<![CDATA[Mesothelioma]]> https://benthamscience.com RSS Feed for Disease Wise Article | BenthamScience EurekaSelect (+http://eurekaselect.com) Thu, 28 Mar 2024 22:03:44 +0000 <![CDATA[Mesothelioma]]> https://benthamscience.com https://benthamscience.com <![CDATA[Rediscovering Tocophersolan: A Renaissance for Nano-Based Drug Delivery and Nanotheranostic Applications]]>https://benthamscience.comarticle/107279 <![CDATA[Comprehensive Analysis Reveals GPRIN1 is a Potential Biomarker for Non-sm all Cell Lung Cancer]]>https://benthamscience.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[Anticancer Properties of Amino Acid and Peptide Derivatives of Mycophenolic Acid]]>https://benthamscience.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[An <i>In vivo</i> Immunohistochemical Study on MacroH2A.1 in Lung and Lymph-Node Tissues Exposed to an Asbestiform Fiber]]>https://benthamscience.comarticle/104697 Background: The correlation between asbestiform fibers, lung cancer, pleural mesothelioma, and other lung diseases is already well established as the pathophisiological pathophysiological respiratory mechanisms involved by inhalation of Fluoro-edenite (FE). The latter is represented by cell proliferation and inducing the release of growth factors, cytokines, and reactive oxygen and nitrite species, with DNA damage that causes chronic inflammation and carcinogenesis. MacroH2A.1, and histone variant, seems to play a role in sensing the metabolic state of the cell and linking it with chromatin. Physiologically, MacroH2A.1 is expressed at low levels in stem cells and it became upregulated during differentiation, preventing reprogramming of induced pluripotent stem cells and after nuclear transfer. In particular, MacroH2A.1 has been shown to explicate a potent antitumor mechanism in vivo as it results upregulated in senescent cells determining a permanent growth-arrest.

Objective: Evaluate the possible role of the histone variant in the organism in response to deep insight understanding the mechanisms of toxicity and the cellular response to FE.

Methods: Lung and lymph nodes of exposed sheep were selected. Samples were processed for histological and immunihistochemical immunohistochemical evaluations. Densitometric, morphometric, and statistical analysis analyses were conducted.

Results: Tissue sections of FE exposed sheep demonstrated overexpression of MacroH2A.1 vs unexposed samples. The data suggest an involvement of these this molecule in the cellular response triggered by FE directed exposure.

Conclusion: In this contest, MacroH2A.1 overexpression supports its function as an epigenetic stabilizer that helps to establish and maintain differentiated states.]]>
<![CDATA[Anti-Tumor Effects of Osthole on Different Malignant Tissues: A Review of Molecular Mechanisms]]>https://benthamscience.comarticle/104902 <![CDATA[Development of Pin1 Inhibitors and their Potential as Therapeutic Agents]]>https://benthamscience.comarticle/94272The prolyl isomerase Pin1 is a unique enzyme, which isomerizes the cis-trans conformation between pSer/pThr and proline and thereby regulates the function, stability and/or subcellular distribution of its target proteins. Such regulations by Pin1 are involved in numerous physiological functions as well as the pathogenic mechanisms underlying various diseases. Notably, Pin1 deficiency or inactivation is a potential cause of Alzheimer’s disease, since Pin1 induces the degradation of Tau. In contrast, Pin1 overexpression is highly correlated with the degree of malignancy of cancers, as Pin1 controls a number of oncogenes and tumor suppressors. Accordingly, Pin1 inhibitors as anti-cancer drugs have been developed. Interestingly, recent intensive studies have demonstrated Pin1 to be responsible for the onset or development of nonalcoholic steatosis, obesity, atherosclerosis, lung fibrosis, heart failure and so on, all of which have been experimentally induced in Pin1 deficient mice.

In this review, we discuss the possible applications of Pin1 inhibitors to a variety of diseases including malignant tumors and also introduce the recent advances in Pin1 inhibitor research, which have been reported.

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<![CDATA[Idronoxil as an Anticancer Agent: Activity and Mechanisms]]>https://benthamscience.comarticle/103419 <![CDATA[Use of Anticancer Platinum Compounds in Combination Therapies and Challenges in Drug Delivery]]>https://benthamscience.comarticle/94271 <![CDATA[Manipulation of the Immune System for Cancer Defeat: A Focus on the T Cell Inhibitory Checkpoint Molecules]]>https://benthamscience.comarticle/94306 <![CDATA[In Silico Transcriptomic Analysis of the Chloride Intracellular Channels (CLIC) Interactome Identifies a Molecular Panel of Seven Prognostic Markers in Patients with Pancreatic Ductal Adenocarcinoma]]>https://benthamscience.comarticle/105253Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. In this context, the identification of biomarkers regarding the PDAC diagnosis, monitoring, and prognosis is crucial.

Objectives: The purpose of the current study was to investigate the differential gene expression profile of the chloride intracellular channel (CLIC) gene family network in patients with PDAC, in order to suggest novel biomarkers.

Methods: In silico techniques were used to construct the interactome of the CLIC gene family, identify the differentially expressed genes (DEGs) in PDAC as compared to healthy controls, and evaluate their potential prognostic role.

Results: Transcriptomic data of three microarray datasets were included, incorporating 114 tumor and 59 normal pancreatic samples. Twenty DEGs were identified; eight were up-regulated and twelve were downregulated. A molecular signature of seven genes (Chloride Intracellular Channel 1 – CLIC1; Chloride Intracellular Channel 3 – CLIC3; Chloride Intracellular Channel 4 – CLIC4; Ganglioside Induced Differentiation Associated Protein 1 – GDAP1; Ganglioside Induced Differentiation Associated Protein 1 Like 1 – GDAP1L1; Glutathione S-Transferase Pi 1 - GSTP1; Prostaglandin E Synthase 2 – PTGES2) were identified as prognostic markers associated with overall survival. Positive correlations were reported regarding the expression of CLIC1-CLIC3, CLIC4-CLIC5, and CLIC5- CLIC6. Finally, gene set enrichment analysis demonstrated the molecular functions and miRNA families (hsa-miR-122, hsa-miR-618, hsa-miR-425, and hsa-miR-518) relevant to the seven prognostic markers.

Conclusion: These outcomes demonstrate a seven-gene molecular panel that predicts the patients’ prospective survival following pancreatic resection for PDAC.

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<![CDATA[Ultrasound Characteristics in Complicated Ovarian Cysts]]>https://benthamscience.comarticle/103228

Objective: This work aims to study ultrasound characteristics of complicated ovarian cysts and their contribution to emergency department management.

Methods: It is a retrospective study of 61 patients who have consulted the emergency department, during 6 months, from November 2016 to April 2017. We included all patients consulting the emergency department for symptoms related to an ovarian cyst.

Results: The average size of the cysts was 5.38± 2.27 cm long axis, ranging from 3 to 12 cm. Their wall was thin in 59 cases and thick in 4 cases. They were unilocular in 82% and multilocular in 17.5% of cases. The echogenicity of the cysts varied. The contour of the cysts was regular in 54 cases, while irregularity was shown in 9 cases. Intracystic vegetations were illustrated in 4 cases. The solid component was demonstrated in only 1 cyst. The Douglas effusion was shown in 12.7% of cases.

The comparison of ultrasound findings between outpatient and hospitalized ones shows that there is no significant relationship between the following ultrasound features of ovarian cysts and hospitalization‘ s indication (p>5%).

Conclusion: Pelvic ultrasound is of great benefit in the diagnosis of ovarian cysts, however, there is no significant relationship between the features of ovarian cysts and indication of hospitalization (p>5%).]]>
<![CDATA[Circulating Biomarkers for Tumor Angiogenesis: Where Are We?]]>https://benthamscience.comarticle/92573

Objectives: The purpose of this review is to describe current reports on circulating diagnostic and prognostic biomarkers related to angiogenesis. We further discuss how this non-invasive strategy could improve the monitoring of tumor treatment and help clinical strategy.

Results: We discuss the latest evidence in the literature regarding circulating anti-angiogenic markers. Besides growth factor proteins, different circulating miRNAs could exert a pro- or anti-angiogenic activity so as to represent suitable candidates for a non-invasive strategy. Recent reports indicate that tumor-derived exosomes, which are small membrane vesicles abundant in biological fluids, also have an impact on vascular remodeling.

