<![CDATA[Sarcoma]]> https://benthamscience.com RSS Feed for Disease Wise Article | BenthamScience EurekaSelect (+http://eurekaselect.com) Fri, 29 Mar 2024 12:25:13 +0000 <![CDATA[Sarcoma]]> 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[New Perspectives in the Pharmacological Potential of Naringin in Medicine]]>https://benthamscience.comarticle/107112Background: Naringin (NAR) is a flavonoid enriched in several medicinal plants and fruits. An increasing interest in this molecule has emerged because it has the potential to contribute to alleviating many health problems.

Objective: This review briefly describes the NAR pharmacokinetics and it mainly focuses on the in vitro and in vivo animal studies showing NAR beneficial effects on cardiovascular, metabolic, neurological and pulmonary disorders and cancer. The anabolic effects of NAR on different models of bone and dental diseases are also analyzed. In addition, the evidence of the NAR action on the gastrointestinal tract is reported as well as its influence on the microbiota composition and activity. Finally, current research on NAR formulations and clinical applications are discussed.

Methods: The PubMed database was searched until 2019, using the keywords NAR, naringenin, cardiovascular and metabolic disorders, neurological and pulmonary disorders, cancer, bone and dental diseases, gastrointestinal tract, microbiota, NAR formulations, clinical trials.

Results: The number of studies related to the bioavailability and pharmacokinetics of NAR is limited. Positive effects of NAR have been reported on cardiovascular diseases, Type 2 Diabetes Mellitus (T2DM), metabolic syndrome, pulmonary disorders, neurodegenerative diseases, cancer, and gastrointestinal pathologies. The current NAR formulations seem to improve its bioavailability, which would allow its clinical applications.

Conclusion: NAR is endowed with broad biological effects that could improve human health. Since a scarce number of clinical studies have been performed, the NAR use requires more investigation in order to know better their safety, efficacy, delivery, and bioavailability in humans.

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<![CDATA[Dual-target Inhibitors Based on BRD4: Novel Therapeutic Approaches for Cancer]]>https://benthamscience.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[Recent Progress in the Development of Quinoline Derivatives for the Exploitation of Anti-Cancer Agents]]>https://benthamscience.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://benthamscience.comarticle/107243 <![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[Cholesterol: A Prelate in Cell Nucleus and its Serendipity]]>https://benthamscience.comarticle/105775 <![CDATA[Flavonoids and other Non-alkaloidal Constituents of Genus Erythrina: Phytochemical Review]]>https://benthamscience.comarticle/107215Background: Genus Erythrina belongs to family Fabaceae, which is widely distributed in tropical and subtropical areas. It has been used in both traditional herbal medicines and pharmacological applications. Original research articles and publications on the overview of alkaloids related to this genus are available, but a supportive systematic review account which highlighted phytochemical aspects of other types of secondary metabolites is currently insufficient.

Objective: With the utilization of data and information from SCI-Finder, Google Scholar, the Web of Science, Scopus, Science Direct, PubMed, Chemical Abstracts, ACS journals, Springer, Taylor Francis, Bentham Science and IOP Science, the reliable material sources of this systematic review paper were obtained from the literature published from the 1980s to now.

Conclusion: A vast amount of data showed that the non-alkaloidal secondary metabolites were obtained from genus Erythrina with various classes of chemical structures. Herein, approximately five hundred constituents were isolated, comprising flavonoids, terpenoids, saponins, phytosterols, phenols, arylbenzofurans, coumarins, alcohols, ceramides, mono-sugars and fatty acid derivatives. In agreement with the previous phytochemical reports on the plants of the family Fabaceae, flavonoids reached a high amount in the plants of genus Erythrina. Numerous biological activity investigations such as anti-bacteria, anti-cancer, anti-virus using isolated compounds from Erythrina species suggested that secondary metabolites of Erythrina plants are now becoming the promising agents for drug developments.

