared Thermography Segmentation Based on Adaptive Tuning of a Fully Convolutional Network]]>https://www.eurekaselect.comarticle/98354Background: Accurate segmentation of Breast Infrared Thermography is an important step for early detection of breast pathological changes. Automatic segmentation of Breast Infrared Thermography is a very challenging task, as it is difficult to find an accurate breast contour and extract regions of interest from it. Although several semi-automatic methods have been proposed for segmentation, their performance often depends on hand-crafted image features, as well as preprocessing operations.

Objectives: In this work, an approach to automatic semantic segmentation of the Breast Infrared Thermography is proposed based on end-to-end fully convolutional neural networks and without any pre or post-processing.

Methods: The lack of labeled Breast Infrared Thermography data limits the complete utilization of fully convolutional neural networks. The proposed model overcomes this challenge by applying data augmentation and two-tier transfer learning from bigger datasets combined with adaptive multi-tier fine-tuning before training the fully convolutional neural networks model.

Results: Experimental results show that the proposed approach achieves better segmentation results: 97.986% accuracy; 98.36% sensitivity and 97.61% specificity compared to hand-crafted segmentation methods.

Conclusion: This work provided an end-to-end automatic semantic segmentation of Breast Infrared Thermography combined with fully convolutional networks, adaptive multi-tier fine-tuning and transfer learning. Also, this work was able to deal with challenges in applying convolutional neural networks on such data and achieving the state-of-the-art accuracy.

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<![CDATA[Ligand Based Pharmacophore Modeling Followed by Biological Screening Lead to Discovery of Novel PDK1 Inhibitors as Anticancer Agents]]>https://www.eurekaselect.comarticle/103187Background: Phosphoinositide-Dependent Kinase-1 (PDK1) is a serine/threonine kinase, which belongs to AGC kinase family required by cancer cells.

Methods: Pharmacophoric space of 86 PDK1 inhibitors using six diverse sets of inhibitors was explored to identify high-quality pharmacophores. The best combination of pharmacophoric models and physicochemical descriptors was selected by genetic algorithm-based QSAR analysis that can elucidate the variation of bioactivity within the training inhibitors. Two successful orthogonal pharmacophores emerged in the optimum QSAR equation (r2 69 = 0.90, r2 LOO= 0.86, F= 51.92, r2 PRESS against 17 test inhibitors = 0.79). Receiver Operating Characteristic (ROC) curve analyses were used to estimate the QSAR-selected pharmacophores.

Results: 5 out of 11 compounds tested had shown potential intracellular PDK1 inhibition with the highest inhibition percent for compounds 92 and 93 as follows; 90 and 92% PDK1 inhibition, respectively.

Conclusion: PDK1 inhibitors are potential anticancer agents that can be discovered by combination method of ligand based design with QSAR and ROC analysis.

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