Conclusion: Numerous circulating biomarkers related to angiogenesis have been recently identified. Their use will allow identifying patients who are more likely to benefit from a specific anti-angiogenic treatment, as well as detecting those who will develop resistance and/or adverse effects. Nonetheless, further studies are required to elucidate the role of these biomarkers in clinical settings.]]>
<![CDATA[Design, Synthesis and In Vitro Anti-Cancer Evaluation of Novel Derivatives of 2-(2-Methyl-1,5-diaryl-1H-pyrrol-3-yl)-2-oxo-N-(pyridin-3- yl)acetamide]]>https://benthamscience.comarticle/98241Objective: Several anti-tubulin agents were introduced for the cancer treatment so far. Despite successes in the treatment of cancer, these agents cause toxic side effects, including peripheral neuropathy. Comparing anti-tubulin agents, indibulin seemed to cause minimal peripheral neuropathy, but its poor aqueous solubility and other potential clinical problems have led to its remaining in a preclinical stage.

Methods: Herein, indibulin analogues were synthesized and evaluated for their in vitro anti-cancer activity using MTT assay (on the MCF-7, T47-D, MDA-MB231 and NIH-3T3 cell lines), annexin V/PI staining assay, cell cycle analysis, anti-tubulin assay and caspase 3/7 activation assay.

Results: One of the compounds, 4a, showed good anti-proliferative activity against MCF-7 cells (IC50: 7.5 μM) and low toxicity on a normal cell line (IC50 > 100 μM). All of the tested compounds showed lower cytotoxicity on normal cell line in comparison to reference compound, indibulin. In the annexin V/PI staining assay, induction of apoptosis in the MCF-7 cell line was observed. Cell cycle analysis illustrated an increasing proportion of cells in the sub-G-1 phase, consistent with an increasing proportion of apoptotic cells. No increase in G2/M cells was observed, consistent with the absence of anti-tubulin activity. A caspase 3/7 assay protocol showed that apoptosis induction by more potent compounds was due to activation of caspase 3.

Conclusion: Newly synthesized compounds exerted acceptable anticancer activity and further investigation of current scaffold would be beneficial.

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<![CDATA[New Entrants into Clinical Trials for Targeted Therapy of Breast Cancer: An Insight]]>https://benthamscience.comarticle/101637 <![CDATA[Recent Advances in Characterizing Natural Products that Regulate Autophagy]]>https://benthamscience.comarticle/101454 <![CDATA[Gefitinib Represses JAK-STAT Signaling Activated by CRTC1-MAML2 Fusion in Mucoepidermoid Carcinoma Cells]]>https://benthamscience.comarticle/95575Background: Gefitinib is well-known as a tyrosine kinase inhibitor targeting non-smalllung- cancer (NSCLC) containing EGFR mutations. However, its effectiveness in treating mucoepidermoid carcinoma (MEC) without such EGFR mutations suggests additional targets.

Objective: The CRTC1-MAML2 (C1-M2) fusion typical for MEC has been proposed to be a gefitinib target.

Methods: To test this hypothesis, we developed a set of siRNAs to down-regulate C1-M2 expression. RNA-seq and Western blot techniques were applied to analyze the effects of gefitinib and siC1-M2 on the transcriptome of and the phosphorylation of tyrosine kinases in a MEC cell line H292.

Results: Deep-sequencing transcriptome analysis revealed that gefitinib extensively inhibited transcription of genes in JAK-STAT and MAPK/ERK pathways. Both siC1-M2 and gefitinib inhibited the phosphorylation of multiple signaling kinases in these signaling pathways, indicating that gefitinib inhibited JAK-STAT and MAPK/ERK pathways activated by C1-M2 fusion. Moreover, gefitinib inhibition of EGFR and MAPK/ERK was more effective than that of AKT, JAK2 and STATs, and their dependence on C1-M2 could be uncoupled. Taken together, our results suggest that gefitinib simultaneously represses phosphorylation of multiple key signaling proteins which are activated in MEC, in part by C1-M2 fusion. Gefitinib-repressed kinase phosphorylation explains the transcriptional repression of genes in JAK-STAT and MAPK/ERK pathways.

Conclusion: These findings provide new insights into the efficacy of gefitinib in treating mucoepidermoid carcinoma, and suggest that a combination of gefitinib and other inhibitors specifically against C1-M2 fusion could be more effective.

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<![CDATA[Non-invasive Biodiversified Sensors: A Modernized Screening Technology for Cancer]]>https://benthamscience.comarticle/101775Background: Biological sensors revolutionize the method of diagnoses of diseases from early to final stages using the biomarkers present in the body. Biosensors are advantageous due to the involvement of minimal sample collection with improved specificity and sensitivity for the detection of biomarkers.

Methods: Conventional biopsies restrict problems like patient non-compliance, cross-infection and high cost and to overcome these issues biological samples like saliva, sweat, urine, tears and sputum progress into clinical and diagnostic research for the development of non-invasive biosensors. This article covers various non-invasive measurements of biological samples, optical-based, mass-based, wearable and smartphone-based biosensors for the detection of cancer.

Results: The demand for non-invasive, rapid and economic analysis techniques escalated due to the modernization of the introduction of self-diagnostics and miniature forms of devices. Biosensors have high sensitivity and specificity for whole cells, microorganisms, enzymes, antibodies, and genetic materials.

Conclusion: Biosensors provide a reliable early diagnosis of cancer, which results in faster therapeutic outcomes with in-depth fundamental understanding of the disease progression.

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<![CDATA[Drug Repurposing Screen Identifies Novel Classes of Drugs with Anticancer Activity in Mantle Cell Lymphoma]]>https://benthamscience.comarticle/100815Aim and Objective: Mantle Cell Lymphoma (MCL) is typically an aggressive and rare disease with poor prognosis, therefore new effective therapeutics are urgently needed. Drug repurposing for cancer treatment is becoming increasingly more attractive as an alternative approach to discover clinically approved drugs that demonstrate antineoplastic effect. The objective of this study was to screen an approved drug library and identify candidate compounds with an antineoplastic effect in MCL cells using High-Throughput Screening (HTS) technique.

Materials and Methods: Using the HTS technique, nearly 3,800 clinically approved drugs and drug candidates were screened in Jeko and Mino MCL cell lines. We also demonstrated the selectivity window of the candidate compounds in six normal cell lines. Further validations were performed in caspase-3/7 apoptosis assay and three-dimensional (3D) multicellular aggregates model using Z138 cell line.

Results: We identified 98 compounds showing >50% inhibition in either MCL cell line screened, they were distributed across eight unique therapeutic categories and have different mechanisms of action (MOA). We selected alisertib, carfilzomib, pracinostat and YM155 for further validation based on their antiproliferative activity in two MCL cell lines, selectivity to normal cell lines, and drug developing stages in terms of clinical research. Alisertib and carfilzomib showed antiproliferative effect on MCL cell with EC50 = 6 nM and >100-fold selectivity to normal cell lines, especially for alisertib which demonstrated >1000-fold selectivity to 5 out of 6 normal cell lines. Pracinostat and YM155 had potency of 11 and 12 nM in MCL cell with >20-fold selectivity to normal cell lines. All four compounds had been tested in caspase-dependent apoptosis assay. We further validated and demonstrated their anti-MCL effect on cell proliferation and (3D) multicellular aggregates model using Z138 cell line.

Conclusion: This is the first study to examine such a large library of clinically approved compounds for the identification of novel drug candidates for MCL treatment, the results could be rapidly translated into clinical practice in patients with MCL.

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<![CDATA[STING Activation and its Application in Immuno-Oncology]]>https://benthamscience.comarticle/101339 <![CDATA[Circulating and Tissue microRNAs as Biomarkers for Ovarian Cancer Prognosis]]>https://benthamscience.comarticle/99448 <![CDATA[Intercellular Crosstalk Via Extracellular Vesicles in Tumor Milieu as Emerging Therapies for Cancer Progression ]]>https://benthamscience.comarticle/99324Increasing evidence has suggested that extracellular vesicles (EV) mediated bidirectional transfer of functional molecules (such as proteins, different types of RNA, and lipids) between cancer cells and tumor stromal cells (immune cells, endothelial cells, fibroblasts, stem cells) and strongly contributed to the reinforcement of cancer progression. Thus, intercellular EV-mediated signaling in tumor microenvironment (TME) is essential in the modulation of all processes that support and promote tumor development like immune suppression, angiogenesis, invasion and metastasis, and resistance of tumor cells to anticancer treatments.