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<![CDATA[Complications of Muscle Hematomas in Hemophilia]]>https://benthamscience.comarticle/105833 <![CDATA[Exopolysaccharide Produced from <i>Rhizobium</i> spp. - An Interesting Product for Industry and Environment]]>https://benthamscience.comarticle/101537 <![CDATA[Denouement of Chemicals on Amyotrophic Lateral Sclerosis: Is Green Chemistry the Answer]]>https://benthamscience.comarticle/105774 <![CDATA[Immunoliposomes: Synthesis, Structure, and their Potential as Drug Delivery Carriers]]>https://benthamscience.comarticle/104878 <![CDATA[The Radio-Sensitizing Effect of Pharmacological Concentration of Ascorbic Acid on Human Pancreatic Cancer Cells]]>https://benthamscience.comarticle/107304Background: Previous studies reported the inevitable destructive effects of radiotherapy on normal adjacent cells. Ascorbic Acid (AA) has been proposed as an effective anti-cancer agent with no obvious effects on normal cells.

Objective: The effects of Ascorbic acid in combination with radiotherapy on human pancreatic carcinoma cell line were studied.

Methods: The human pancreatic cancer cells were cultured and divided into four groups: control group (A) without any treatment, group B that received 2Gy radiotherapy alone, group C that was treated with 4mM AA alone, and group D that was co-treated with AA and radiotherapy. Cell viability, DNA fragmentation, expression of apoptotic genes, and Reactive Oxygen Species (ROS) production were determined in treated cells.

Results: There was a noticeable decrease in cell viability after treatment with AA (and/or) radiotherapy. All treated groups showed elevated ROS production, Bax/Bcl2 expression, DNA fragmentation, and cytotoxycity compared with the control group. Cells under combination therapy showed the most cytotoxicity.

Conclusion: The results suggest that AA at a dose of 4mmol/l may be used as an effective radio-sensitizing agent in pancreatic cancer cell line.

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<![CDATA[Anticancer Activity of Lectins from <i>Bauhinia purpurea</i> and <i>Wisteria floribunda</i> on Breast Cancer MCF-7 Cell Lines]]>https://benthamscience.comarticle/105732 Objective: To study the antiproliferative activity of two N-acetyl galactosamine specific plant lectins from seeds of Bauhinia purpurea and Wisteria floribunda against MCF-7 Breast cancer cell lines.

Methods: MTT, lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS), and caspase- 3 assays and flow cytometry for cell cycle analysis were performed.

Results: The agglutinins BPL and WFL; 446 μgml-1 (2.2 μM) and 329 μgml-1 (2.8 μM), respectively caused remarkable concentration-dependent antiproliferative effect on MCF-7. The effect was seen to be a consequence of binding of the lectin to the cell surface and triggering S and G2 phase arrest. Apoptosis induced was found to be associated with LDH leakage, cell cycle arrest and ROS generation. The apoptotic signal was observed to be amplified by activation of caspase-3 resulting in cell death.

Conclusion: The study provides a base for detailed investigation and further use of lectins in cancer studies.]]>
<![CDATA[Genotype Driven Therapy for Non-Small Cell Lung Cancer: Resistance, Pan Inhibitors and Immunotherapy]]>https://benthamscience.comarticle/96827 <![CDATA[The Epigenetic Modification of Epigallocatechin Gallate (EGCG) on Cancer]]>https://benthamscience.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[Bone Marrow Culture Yield for the Diagnosis of Opportunistic Diseases in Patients with AIDS and Disseminated Kaposi Sarcoma]]>https://benthamscience.comarticle/107070

Objective: The aim of this study was to evaluate the utility of BM aspirate and biopsy in patients with DKS.

Methods: We included 40 male patients with a recent diagnosis of DKS. BM aspirate and biopsy was performed as part of the workup to rule out co-infections.

Results: In four patients, Mycobacterium avium complex (MAC) was recovered from culture. In other four patients, intracellular yeasts were observed in the Grocott stain, diagnosed as Histoplasma. The yield of BM was calculated in 20%. Only 12 patients (30%) had fever and 11 (27.5%) had pancytopenia. Alkaline phosphatase (ALP) above normal values and C-reactive protein (CRP) were higher in patients with positive results for BM than in those with negative results (63% vs. 21.9%, and 3.0 vs. 1.2 mg/L; p = 0.03 in both comparisons). No differences were found when complete blood-count abnormalities were compared.