Besides EV potential to revolutionize our understanding of the cancer cell-stromal cells crosstalk in TME, their ability to selectively transfer different cargos to recipient cells has created excitement in the field of tumortargeted delivery of specific molecules for anticancer treatments. Therefore, in tight connection with previous findings, this review brought insight into the dual role of EV in modulation of TME. Thus, on one side EV create a favorable phenotype of tumor stromal cells for tumor progression; however, as a future new class of anticancer drug delivery systems EV could re-educate the TME to overcome main supportive processes for malignancy progression.

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<![CDATA[Anti-tumor Drug Targets Analysis: Current Insight and Future Prospect ]]>https://benthamscience.comarticle/97752 <![CDATA[Lipid-Based Vectors for Therapeutic mRNA-Based Anti-Cancer Vaccines]]>https://benthamscience.comarticle/99066 <![CDATA[Acrylamide Induced Toxicity and the Propensity of Phytochemicals in Amelioration: A Review ]]>https://benthamscience.comarticle/96493 <![CDATA[New Promises to Cure Cancer and Other Genetic Diseases/Disorders: Epi-drugs Through Epigenetics]]>https://benthamscience.comarticle/98700 <![CDATA[Research Advances in the Use of Histone Deacetylase Inhibitors for Epigenetic Targeting of Cancer]]>https://benthamscience.comarticle/96117 <![CDATA[Analysis of Hypoxiamir-Gene Regulatory Network Identifies Critical MiRNAs Influencing Cell-Cycle Regulation Under Hypoxic Conditions]]>https://benthamscience.comarticle/96729Background: Hypoxia is a pathophysiological condition which arises due to low oxygen concentration in conditions like cardiovascular diseases, inflammation, ascent to higher altitude, malignancies, deep sea diving, prenatal birth, etc. A number of microRNAs (miRNAs), Transcription Factors (TFs) and genes have been studied separately for their role in hypoxic adaptation and controlling cell-cycle progression and apoptosis during this stress.

Objective: We hypothesize that miRNAs and TFs may act in conjunction to regulate a multitude of genes and play a crucial and combinatorial role during hypoxia-stress-responses and associated cellcycle control mechanisms.

Method: We collected a comprehensive and non-redundant list of human hypoxia-responsive miRNAs (also known as hypoxiamiRs). Their experimentally validated gene-targets were retrieved from various databases and a comprehensive hypoxiamiR-gene regulatory network was built.

Results: Functional characterization and pathway enrichment of genes identified phospho-proteins as enriched nodes. The phospho-proteins which were localized both in the nucleus and cytoplasm and could potentially play important role as signaling molecules were selected; and further pathway enrichment revealed that most of them were involved in NFkB signaling. Topological analysis identified several critical hypoxiamiRs and network perturbations confirmed their importance in the network. Feed Forward Loops (FFLs) were identified in the subnetwork of enriched genes, miRNAs and TFs. Statistically significant FFLs consisted of four miRNAs (hsa-miR-182-5p, hsa- miR-146b-5p, hsa-miR-96, hsa-miR-20a) and three TFs (SMAD4, FOXO1, HIF1A) both regulating two genes (NFkB1A and CDKN1A).

Conclusion: Detailed BioCarta pathway analysis identified that these miRNAs and TFs together play a critical and combinatorial role in regulating cell-cycle under hypoxia, by controlling mechanisms that activate cell-cycle checkpoint protein, CDKN1A. These modules work synergistically to regulate cell-proliferation, cell-growth, cell-differentiation and apoptosis during hypoxia. A detailed mechanistic molecular model of how these co-regulatory FFLs may regulate the cell-cycle transitions during hypoxic stress conditions is also put forth. These biomolecules may play a crucial and deterministic role in deciding the fate of the cell under hypoxic-stress.

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<![CDATA[Novel Tri-substituted Thiazoles Bearing Piperazine Ring: Synthesis and Evaluation of their Anticancer Activity]]>https://benthamscience.comarticle/92075Background: Cancer cells are described as an unregulated growth and spread of abnormal cells. Recently, cancer has become the most important major reason for deaths in the world.

Methods: For anticancer activity, we have used the MTT method and determine the early/late apoptosis by flow cytometry.

Results: The title compounds were procured by reacting 2-chloro-N-[4-(pyridin-4-yl)thiazol-2- yl]acetamide with some substituted piperazine derivatives. The in vitro anticancer activity of synthesized compounds was tested against C6 rat glioma cells and A549 human lung carcinoma cells. As a result, the compounds 3d, 3e, 3f and 3g have shown anticancer activity against both cell line.

Conclusion: Specifically, compound 3f was determined as the most active compound against C6 rat glioma cells. Also, as understood, the core structure which is substituted with piperazine bridge, the heterocyclic aromatic derivatives are more active than phenyl or benzyl derivatives.

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<![CDATA[Metallodrugs in Targeted Cancer Therapeutics: Aiming at Chemoresistance- related Patterns and Immunosuppressive Tumor Networks]]>https://benthamscience.comarticle/86911 <![CDATA[Amino Acid Degrading Enzymes and their Application in Cancer Therapy]]>https://benthamscience.comarticle/86240

Objective: The purpose of this review was to summarize recent progress in the relationship between amino acids metabolism and cancer therapy, with a particular focus on Lasparagine, L-methionine, L-arginine and L-lysine degrading enzymes and their formulations, which have been successfully used in the treatment of several types of cancer.

Methods: We carried out a structured search among literature regarding to amino acid degrading enzymes. The main aspects of search were in vitro and in vivo studies, clinical trials concerning application of these enzymes in oncology.

Results: Most published research are on the subject of L-asparaginase properties and it’s use for cancer treatment. L-arginine deiminase has shown promising results in a phase II trial in advanced melanoma and hepatocellular carcinoma. Other enzymes, in particular Lmethionine γ-lyase and L-lysine α-oxidase, were effective in vitro and in vivo.

Conclusion: The findings of this review revealed that therapy based on amino acid depletion may have the potential application for cancer treatment but further clinical investigations are required to provide the efficacy and safety of these agents.]]> <![CDATA[Electronic Noses in Medical Diagnostics]]>https://benthamscience.comarticle/86205

Methods: Peer-reviewed research literature pertaining to the subject matter was identified based on a search of bibliographic databases. The quality and relevance of retrieved papers was assessed using standard tools. Their content was critically reviewed and certain information contained therein was compiled in tabularized form.

Results: The majority of reviewed studies show promising results, often surpassing the accuracy and sensitivity of established diagnostic methods. However, only a relatively small number of devices have been field tested. The methods used for sample collection and data processing in various studies were listed in a table, together with electronic nose models used in these investigations.

Conclusion: Despite the fact that devices equipped with arrays of chemical sensors are not routinely used in everyday medical practice, their prospective use would solve some established issues in medical diagnostics, as well as lead to developments in prophylactics by facilitating a widespread use of non-invasive screening tests.]]> <![CDATA[Meet Our Regional Editor]]>https://benthamscience.comarticle/96633 <![CDATA[Epigenetic Targets and their Inhibitors in Cancer Therapy]]>https://benthamscience.comarticle/95390 <![CDATA[How Inhaled Asbestos Causes Scarring and Cancer]]>https://benthamscience.comarticle/95503 <![CDATA[Diversity of Anticancer and Antimicrobial Compounds from Lichens and Lichen-derived Fungi: A Systematic Review (1985-2017)]]>https://benthamscience.comarticle/94387 <![CDATA[Inflammation and Cancer: In Medio Stat Nano]]>https://benthamscience.comarticle/85914 <![CDATA[Genistein Affects Expression of Cytochrome P450 (CYP450) Genes in Hepatocellular Carcinoma (HEPG2/C3A) Cell Line]]>https://benthamscience.comarticle/91604

Objective: The aim of this study was to investigate the effects of genistein on cytochrome P450 (CYP) gene expression levels in human hepatocellular carcinoma (HepG2/C3A) and colon adenocarcinoma (HT29) cells.

Methods: Real-time RT–PCR was used to examine the expression of genes families involved in xenobiotic metabolism, such as CYP1 (CYP1A1, CYP1B1), CYP2 (CYP2E1, CYP2D6), CYP3 (CYP3A4); and of a family involved in the catabolism of the all-trans-retinoic acid (ATRA), CYP26 (CYP26A1, CYP26B1).

Results: RT-qPCR data analysis showed that after 12 h of exposure of HepG2/C3A cells to genistein (5 and 50 µM) there was an upregulation of CYP1A1 and CYP1B1 and downregulation of CYP2D6, CYP26A1 and CYP26B1 mRNA levels. There was no change in the mRNA levels of CYP P450 genes in HT29 cells.

Conclusion: Our results suggest that treatment with genistein in non-toxic concentrations may impact the expression level of CYPs involved in the biotransformation of xenobiotics and drug metabolizing enzymes. Moreover, the downregulation of ATRA metabolism-related genes opens a new research path for the study of genistein as retinoic acid metabolism blocking agent for treating cancer and other pathologies.]]> <![CDATA[JQ1, a BET Inhibitor, Synergizes with Cisplatin and Induces Apoptosis in Highly Chemoresistant Malignant Pleural Mesothelioma Cells]]>https://benthamscience.comarticle/84368

Objective: We investigated if JQ1 could enhance the efficacy of cisplatin against MPM.

Methods: The antiproliferative activity of cisplatin in combination with JQ1 was assessed on MPM cell lines representative of the cellular phenotypes of this tumor (epithelioid, sarcomatoid and biphasic), and on one cisplatin resistant sub-line. The combination schedule was optimized adopting a 3Dspheroid model. Drug combination effects were correlated with cell cycle distribution and senescence- associated β-galactosidase positive cells. The expression of c-Myc and Fra-1 proteins and some apoptosis markers was assessed by immunoblotting and RT-qPCR. DNA damage and repair were evaluated by means of alkaline comet assay.

Results: JQ1 in combination with cisplatin elicited additive or synergistic (superadditive) antiproliferative effects on MPM cells, depending on the cell line. The combination showed tumor regression on the 3D-spheroid model. It induced increased apoptosis, along with decreased c-Myc and, sometimes, Fra-1 expression. JQ1 decreased cisplatin-induced DNA breaks in all MPM cells and increased senescence even in less proficient cells, thus enhancing the DNA Damage Response (DDR).

Conclusion: The superadditive effect is due to c-Myc repression. The consequent DDR enhancement triggers to apoptosis induction and/or permanent growth arrest (senescence), depending on the MPM cellular context, leading to tumor regression. Thus, the pharmacological modulation of BET activity could represent a promising tool for future MPM therapy.]]> <![CDATA[Role of miR-193a in Cancer: Complexity and Factors Control the Pattern of its Expression]]>https://benthamscience.comarticle/88978

Objective: This review aims to investigate the functional significance of miR-193a in different cancers according to the information of literature.

Method: All the literature concerning miR-193a in cancer in PubMed are analysed.

Results: Several studies proved the association of miR-193a expression patterns with cancer’s stages, grades, response to the chemotherapy and even patient survival. Also, miR-193a can be used to differentiate some types of cancer. In cancer, miR-193a can act as a tumour suppressor gene or as an oncogene. Till now, several genetic factors (MAX, RXR α, XB130, P63, P73, AEG-1, HIFs, EGFR, Drosha, DGCR8, Dicer) and epigenetic factors (DNA methylation and long non-coding RNAs) were predicted to control miR-193a expression. They have fundamental effects on its biological behaviour in different types of cancers.

Conclusion: miR-193a has significant roles in cancer and can be targeted in the future for cancer therapy by better understanding of the factors that control its biological behaviour.]]> <![CDATA[Systemic Treatment of Chest Tumors: Highlighting Some Differences Between Eastern and Western Countries]]>https://benthamscience.comarticle/88395

Conclusion: The approaches of this review are to highlight the recent management advances and contrast the differences of treatment practice between Western and Asian countries.]]> <![CDATA[Editorial: The Real Impact of Target Therapy in Cancer Patients: Between Hope and Reality]]>https://benthamscience.comarticle/90569 <![CDATA[Cancer Targeted Therapy Strategy: The Pathologist’s Perspectives]]>https://benthamscience.comarticle/87141

More in detail, neoplastic tissues of patients should display a specific biomarker, most often a specific genetic alteration and/or under/overexpression of a definite protein, that could be the target of its respective drug. Immunohistochemical and molecular analyses, which usually include examination of nucleic acids from either tissues or fluids, are common tests to define the status of a tumor.

This review focuses on the pathologist’s role in carefully controlling pre- analytic procedures and standard operating procedures that are a crucial prerequisite to reach reliable and reproducible results. Six paradigmatic applications of targeted therapy, for which pathological diagnosis plays a fundamental role, are summarized. Traditional and next-generation sequencing are also addressed from the pathologist's perspective as well as the importance pathologists have in this shift to more accurate definition of disease risk and prognostication of therapy response in the personalized medicine era.]]> <![CDATA[Functional Roles of the Ca2+-activated K+ Channel, KCa3.1, in Brain Tumors]]>https://benthamscience.comarticle/84753

Methods: We first describe the researches related to the role of KCa3.1 channels in the invasion of brain tumor cells and the regulation of cell cycle. In the second part we review the involvement of KCa3.1 channel in tumor-associated microglia cell behaviour.

Results: In tumor cells, the functional expression of KCa3.1 channels is important to substain cell invasion and proliferation. In tumor infiltrating cells, KCa3.1 channel activity is required to regulate their activation state. Interfering with KCa3.1 activity can be an adjuvant therapeutic approach in addition to classic chemotherapy and radiotherapy, to counteract tumor growth and prolong patient's survival.

Conclusion: In this mini-review we discuss the evidence of the functional roles of KCa3.1 channels in glioblastoma biology.]]> <![CDATA[Dyspnea in Cancer Patients: A Well-Known and Neglected Symptom]]>https://benthamscience.comarticle/89279

Methods: I reviewed the literature and guidelines on the topic with the aims to focus on what is known and on future pathways to follow for the diagnosis and treatment of dyspnea.

Results: There is no uniformity regarding the definition of dyspnea; consequently, there is still no general agreement about which tools are the best to use in clinical practice to detect the presence and severity of this symptom. In addition to the difficulty of assessing the symptom, a further limit concerns the management of dyspnea: a very limited number of therapies, both pharmacological and otherwise, are currently available that lead to satisfactory outcomes. Opioids such as morphine remain the cornerstone of treating dyspnea.

Conclusion: Dyspnea is a complex, multidimensional symptom that results from an interaction between factors and their causes, perception and expression. The main target of assessment and management is the intensity of dyspnea, as expressed by the patient, rather than the objective parameters of the disease. Although dyspnea is a very common symptom, debilitating and often difficult to control, especially in the terminal phase of the disease, few controlled studies have been conducted on cancer patients. Dyspnea remains a well-known but neglected symptom in advanced and terminal cancer patients. Future studies should be conducted regarding the careful assessment and management of this symptom.]]> <![CDATA[Overview on Anticancer Drug Design and Development]]>https://benthamscience.comarticle/87184

Objectives: This review helps to understand the rationale for the development of inhibitors against major targets such as cell growth, proliferation, survival, angiogenesis and recent targets such as proteasome, heat shock proteins, and epigenetics.

Methods: Recent approaches of the target-based anti-cancer drug developments were highlighted to giving some examples from approved agents. Many factors, such as metabolic change, hypoxia, cancer precursors and cancer resistant cells, and their effect on drug resistance mechanisms were discussed. The impacts of advanced computational techniques to identify targets of cancer and designing more selective inhibitors were explained.

Results: Contributions of recent techniques such as a network analysis, the precise modes of action and computational methodologies especially simulation of bio-molecular processes to clarify targets, mechanism actions and reasons of lack of efficacy of anti-cancer drugs have been explained. The relationship between the several mechanisms and molecular design strategies has been discussed.

Conclusion: This review provides an overview of important targets and design strategies of anti-cancer drugs, advantages and disadvantages of these methods and evaluation of some currently used anticancer targets in clinical studies.]]> <![CDATA[miRNA and Proteomic Dysregulation in Non-Small Cell Lung Cancer in Response to Cigarette Smoke]]>https://benthamscience.comarticle/87708

Objective and Methods: In this study, we carried out miRNA sequencing and SILAC-based proteomic analysis of H358 cells chronically exposed to cigarette smoke condensate. Using bioinformatics analysis, we mapped the dysregulated miRNAs to differentially expressed target proteins identified in our data. Gene ontology-based enrichment and pathway analysis was performed using the deregulated targets to study the role of cigarette smoke-mediated miRNA dysregulation in NSCLC cell line.