Conclusion: We recommend performing a BM aspirate for stains, culture, and biopsy in all HIV patients with DKS, as this will permit the early diagnosis of co-infections and prevent further complications in those who receive chemotherapy.]]>
<![CDATA[Exploring siRNA Umpired Nanogels: A Tale of Barrier Combating Carrier]]>https://benthamscience.comarticle/105883 <![CDATA[Cyanidin 3-O-Glucoside Induces the Apoptosis in the Osteosarcoma Cells through Upregulation of the PPARγ and P21: An <i>In Vitro</i> Study]]>https://benthamscience.comarticle/105708

Objective: In this study, the apoptotic effects of C3G on three different osteosarcoma cell lines including Saso-2, MG-63, and G-292 (clone A141B1) were investigated.

Methodology: The 24-hr IC50 of C3G for Saso-2, G-292, and MG-63 cells was evaluated by the MTT assay. Apoptosis induction in these cell lines after treatment with the C3G was approved by the Annexin V/PI flow cytometry. Changes at the mRNA expression level of PPARγ, P21, Bax, and Bcl-xl genes were investigated by real-time Polymerase Chain Reaction (PCR) technique, and P21 expression was further confirmed by the western blotting.

Results: The MTT assay results demonstrated that the 24-hr IC50 of C3G was equal to 110μg/ml for Saso-2 and G-292 cells while it was about 140μg/ml for the MG-63 cells. The results of real-time PCR clearly showed that treatment of the cells with 24hrs IC50 of C3G caused the upregulation of PPARγ, P21, and Bax genes. Moreover, western blot analysis confirmed that P21 protein overexpressed endogenously after treatment of the cells with the C3G, and it was more upregulated in the MG-63 cells compared to the other cell lines.

Conclusion: According to the findings of the study, the C3G is a novel anti-osteosarcoma agent with the ability to induce the apoptosis in different osteosarcoma cells through upregulation of the PPARγ and P21 genes.]]>
<![CDATA[Modulating Pluripotency Network Genes with Omega-3 DHA is followed by Caspase- 3 Activation and Apoptosis in DNA Mismatch Repair-Deficient/KRAS-Mutant Colorectal Cancer Stem-Like Cells]]>https://benthamscience.comarticle/104933Background: Targeting DNA mismatch repair-deficient/KRAS-mutant Colorectal Cancer Stem Cells (CRCSCs) with chemical compounds remains challenging. Modulating stemness factors Bmi-1, Sox-2, Oct-4 and Nanog in CRCSCs which are direct downstream targets of carcinogenesis pathways may lead to the reactivation of caspase-3 and apoptosis in these cells. Omega-3 DHA modulates different signaling pathways involved in carcinogenesis. However, little is known, whether in vitro concentrations of DHA equal to human plasma levels are able to modulate pluripotency genes expression, caspase-3 reactivation and apoptosis in DNA mismatch repair-deficient/KRAS-mutant CRC stem-like cells.

Methods: DNA mismatch repair-deficient/KRAS-mutant CRC stem-like cells (LS174T cells) were treated with DHA, after which, cell number and proliferation-rate, Bmi-1, Sox-2, Nanog and Oct-4 expression, caspase-3 activation and apoptosis were evaluated with different cellular and molecular techniques.

Results: DHA changed the morphology of cells to apoptotic forms and disrupted cell connections. After 48h treatment with 50- to 200μM DHA, cell numbers and proliferation-rates were measured to be 86%-35% and 93.6%-45.7% respectively. Treatment with 200 μM DHA dramatically decreased the expression of Bmi-1, Sox- 2, Oct-4 and Nanog by 69%, 70%, 97.5% and 53% respectively. Concurrently, DHA induced caspase-3 activation by 1.8-4.7-fold increases compared to untreated cells. An increase in the number of apoptotic cells ranging from 9.3%-38.4% was also observed with increasing DHA concentrations.