Results: miRNA sequencing resulted in the identification of 208 miRNAs, of which 6 miRNAs were found to be significantly dysregulated (2 fold, Log Base 2; p-value ≤ 0.05) in H358-Smoke cells. Proteomic analysis of the smoke exposed cells compared to the untreated parental cells resulted in the quantification of 2,610 proteins, of which 690 proteins were found to be differentially expressed (fold change ≥ 2). Gene ontology based analysis of target proteins revealed enrichment of proteins driving metabolism and a decrease in expression of proteins associated with immune response in the cells exposed to cigarette smoke. Pathway study using Ingenuity Pathway Analysis (IPA) revealed activation of NRF2-mediated oxidative stress response and actin-cytoskeleton signaling, and repression of protein kinase A signaling in H358-Smoke cells. We also identified 5 novel miRNAs in H358-Smoke cells using unassigned reads of small RNA-Seq dataset.

Conclusion: In summary, this study indicates that chronic exposure to cigarette smoke leads to widespread dysregulation of miRNAs and their targets, resulting in signaling aberrations in NSCLC cell line. The miRNAs and their targets identified in the study need to be further investigated to explore their role as potential therapeutic targets and/or molecular markers in NSCLC especially in smokers.]]> <![CDATA[miR-149 as a Potential Molecular Target for Cancer]]>https://benthamscience.comarticle/84828

Methods: An extensive literature search was conducted using the Pubmed database to sieve out articles related to the roles of miR-149 in carcinogenesis and cancer progression, and potential miRNA-based therapies. A total of 89 publications were selected for inclusion in this review.

Results: Depending on the cancer type, miR-149 can behave either as a tumor suppressor or as an ‘onco-miR' that promotes tumorigenesis and cancer spread, suggesting that this miRNA has diverse functions. Potential miRNA-based therapies include the use of miRNA mimics, miRNA inhibitors, demethylating agents and circular RNAs.

Conclusion: Although targeting miRNA is an attractive anti-cancer strategy, not all cancers can be treated by the same miRNA-based strategy. A comprehensive understanding of miRNA regulatory mechanism is also necessary to improve the design of miRNA-based therapeutics and there is a need for safe and efficient delivery methods when using this approach for anti-cancer treatment.]]> <![CDATA[Tumor-Targeting Peptides: Ligands for Molecular Imaging and Therapy]]>https://benthamscience.comarticle/82910 <![CDATA[Recent Advances in Antabuse (Disulfiram): The Importance of its Metal-binding Ability to its Anticancer Activity]]>https://benthamscience.comarticle/86483

Methods: We undertook a disulfiram-related search on bibliographic databases of peerreviewed research literature, including many historic papers and in vitro, in vivo, preclinical and clinical studies. The selected papers were carefully reviewed and summarized.

Results: More than five hundreds of papers were obtained in the initial search and one hundred eighteen (118) papers were included in the review, most of which deal with chemical and biological aspects of Disulfiram and the relationship of its chemical and biological properties. Eighty one (81) papers outline biological aspects of dithiocarbamates, and fifty seven (57) papers report biological activity of Disulfiram as an inhibitor of proteasomes or inhibitor of aldehyde dehydrogenase enzymes, interaction with other anticancer drugs, or mechanism of action related to reactive oxygen species. Other papers reviewed focus on chemical aspects of dithiocarbamates.

Conclusion: This review confirms the importance of chemical features of compounds such as Disulfiram to their biological activities, and supports repurposing DSF as a potential anticancer agent.]]> <![CDATA[The Beneficial Effects of Sulfur-containing Amino Acids on Cisplatininduced Cardiotoxicity and Neurotoxicity in Rodents]]>https://benthamscience.comarticle/84514

Objective: Beside the most commonly described nephro- and hepatotoxicity, cisplatin therapy is also accompanied with gastrointestinal, reproductive, hematological, cardiovascular and neurological side effects. Since it has been reported that cisplatin induce oxidative damage in various tissues, it seems reasonable to investigate an antioxidant supplementation as potential therapeutical approach for attenuation of cisplatin toxicities.

Methods: We performed a structured search of bibliographic databases for research literature using a focused review question and inclusion/exclusion criteria. The quality of retrieved papers (101 in total) was appraised using standard tools.

Results: Numerous antioxidants (such as thiol compounds, polyphenols, vitamins, etc.) had been reported for their beneficial effects on cisplatin-induced cardiotoxicity. The effects of various antioxidants, including sulfur-containing amino acids, have also been explored for mitigation of cisplatin neurotoxicity. However, the results for antioxidant supplementation in reduction of cisplatin-induced toxicities are still to be applied in clinical trials.

Conclusion: Considering the facts that sulfur-containing amino acids: (a) do not interfere with chemotherapeutics antitumor action; (b) do not exhibit any toxic effect (unless applied in dose several times above the recommended); and (c) produce significant protective effects on some cisplatin-induced toxicities connected to augmentation of oxidative damage - it seems that their administration can be harmless and protective supplementation against numerous adverse effects of certain antineoplastic agents.]]> <![CDATA[Notch Signalling Pathways and Their Importance in the Treatment of Cancers]]>https://benthamscience.comarticle/82213

Objective: In the present review, we highlight the Notch signalling pathway components i.e. Notch receptors, ligands, effector, and their regulators. We also discuss the tumor biology of the Notch pathway involved in various cancers.

Results: Interestingly, the Notch signalling pathway is dysregulated in many cancers. Notch may serve as oncogene or tumor suppressor and plays an important role in cancers of the liver, pancreas, endometrium of uterus, ovary, prostate, bladder and colon. The activation of Notch pathway plays a vital role in the progression of some cancer. In addition, Notch pathway activation was also shown to drive chemoresistance in cancer, as well. Chemotherapeutically, combined NOTCH1 inhibitor synergistically attenuated chemotherapy-enriched cancer stem cell population both in vitro and in vivo. This may prove to be beneficial in the treatment of cancer.

Conclusion: The Notch inhibitors possess anti-proliferative effects on cancer, thereby serving as a new treatment for cancer.]]> <![CDATA[Cancer-Targeted Oncolytic Adenoviruses for Modulation of the Immune System]]>https://benthamscience.comarticle/83193

In this review, we first highlight how oncolytic adenovirus interacts with the innate immune system and its receptors such as Toll-like receptors, nucleotide-binding and oligomerization domain (NOD)- like receptors and other immune sensors. Then we describe the effect of these interactions on the adaptive immune system and its cells, especially B and T lymphocytes. Finally, we summarize the most significant preclinical and clinical results in the field of gene therapy where researchers have engineered adenovirus to manipulate the host immune system by expressing cytokines and signalingmediators.]]> <![CDATA[Oncolytic Viruses: The Best is Yet to Come]]>https://benthamscience.comarticle/81523 <![CDATA[Clinical Trials with Oncolytic Measles Virus: Current Status and Future Prospects]]>https://benthamscience.comarticle/81932 <![CDATA[Epigenetics of Virus-Induced Tumors: Perspectives for Therapeutic Targeting]]>https://benthamscience.comarticle/85405

Epigenetics research allows better understanding of the complex interplay between oncoviruses and the host cells. This review highlights the importance of epigenetic reprogramming for virus-induced carcinogenesis. Recent progress in the development of pharmacological tools for targeting epigenetic mechanisms opens new perspectives for modulation of virus/host interaction and intervention of virus-induced cancer. Several clinical trials have been carried out or are on-going involving epigenetic drugs not only as single therapeutic but also in combination with other targeted agents against various virus-induced cancers.]]> <![CDATA[Multimodal HDAC Inhibitors with Improved Anticancer Activity]]>https://benthamscience.comarticle/81517 <![CDATA[Is there a Role for Epigenetic Enhancement of Immunomodulatory Approaches to Cancer Treatment?]]>https://benthamscience.comarticle/81520 <![CDATA[Epigenetic Modulation Using Small Molecules - Targeting Histone Acetyltransferases in Disease]]>https://benthamscience.comarticle/81961 <![CDATA[Chemical Space of FLT3 Inhibitors as Potential Anti-AML Drugs]]>https://benthamscience.comarticle/85045

Objective: This review focused on the progress of FLT3 inhibitors study including those that have entered clinical trials or were reported in numerous patents all over the world. Thus, we provided a useful reference for the development of new anti-leukemia drugs.

Method: Through a comprehensive retrospective study, FLT3 inhibitors in several patent applications were identified and classified into five categories, including quinolone-related, indole-related, ureas, pyrimidines and other compounds.

Results: For each category of compounds, the structural feature, SAR, biological activity and current research status were thoroughly reviewed and analyzed.

Conclusion: Although some of those compounds expressed potent bioactivities and have reached the advanced clinical trials for the treatment of leukemia, there are still several problems need to be faced before they enter the market eventually, especially the drug resistance issue. The improvement of therapeutic potency for FLT3 inhibitors might depend on the useful combination therapy and further refinement of the intrinsic properties of FLT3 inhibitors.]]> <![CDATA[Current and Emerging Therapy for Malignant Pleural Mesothelioma: Focus on CD26/Dipeptidyl Peptidase IV as a Therapeutic Target]]>https://benthamscience.comarticle/85634

Outline: In this review, the most current and up-to-date literature available was reviewed and the current state of malignant mesothelioma treatment is described. Throughout the review the need for new therapeutic approaches is highlighted in the shortcomings of current therapy. CD26 is a target that is fit to take on these shortcomings. In this review we discuss the structure and function of CD26, its role in malignant mesothelioma and the future of anti-CD26 therapy as a versatile immunotherapeutic option.

Conclusion: This review highlights the areas of most promise in treating MPM, these include immune checkpoint blockade, passive immunization, and based on our recently published data, targeting of CD26 with its specific mAb. Finally we describe how the anti-CD26 mAb YS110 was recently evaluated in the first-in-human phase I clinical trial, showing prolonged disease stabilization and a favorable side effect profile. Through better understanding of CD26, new pathways to treating and potentially curing malignant mesothelioma may be discovered.]]> <![CDATA[Engineered Peptides for Applications in Cancer-Targeted Drug Delivery and Tumor Detection]]>https://benthamscience.comarticle/73845 <![CDATA[Cardiac Tumors: Clinical Perspective and Therapeutic Considerations]]>https://benthamscience.comarticle/76967

Objective: Given that cardiac tumors exhibit some nonspecific symptoms compared with other heart diseases, clinical diagnosis of cardiac tumors is rather challenging. Thus we will try to review the classification and pathogenesis of cardiac tumors.

Conclusion: Current evidence revealed that 75% of cardiac tumors are considered benign (myxoma, fibromas, lipomas, rhabdomyomas, hemangiomas, teratomas, papillary fibroelastomas, pericardial cysts or cystic tumor of atrioventricular node). Clinical differential diagnosis of cardiac tumors is mainly based on imaging techniques including transthoracic and transesophageal echocardiograms, computed tomography (CT) scans and magnetic resonance imaging (MRIs). This mini-review tries to summarize recent understanding of the pathogenesis and therapeutics of cardiac tumors.]]> <![CDATA[Phosphoinositide-3-kinases as the Novel Therapeutic Targets for the Inflammatory Diseases: Current and Future Perspectives]]>https://benthamscience.comarticle/78902

Background: Recent findings have publicized phosphoinositide-3-kinases (PI3Ks) as novel therapeutic targets, which are also purported to be involved in the complex pathophysiology of inflammatory and various other diseases. They are recognized to participate in the inflammatory cellular responses by modulating the growth, development and proliferation of various immune cells and hence, affect the release of various cytokines and other inflammatory mediators involved in these manifestations. The recent literature relating this pathway with these diseases is highlighted, with a hope, which remains for the progression of PI3K inhibitors in the market as a treatment option.

Result: With Idelalisib entering the market for cancer, PI3K/AKT signalling has also gained significance as an investigational target for various diseases, particularly for inflammation. Based on the pharmacological, genetic, and clinical data available, PI3K/AKT signalling can be designated as an outstanding target for their treatment.

Conclusion: Further exploration of this pathway may also uncover its involvement in these disorders, which may further contribute to developing the new treatments and can turn out to be an innovative brainwave in the field of experimental and clinical pharmacology in future.]]> <![CDATA[Major Highlights of the CAR-TCR Summit, Boston, 2016]]>https://benthamscience.comarticle/80954 <![CDATA[Potential Role of Natural Compounds as Anti-Angiogenic Agents in Cancer]]>https://benthamscience.comarticle/84745

Methods: In this article, we briefly review the various mediators involved in the angiogenic process and the anti-angiogenic potential of selected natural compounds against various malignancies.

Results: Several growth factors and their receptors such as vascular endothelial growth factor and receptor (VEGF/VEGFR), basic fibroblast growth factor and receptor (bFGF/FGFR), angiopoietins, and hypoxia inducible factors facilitate the development of angiogenesis and are attractive anti-cancer targets. Natural products represent a rich diversity of compounds for drug discovery and are currently being actively exploited to target tumor angiogenesis.

Conclusion: Agents such as curcumin, artemisinin, EGCG, resveratrol, emodin, celastrol, thymoquinone and tocotrienols all have shown prominent anti-angiogenic effects in the preclinical models of tumor angiogenesis. Several semi-synthetic derivatives and novel nano-formulations of these natural compounds have also exhibited excellent anti-angiogenic activity by increasing bioavailability and delivering the drugs to the sites of tumor angiogenesis.]]> <![CDATA[Neurochemical Markers in the Mammalian Brain: Structure, Roles in Synaptic Communication, and Pharmacological Relevance]]>https://benthamscience.comarticle/82840

Objective: Here, we survey 15 prominent neurochemical markers from five categories, namely membrane transporters, calcium-binding proteins, neuropeptides, receptors, and extracellular matrix proteins, explaining their relation and relevance to synaptic communication.

Method: For each marker, we summarize fundamental structural features, cellular functionality, distributions within and outside the brain, as well as known drug effectors and mechanisms of action.

Conclusion: This essential primer thus links together the cellular complexity of the brain, the chemical properties of key molecular players in neurotransmission, and possible biomedical opportunities.]]> <![CDATA[Immune Checkpoints Aberrations and Malignant Mesothelioma: Assessment of Prognostic Value and Evaluation of Therapeutic Potentials]]>https://benthamscience.comarticle/80750 <![CDATA[Poly (ADP-Ribosyl) Polymerase 1 Inhibitors: A Patent Review]]>https://benthamscience.comarticle/83333

Objective: Present review aims to introduce PARP1 inhibitors by their structures and try to point out future development direction of PARP1 inhibitors.

Method: Details regarding the PARP1and PARP1 inhibitors are obtained from PubMed literatures and patent databases.

Conclusion: The action mode of PARP1 inhibitors developed so far is competing with NAD+ for the catalytic site of PARP1. Using such inhibitors affects multiple NAD+-dependent enzymatic pathways, which results in secondary toxic effects. Designing inhibitors targeting other binding sites on the PARP1 protein is a strategy to bypass this pitfall. Analyzing the structure-activity relationships of active PARP1 inhibitors described in the patents, we conclude that for the binding activity, amide group, aromatic ring or heterocyclic ring with rich electronics and heteroatom-substituted in the meta position of amide group are essential. Big substituents introduced in the heterocyclic ring can enhance inhibitory activity and improve solubility or other physicochemical properties. Clinical trials of PARP1 inhibitor were focused on cancer therapies and have achieved remarkable results.]]>
<![CDATA[Recent Advances in Oncological Submissions of Dendrimer]]>https://benthamscience.comarticle/82552

Methods: Dendrimer mediated cancer therapy is advantageous over conventional chemotherapy, radiotherapy and surgical resection due to reduced systemic toxicity, and molecular level cell injury to cancerous mass, for an appreciable survival of the subject. Recently used dendrimer mediated nanotechnology for oncology aims to conquer these challenges. Dendrimers based nano-constructs are having architectures comparable to that of biological vesicles present in the human body.

Results: Operating with dendrimer technology, proffers the exclusive and novel strategies with numerous applications in cancer management involving diagnostics, therapeutics, imaging, and prognostics by sub-molecular interactions. Dendrimers are designed to acquire the benefits of the malignant tumor morphology and characteristics, i.e. leaky vasculature of tumor, expression of specific cell surface antigen, and rapid proliferation.