Conclusions: DHA decreases the high expression level of pluripotency network genes suggesting Bmi-1, Sox-2, Oct-4 and Nanog as promising molecular targets of DHA. DHA reactivates caspase-3 and apoptosis in DNA mismatch repair-deficient/KRAS-mutant CRC stem-like cells, representing the high potential of this safe compound for therapeutic application in CRC.

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<![CDATA[Roles of Medicinal Plants and Constituents in Gynecological Cancer Therapy: Current Literature and Future Directions]]>https://benthamscience.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[ACE2/Angiotensin-(1-7)/Mas Receptor Axis in Human Cancer: Potential Role for Pediatric Tumors]]>https://benthamscience.comarticle/104354Background: Pediatric tumors remain the highest cause of death in developed countries. Research on novel therapeutic strategies with lesser side effects is of utmost importance. In this scenario, the role of Renin-Angiotensin System (RAS) axes, the classical one formed by angiotensinconverting enzyme (ACE), Angiotensin II and AT1 receptor and the alternative axis composed by ACE2, Angiotensin-(1-7) and Mas receptor, have been investigated in cancer.

Objective: This review aimed to summarize the pathophysiological role of RAS in cancer, evidence for anti-tumor effects of ACE2/Angiotensin-(1-7)/Mas receptor axis and future therapeutic perspectives for pediatric cancer.

Methods: Pubmed, Scopus and Scielo were searched in regard to RAS molecules in human cancer and pediatric patients. The search terms were “RAS”, “ACE”, “Angiotensin-(1-7)”, “ACE2”, “Angiotensin II”, “AT1 receptor”, “Mas receptor”, “Pediatric”, “Cancer”.

Results: Experimental studies have shown that Angiotensin-(1-7) inhibits the growth of tumor cells and reduces local inflammation and angiogenesis in several types of cancer. Clinical trials with Angiotensin-( 1-7) or TXA127, a pharmaceutical grade formulation of the naturally occurring peptide, have reported promising findings, but not enough to recommend medical use in human cancer. In regard to pediatric cancer, only three articles that marginally investigated RAS components were found and none of them evaluated molecules of the alternative RAS axis.

Conclusion: Despite the potential applicability of Angiotensin-(1-7) in pediatric tumors, the role of this molecule was never tested. Further clinical trials are necessary, also including pediatric patients, to confirm safety and efficiency and to define therapeutic targets.

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<![CDATA[Trabectedin (Yondelis®) as a Therapeutic Option in Gynecological Cancers: A Focus on its Mechanisms of Action, Clinical Activity and Genomic Predictors of Drug Response]]>https://benthamscience.comarticle/104007 <![CDATA[Artemia species: An Important Tool to Screen General Toxicity Samples]]>https://benthamscience.comarticle/105658 <![CDATA[B7-H3-targeted Radioimmunotherapy of Human Cancer]]>https://benthamscience.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[Pisosterol Induces G2/M Cell Cycle Arrest and Apoptosis via the ATM/ATR Signaling Pathway in Human Glioma Cells]]>https://benthamscience.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[Single Nucleotide Polymorphism Analysis in HIV and Kaposi's Sarcoma Disease by Microarray Technique]]>https://benthamscience.comarticle/104088Background: Emergence of Kaposi's Sarcoma in the cases other than HIV, following the use of immunosuppressant drugs, demonstrates that it is related to weak immunity. The fact that this malignancy does not occur in every HIV-positive patient suggests that genetic predisposition may also be effective. Replacement of one of the base pairs of adenine, guanine, cytosine, and thymine that constitute the DNA sequence in the human genome with another base pair can affect susceptibility to disease, response to treatment, and immunity.

Objective: The purpose of this study is to analyze the Single Nucleotide Polymorphism that could predispose to Kaposi's sarcoma of an HIV-infected patient and to identify which nucleotides such SNPs correspond to, using the microarray technology.