Conclusion: Dendrimers mediated targeted therapy recommends innovatory function equally in diagnostics (imaging, immune-detection) as well as chemotherapy. Currently, dendrimers as nanomedicine has offered a strong assurance and advancement in drastically varying approaches towards cancer imaging and treatment. The present review discusses different approaches for cancer diagnosis and treatment such as, targeted and control therapy, photodynamic therapy, photo-thermal therapy, gene therapy, antiangiogenics therapy, radiotherapy etc.]]>
<![CDATA[Bioconjugation of Ionophore Antibiotics: A Way to Obtain Hybrids with Potent Biological Activity]]>https://benthamscience.comarticle/83526 <![CDATA[Meet Our Editorial Board Member]]>https://benthamscience.comarticle/85279 <![CDATA[Carbon Nanotubes in the Treatment of Skin Cancers: Safety and Toxic ological Aspects]]>https://benthamscience.comarticle/82041

Objective: The present review aims to explore a novel nano-sized carrier, carbon nanotubes for the delivery of various actives researched for skin cancer treatment. The write up traces the pre-clinical and clinical reports on carbon nanotubes. The feasibility of the nanoparticulate system has been elaborated inclusive of the safety and toxicological aspects of the carrier system.

Conclusion: From the reviewed literature it can be concluded that carbon nanotubes are the emerging treatment modality in skin cancers as they offer targeted delivery to the cancerous cells, act selectively and provide better penetration in the neoplastic cells due to improved permeability and retention effect.

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<![CDATA[Antimicrobial, Biofilm Inhibitory and Anti-infective Activity of Metallic Nanoparticles Against Pathogens MRSA and Pseudomonas aeruginosa PA01]]>https://benthamscience.comarticle/82979

Objective: In the present study, the metallic nanoparticles (iron, gold, zinc oxide and copper oxide) were evaluated for the antimicrobial, biofilm inhibitory and anti-infective activity against human pathogens methicillin resistant Staphylococcus aureus and Pseudomonas aeruginosa PA01.

Methods: The efficacy of nanoparticles on the planktonic growth of clinically relevant pathogens was determined by MIC. Further, the effect of nanoparticles was studied on their biofilms using crystal violet microtiter plate assay and fluorescent microscopy. The cytotoxicity of nanoparticles was studied in HT29 cell line.

Results: The nanoparticles of copper and zinc oxide (size < 50 nm) were more effective against Grampositive and Gram-negative pathogens in comparison to gold and iron nanoparticles. The ZnO nanoparticles had an MIC in the range of 3.125 μg/ ml and 6.25 μg/ ml against the tested pathogens. The nanoparticles at the tested concentration reduced biofilm burden by > 75% in the pathogens. The nanoparticles showed cytotoxicity in HT 29 at 20 μg/ ml.

Conclusion: The results of the study showed that of all the tested nanoparticles, ZnO nanoparticles had significant antimicrobial activity against the drug resistant pathogens and could be used at concentrations less toxic to mammalian cells. Hence, ZnO nanoparticles have the potential for the design of novel antibacterial agents and therapeutics.

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<![CDATA[Interferon Therapy in Lung Cancer: Current Perspectives]]>https://benthamscience.comarticle/82334

Material: Interferon supplement or its use in combination with other anti-cancer drugs are thought of and investigated around the globe with some promising results on hand. Interferons have been found to be effective in reducing the growth of tumor and also in triggering the anti-tumor immune response in humans.

Method: Interferon therapy is being found to be effective against various types of cancer including lung cancer. Lung cancer is one of the most difficult cancers to deal clinically as it remains asymptomatic till metastasis in most of the cases. Depending on the appearance of pulmonary cancer cells under microscope, lung cancer has primarily been classified into small cell lung cancer and non-small cell lung cancer.

Conclusion: Interferons have been found to be effective in both types of lung cancer even in advanced stage. IFN α & β (type I IFN) have been extensively tried in various experimental models of lung cancer and clinical cases and have been found to be effective while other types and sub types of interferon like IFN gamma have also been tried in several cases of lung cancer and have yielded varied results. Studies are still in progress and we are looking ahead for further achievements related to potential and effective interferon therapy against pulmonary malignancies.

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<![CDATA[Cancer Bioinformatics for Updating Anticancer Drug Developments and Personalized Therapeutics]]>https://benthamscience.comarticle/81669

Methods: Same as other biological techniques or systems, bioinformatics techniques will be widely used. But they are presently not omni-potent. Despite great popularity and improvements, cancer bioinformatics has its own limitations and shortcomings at this stage of technical advancements.

Results: This article will offer a panorama of bioinformatics in cancer researches and clinical therapeutic applications-possible advantages and limitations relating to cancer therapeutics. A lot of beneficial capabilities and outcomes have been described. As a result, a successful new era for cancer bioinformatics is waiting for us if we can adhere on scientific studies of cancer bioinformatics in malignant- origin mining, medical verifications and clinical diagnostic applications.

Conclusion: Cancer bioinformatics gave a great significance in disease diagnosis and therapeutic predictions. Many creative ideas and future perspectives are highlighted.

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<![CDATA[Exploring Mechanisms of MicroRNA Downregulation in Cancer]]>https://benthamscience.comarticle/80245 <![CDATA[Bortezomib Enhances the Antitumor Effects of Interferon-β Gene Transfer on Melanoma Cells]]>https://benthamscience.comarticle/78518

Objective: Both interferon-β (IFNβ) and bortezomib (BTZ) display inhibitory activities on melanoma cells. Here, we evaluated the cytotoxic effects of the combination of BTZ and IFNβ gene lipofection on cultured melanoma cell lines.

Method: Cell viability determined by the acid phosphatase method, cell migration mesasured by the wound healing assay, DNA fragmentation and cell cycle by flow cytometry after propidium iodide staining and reactive oxygen species (ROS) production by H2DCF-DA fluorescence.

Results: Four canine mucosal (Ak, Br, Bk and Ol) and two human dermal (A375 and SB2) melanoma cell lines were assayed. BTZ sub-pharmacological concentrations (5 nM) enhanced the cytotoxic effects of IFNβ transgene expression on melanoma cells monolayers and spheroids. The combination was also more effective than the single treatments when assayed for clonogenic survival and cell migration. The combined treatment produced a significant raise of apoptosis evidenced by DNA fragmentation as compared to either BTZ or IFNβ gene lipofection single treatments. Furthermore, BTZ significantly increased the intracellular ROS generation induced by IFNβ gene transfer in melanoma cells, an effect that was reversed by the addition of the ROS inhibitor N-acetyl-L-cystein.

Conclusion: The present work encourages further studies about the potential of the combination of interferon gene transfer with proteasome inhibitors as a new combined therapy for malignant melanoma, both in veterinary and/or human clinical settings.

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<![CDATA[Tip60: Main Functions and Its Inhibitors]]>https://benthamscience.comarticle/78529

Results: Dysfunction of Tip60 could promote or suppress diseases including different kinds of cancers.

Conclusion: Here, main functions and its known inhibitors were summarized.

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<![CDATA[Mechanisms of Tubulin Binding Ligands to Target Cancer Cells: Updates on their Therapeutic Potential and Clinical Trials]]>https://benthamscience.comarticle/78641

Objective: In the current review article, plausible mechanistic details about the interactions of ligands at the binding pocket and subsequent changes in the tubulin structure are described. The review article also illustrated different formulations of the tubulin binding agents in combination with other chemotherapeutic agents and their therapeutic potential against various human malignancies.

Conclusion: Tubulin targeting agents emerged as one of the most successful anticancer drugs and a number of structurally different chemical compounds are in advance stages of clinical development.

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<![CDATA[Tumour-Derived Glutamate: Linking Aberrant Cancer Cell Metabolism to Peripheral Sensory Pain Pathways]]>https://benthamscience.comarticle/75522

Methods: This review focuses on how up-regulated glutamate production and export by the tumour converge at peripheral afferent nerve terminals to transmit nociceptive signals through the transient receptor cation channel, TRPV1, thereby initiating central sensitization in response to peripheral disease-mediated stimuli.

Results: Cancer cells undergo numerous metabolic changes that include increased glutamine catabolism and over-expression of enzymes involved in glutaminolysis, including glutaminase. This mitochondrial enzyme mediates glutaminolysis, producing large pools of intracellular glutamate. Upregulation of the plasma membrane cystine/glutamate antiporter, system xc -, promotes aberrant glutamate release from cancer cells. Increased levels of extracellular glutamate have been associated with the progression of cancer-induced pain and we discuss how this can be mediated by activation of TRPV1.

Conclusion: With a growing population of patients receiving inadequate treatment for intractable pain, new targets need to be considered to better address this largely unmet clinical need for improving their quality of life. A better understanding of the mechanisms that underlie the unique qualities of cancer pain will help to identify novel targets that are able to limit the initiation of pain from a peripheral source–the tumour.

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<![CDATA[Green Chemistry Approach as a Versatile Platform for Nanoparticles with Biomedical Applications]]>https://benthamscience.comarticle/82240 <![CDATA[Modulation of the Type I Interferon Response Defines the Sensitivity of Human Melanoma Cells to Oncolytic Measles Virus]]>https://benthamscience.comarticle/80723

Objective: Our study aims at determining which parameters define the sensitivity of human melanoma cells to oncolytic MV infection.

Methods: We analyzed both in vitro and in vivo the oncolytic activity of MV against a panel of human melanoma cell established in our laboratory. We tested whether either type I interferons or the interferon pathway inhibitor Ruxolitinib could modulate the sensitivity of these cells to oncolytic MV infection.

Results: Human melanoma cells exhibit varying levels of sensitivity to MV infection in culture and as tumor xenografts. As these differences are not explained by their expression level of the CD46 receptor, we hypothesized that antiviral immune responses may be suppressed in certain cell resulting in their inability to control infection efficiently. By analyzing the type I IFN response, we found that resistant cells had a fully functional pathway that was activated upon MV infection. On the contrary, sensitive cell showed defects in this pathway. When pre-treated with IFN-α and IFN-β, all but one of the sensitive cell became resistant to MV. Cells resistant to MV were rendered sensitive to MV with Ruxolitinib. Conclusion: Type I interferon response is the main determinant for the sensitivity or resistance of melanoma to oncolytic MV infection. This will have to be taken into account for future clinical trials on oncolytic MV.

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<![CDATA[Intrinsic Disorder in Male Sex Determination: Disorderedness of Proteins from the Sry Transcriptional Network]]>https://benthamscience.comarticle/79357 <![CDATA[New Poly(3-hydroxybutyrate) Microparticles with Paclitaxel Sustained Release for Intraperitoneal Administration]]>https://benthamscience.comarticle/75375

Objective: This study was conducted to develop new prolong paclitaxel (PTX) formulation based on poly(3- hydroxybutyrate) (PHB) microparticles.

Method: PHB microparticles loaded with antitumor cytostatic drug PTX were obtained by spray-drying method using Nano Spray Dryer B-90. The PTX release kinetics in vitro from PHB microparticles and their cytotoxity on murine hepatoma cell line MH-22a were studied. Microparticles antitumor activity in vivo was studied using intraperitoneally (i.p.) transplanted tumor models: murine Lewis lung carcinoma and xenografts of human breast cancer RMG1.

Results: Uniform PTX release from PHB-microparticles during 2 months was observed. PTX-loaded PHB microparticles have demonstrated a significant antitumor activity versus pure drug both in vitro in murine hepatoma cells and in vivo when administered i.p. to mice with murine Lewis lung carcinoma and xenografts of human breast cancer RMG1.

Conclusion: The developed technique of PTX sustained delivery from PHB-microparticles has therapeutic potential as prolong anticancer drug formulation.

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<![CDATA[Hypoxia and Inflammation in Prostate Cancer Progression. Cross-talk with Androgen and Estrogen Receptors and Cancer Stem Cells]]>https://benthamscience.comarticle/80059 <![CDATA[Comparative Proteomics and Bioinformatics Analysis of Tissue from Non-Small Cell Lung Cancer Patients]]>https://benthamscience.comarticle/80196

Materials and Methods: In this study, we aimed to identify proteome level differences between NSCLC tumor and tumor-adjacent non-tumor tissue samples using gel-based comparative proteomics.

Additionally, proteins were classified using PANTHER, protein-protein interactions were mapped by STRING, and also, the top canonical pathway was identified using IPA network system. Western blot was used for validation the proteomics findings.

Results: A total of 40 protein spots were successfully identified by MALDI-TOF/TOF, and 33 proteins were found differentially expressed, of which 27 proteins were up-regulated, whereas, 6 proteins were down-regulated in NSCLC tumor tissues.

Conclusion: These findings show that proteome level differences between NSCLC tumor and nontumor tissue samples.]]> <![CDATA[Melanoma]]>https://benthamscience.comarticle/81038 <![CDATA[Surgical Options for Management of Malignant Pleural Mesothelioma in the Current Era]]>https://benthamscience.comarticle/80714 <![CDATA[Epidemiology and Pathology of Malignant Mesothelioma]]>https://benthamscience.comarticle/77845 <![CDATA[Chimeric Antigen Receptor T Cells: Self-Replicating Drugs for Cancer]]>https://benthamscience.comarticle/69833 <![CDATA[New Approaches to Photodynamic Therapy from Types I, II and III to Type IV Using One or More Photons]]>https://benthamscience.comarticle/75675 <![CDATA[Potential of Taming MicroRNA on Driver Seat to Control Mitochondrial Horses in Breast Carcinoma]]>https://benthamscience.comarticle/77369 <![CDATA[First Molecular Cytogenetic Characterization of Murine Malignant Mesothelioma Cell Line AE17 and In Silico Translation to the Human Genome]]>https://benthamscience.comarticle/76294

Objective: Provide first genetic characterization of murine MM cell line AE17, translate into human genome and characterize the human subtype of MM AE17 is suited as a model.

Method: AE17 was studied on chromosomal level by molecular cytogenetics and array comparative genomic hybridization.

Results and Conclusion: AE17 did not tetraploidize yet, has a basic karyotype of 40 chromosomes with only 3 balanced inversions, one balanced translocation and five chromosomes with simple to complex rearrangements, leading in the end to partial chromosomal deletions. Besides one stemline, three additional subclones could be observed. The obtained data was, by means of bioinformatics based on silico translation of the detected imbalances and observed chromosomal breakpoints, translated to the human genome. The obtained data suggests that AE17 is a well suited cell line model for MM with (cyto)genetic changes characteristic for sarcomatoid MM form. Furthermore, genes ESR2 and BAK1 seem to be activated in one of the subclones of AE17, which also could be of interest for future studies. Overall, the present data could only be obtained through bioinformatics based on silico analyses, to cope with the microarray data and also for browser based translation of murine into human genome.

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<![CDATA[Occupational Risk Assessment of Engineered Nanomaterials: Limits, Challenges and Opportunities]]>https://benthamscience.comarticle/78975

Objective: The aim of this review was to address those critical aspects that currently prevent the achievement of a suitable risk evaluation in order to point out priorities of research helpful to develop and implement an effective guidance for nano-risk assessment.

Method: Literature search concerning NM physico-chemical characterization, toxicological behavior and exposure assessment strategies was analyzed to extrapolate opportunities, challenges and criticisms in the application of the general chemical risk assessment steps to the nano-sized toxicological field.

Results: Uncertainties on the role of the physico-chemical properties in nanomaterial toxicity, the complexity in extrapolating dose-response relationships, and practical difficulties in measuring nanomaterial exposure emerged as challenging issues for the application of a traditional risk assessment approach to nano-sized exposures.

Conclusion: Future investigations on these topics appear necessary to define an effective, nanofocused risk evaluation strategy that should be dynamically improved and verified as more substantial information become available. Such a suitable risk assessment process should provide adequate estimates of nanomaterial risks to guide the adoption of appropriate risk communication and management strategies for the protection and the safety of the workers.

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IGF2 belongs to the most complexly regulated growth factors known. As an imprinted gene it is controlled by epigenetic alterations. IGF2 mRNA binding proteins (IMPs/IGF2BPs) further regulate its translation. IGF2 activity is contained through IGF binding proteins (IGFBPs) and differential expression of the target receptors. The necessity of such a complex regulation implies pathophysiological effects of a deregulated expression of IGF2. This review attempts to summarize the different levels of IGF2 regulation, especially in the context of cancer. Members of the IGF2 axis are enlightened from the perspective of novel molecular targets for cancer therapy. Preclinical as well as experimental therapeutic interventions targeting IGF2 in cancer will be surveyed. ]]> <![CDATA[Determinants of Anti-Cancer Effect of Mitochondrial Electron Transport Chain Inhibitors: Bioenergetic Profile and Metabolic Flexibility of Cancer Cells]]>https://benthamscience.comarticle/77141