Materials and Methods: The blood samples of individuals, one of whom was diagnosed with Kaposi's Sarcoma HIV (+) visiting the outpatient clinic of infectious diseases polyclinic of Harran University Research and Practice Hospital and of a healthy individual with no Kaposi's Sarcoma, were used in the study. Following the DNA isolation of the blood samples taken from the respective individuals, a SNP analysis was conducted on the microarray device. 204,000 SNPs obtained were scanned later on in the databases in an attempt to identify the SNPs related to Kaposi's Sarcoma.

Results: In the 204,000 SNP screenings, we scrutinized the SNPs that differ in the case of Kaposi's Sarcoma [KS (+) and HIV (+)] on the basis of Control [KS(-) and HIV(-)] and HIV+ [KS(-)], and two SNPs of the ENDRA gene, three SNPs of the ADRA1A gene, six SNPs of the STIM1 gene, four SNPs of the EFNB2 gene, and one SNP of the CD209 gene were found to be different. However, when it comes to all SNPs (all the 204.000 SNPs) screened in terms of allele, it was observed that the AA and BB alleles were lower in the patient with Kaposi's Sarcoma [KS (+) and HIV (+)] compared to other groups and AB alleles were found to be higher than others in the patient with Kaposi's sarcoma [KS] (+) and HIV (+)].

Conclusion: In the microarray study we have conducted, 204,000 SNPs were screened for Control (HIV-) HIV (+) and HIV (+) patient with Kaposi's Sarcoma. It was found that 32,362 of those SNPs had different alleles in the Kaposi's Sarcoma [KS + HIV (+)] patient, while they had the same ones in the control [KS (-) and HIV (-)] and HIV + [KS (-)] group. 16 of the 32,362 SNPs took place among the genes related to Kaposi's Sarcoma. In the cases of Kaposi's Sarcoma with suspected diagnosis, it can be used as a beneficial laboratory test.

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<![CDATA[Secretory Clusterin as a Novel Molecular-targeted Therapy for Inhibiting Hepatocellular Carcinoma Growth]]>https://benthamscience.comarticle/99186Background: Although secretory clusterin (sCLU) plays a crucial role in Hepatocellular Carcinoma (HCC) cells proliferation, Multiple Drug Resistance (MDR), metastasis and so on, its targeted effects and exact mechanism are still unknown. This review summarizes some new progress in sCLU as a molecular-targeted therapy in the treatment of HCC.

Methods: A systematic review of the published English-language literature about sCLU and HCC has been performed using the PubMed and bibliographic databases. Some valuable studies on sCLU in HCC progression were searched for relevant articles with the keywords: HCC, diagnosis, MDR, as molecular-targeted in treatment, and so on.

Results: The incidence of the positive rate of sCLU was significantly higher in HCC tissues as compared to the surrounding tissues at mRNA or protein level, gradually increasing with tumor-nodemetastasis staging (P<0.05). Also, the abnormal level of sCLU was related to poor differentiation degree, and considered as a useful marker for HCC diagnosis or independent prognosis for patients. Hepatic sCLU could be silenced at mRNA level by specific sCLU-shRNA or by OGX-011 to inhibit cancer cell proliferation with an increase in apoptosis, cell cycle arrest, reversal MDR, alteration of cell migration or invasion behaviors, and a decrease in GSK-3β or AKT phosphorylation in vitro, as well as significant suppression of the xenograft growth by down-regulating β-catenin, p-GSK3β, and cyclinD1 expression in vivo.

Conclusion: Abnormal hepatic sCLU expression should not only be a new diagnostic biomarker but also a novel promising target for inhibiting HCC growth.

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<![CDATA[Novel Homeodomain Transcription Factor Nkx2.2 in the Brain Tumor Development]]>https://benthamscience.comarticle/87675Background: Complex central nervous system (CNS) is made up of neuronal cells and glial cells. Cells of central nervous system are able to regenerate after injury and during repairing. Sonic hedgehog pathway initiated by Shh-N a glycoprotein plays vital role in CNS patterning growth, development and now tumorigenesis. Nkx2.2 homeodomain transcription factor is an effecter molecule, which is positively regulated by Shh during normal growth. Nkx2.2 is essential for V3 domain specification during neural tube patterning at embryonic stage. MBP + oligodendrocytes are differentiated from progenitor cells which express Olig2. Nx2.2 is co-expressed with Olig2 in oligodendrocytes and is essential for later stage of oligodendrocyte maturation.

Objective: This review paper explores the potential role of Nkx2.2 transcription factor in glioblastoma development.

Conclusion: Shh pathway plays a vital role in oligodendrocytes differentiation and Nkx2.2 transcription factor is essential for oligodendrocytes differentiation and maturation. Intriguingly, down regulation of Nkx2.2 transcription factor with aberrant Shh signaling pathway is reported in glioma samples. So here it is suggested that Nkx2.2 expression pattern could be used as a potential biomarker for the early diagnosis of glioma.

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<![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[Preclinical and Clinical Studies on Bryostatins, A Class of Marine-Derived Protein Kinase C Modulators: A Mini-Review]]>https://benthamscience.comarticle/105477 <![CDATA[Isoform-Selective PI3K Inhibitors for Various Diseases]]>https://benthamscience.comarticle/103500 <![CDATA[Determination of Dysregulated miRNA Expression Levels by qRT-PCR after the Application of Usnic Acid to Breast Cancer]]>https://benthamscience.comarticle/100969Background and Purpose: Breast cancer still remains to be one of the most threatening cancer types in women. Recent studies have allowed scientists to better investigate the potential use of natural compounds in the treatment of breast cancers. Usnic acid is a secondary metabolite extracted from lichen species and has many biological activities. The response of microRNAs regulated by drug molecules may provide useful diagnostic and prognostic biomarkers, as well as potential therapeutics for breast cancers. Although the aberrant expression of microRNAs was observed after drug treatment, the regulatory mechanisms remain partially known. Micro RNAs (miRNAs) play an important role in gene regulation at the post-transcriptional level.

Methods: In this study, we used quantitative Real-Time PCR (qRT-PCR) technology to demonstrate that usnic acid significantly changes the expression profile of miRNAs.

Results: Eleven miRNAs were significantly and differentially expressed in breast cancer cells after treatment with usnic acid. Three miRNAs were up-regulated, while eight were down-regulated in usnic acid treated cells. Target prediction and GO analysis revealed many target genes and their related pathways that are potentially regulated by usnic acid regulated differentially expressed miRNAs. We found that usnic acid treatment caused significant changes in the expression of hsa-miR-5006-5p, hsa-miR-892c-3p, hsa-miR-4430, hsa-miR-5194, hsa-miR-3198, hsa-miR-3171, hsa-miR-933 and hsa-miR-185-3p in breast cancer cells.

Conclusion: Usnic acid response miRNAs might play important regulatory roles in the tumorigenesis and development of breast cancer, and they could serve as prognostic predictors for breast cancer patients.

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<![CDATA[Thiosemicarbazones as Potent Anticancer Agents and their Modes of Action]]>https://benthamscience.comarticle/101991 <![CDATA[Studies on Structures and Functions of Kinases leading to Prostate Cancer and Their Inhibitors]]>https://benthamscience.comarticle/105459Background: Cancer is the uncontrolled growth of abnormal cells in any part of the body. These abnormalities in the cells make them cancer cells, malignant cells, or tumour cells. These cells can infiltrate normal body tissues. Prostate Cancer begins when cells in the prostate gland start to grow out of control.

Introduction: According to the National Cancer Institute, an estimated 20 percent of men experience Prostate Cancer in their lifetimes. Prostate Cancer can be divided into castration sensitive or hormone- sensitive Prostate Cancer (CSPC or HSPC) and castration-resistant Prostate Cancer (CRPC). Different therapies showed potential for the treatment of Prostate Cancer in that androgen receptor antagonist, cytochrome p17 inhibitors, radiation therapy, brachytherapy, surgical removal of the gland, androgen deprivation therapy and LnRH antagonists are some of the important ones. Despite various available treatment options in our understanding of the biological basis of Prostate Cancer, the management of the disease, especially in the castration-resistant phase, remains a significant challenge. Several Tyrosine kinase inhibitors (TKIs) have been evaluated in the preclinical setting in Advanced Prostate Cancer. TKIs are small drug molecules that work by competitive ATP inhibition at the catalytic binding site of tyrosine kinase. This results in complete inhibition of the catalytic activity of certain enzymes. If chosen correctly, TKIs can target and inhibit critical, mutated pathways important for the development, progression and metastasis of Prostate Cancer. The review focuses on various tyrosine kinase drug targets and their chemical structure to discuss the mechanism and pathways in the treatment of Prostate Cancer.

Methods: The method adopted for the study was mainly based on the secondary search through a systematic literature review. Targets discussed in this review include the epidermal growth factor family (EGFR), vascular endothelial growth factor family (VEGF) receptor, c-Src family kinases (Proto-oncogene tyrosine-protein kinase) (c-Src), platelet-derived growth factor (PDGF) and cmesenchymal- epithelial transition factor (c-Met), which showed some promising results in various studies.

Results: Even with the strong scientific rationale for many TKIs in the treatment of Prostate Cancer, the clinical trial experience showed some negative results in advanced phases. However, despite various challenges, the validation studies targeting kinases hold great potential in Prostate Cancer. Given the success of kinase inhibitors across multiple other cancer types, it is likely that this drug class will eventually improve outcomes in Prostate Cancer.

Conclusion: Modifications in structures and certain other aspects of TKIs may make these agents promising for the treatment of Prostate Cancer.

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<![CDATA[Lipid-based Nanoplatforms in Cancer Therapy: Recent Advances and Applications]]>https://benthamscience.comarticle/103666 <![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[Natural Products as a Paradigm for the Treatment of Coxsackievirus - induced Myocarditis]]>https://benthamscience.comarticle/104012 <![CDATA[The Effects of Dietary Supplements that Overactivate the Nrf2/ARE System]]>https://benthamscience.comarticle/98532

Methods: The literature on inflammation and the Nrf2/ARE antioxidant system was searched systematically. Articles from prestigious, peer-reviewed journals were obtained and read. The information obtained from them was used to write this review article.

Results: Over 150 articles and books were read. The information obtained from them showed that very few dietary antioxidants exert their effects by reacting directly with Reactive Oxygen and Nitrogen Species (RONS). Instead, most of the effective antioxidants activate the endogenous Nrf2/ARE antioxidant system. This helps prevent smoldering inflammation and the diseases that it can cause. However, when overactivated or activated constitutively, the Nrf2/ARE antioxidant system can cause some of these diseases, including many types of multidrug resistant cancer, autoimmune, neurodegenerative and cardiovascular diseases.

Conclusion: Even though green tea, as well as many fruits, vegetables and spices are quite healthy, dietary supplements that deliver much higher doses of antioxidants may not be. People who are diagnosed with cancer and plan to start chemotherapy and/or radiotherapy should probably avoid such supplements. This is because multidrug resistant tumors can hijack and overactivate the Nrf2/ARE antioxidant system.]]>
<![CDATA[Anticancer Potential of Dietary Natural Products: A Comprehensive Review]]>https://benthamscience.comarticle/101453 <![CDATA[Bioactive Secondary Metabolites from Endophytic Fungi]]>https://benthamscience.comarticle/100825

Objective: The present review provides an overview of secondary metabolites from endophytic fungi with pronounced biological activities covering the literature between 2010 and 2017. Special focus is given on studies aiming at exploration of the mode of action of these metabolites towards the discovery of leads from endophytic fungi. Moreover, this review critically evaluates the potential of endophytic fungi as alternative sources of bioactive “plant metabolites”.

Results: Over the past few years, several promising lead structures from endophytic fungi have been described in the literature. In this review, 65 metabolites are outlined with pronounced biological activities, primarily as antimicrobial and cytotoxic agents. Some of these metabolites have shown to be highly selective or to possess novel mechanisms of action, which hold great promises as potential drug candidates.

Conclusion: Endophytes represent an inexhaustible reservoir of pharmacologically important compounds. Moreover, endophytic fungi could be exploited for the sustainable production of bioactive “plant metabolites” in the future. Towards this aim, further insights into the dynamic endophyte - host plant interactions and origin of endophytic fungal genes would be of utmost importance.]]>
<![CDATA[Anthocyanins As Modulators of Cell Redox-Dependent Pathways in Non-Communicable Diseases]]>https://benthamscience.comarticle/94419Chronic Noncommunicable Diseases (NCDs), mostly represented by cardiovascular diseases, diabetes, chronic pulmonary diseases, cancers, and several chronic pathologies, are one of the main causes of morbidity and mortality, and are mainly related to the occurrence of metabolic risk factors. Anthocyanins (ACNs) possess a wide spectrum of biological activities, such as anti-inflammatory, antioxidant, cardioprotective and chemopreventive properties, which are able to promote human health. Although ACNs present an apparent low bioavailability, their metabolites may play an important role in the in vivo protective effects observed.

This article directly addresses the scientific evidences supporting that ACNs could be useful to protect human population against several NCDs not only acting as antioxidant but through their capability to modulate cell redox-dependent signaling. In particular, ACNs interact with the NF-κB and AP-1 signal transduction pathways, which respond to oxidative signals and mediate a proinflammatory effect, and the Nrf2/ARE pathway and its regulated cytoprotective proteins (GST, NQO, HO-1, etc.), involved in both cellular antioxidant defenses and elimination/inactivation of toxic compounds, so countering the alterations caused by conditions of chemical/oxidative stress. In addition, supposed crosstalks could contribute to explain the protective effects of ACNs in different pathological conditions characterized by an altered balance among these pathways. Thus, this review underlines the importance of specific nutritional molecules for human health and focuses on the molecular targets and the underlying mechanisms of ACNs against various diseases.

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<![CDATA[Vesicle Trafficking, Autophagy and Nanoparticles: A Brief Review]]>https://benthamscience.comarticle/100678Background: Nanomedicine shows a huge promise for incurable diseases. So far, more than 50 nanoparticles have been approved by FDA and around 80 nanoformulations are currently in clinical trials. Nanoparticles possess several advantages over traditional drugs, including higher biocompatibility and bioavailability. One of the challenges for their wide application is insufficient understanding of the molecular network related to internalization of particles and intracellular release of cargos.

Objective: This article aims to review the interactions between nanoparticles, vesicle transportation and autophagy pathways. The underlying molecular machinery is also discussed.

Methods: For each step of the vesicle trafficking and autophagy, details of signaling pathways are described for a better understanding of the interactions between delivery vehicles and biomolecules within the cell.

Conclusion: The selection of cellular uptake route mainly depends on physical characteristics of nanoparticles. For nanoparticles modified with ligands, they undergo receptormediated endocytic pathway. Once residing within the cells, cargos are released after disruption of endosomes, a mechanism called ‘proton sponge effect’. Besides, internalized nanoparticles either can be exocytosized, or they initiate the autophagy response, affecting the intracellular distribution of drugs.

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<![CDATA[Melatonin Induces Apoptosis and Inhibits the Proliferation of Cancer Cells via Reactive Oxygen Species-mediated MAPK and mTOR Pathways]]>https://benthamscience.comarticle/102415Background: Recent human and animal studies have demonstrated the oncostatic properties of N-acetyl-5-methoxytryptamine (melatonin) in different types of cancer. However, in few cancer cell lines including colorectal cancer cell line (HT-29), acute T cell leukemia cell line (JURKAT) and cervical cancer cell line (HeLa), precise oncostatic mechanism induced by melatonin is yet to be described.

Objectives: The aim of this study is to investigate the effects of melatonin in HT-29, JURKAT and HeLa cells and to determine the underlying molecular mechanism.

Methods: Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay while cell cycle, apoptosis and membrane potential were analysed by flow cytometry. Reactive oxygen species (ROS) was detected by 2',7'-dichlorofluorescein diacetate (DCFH-DA) staining. Protein expressions were determined by Western blot.

Results: Our results showed that melatonin suppressed cell proliferation, increased the number of sub G1 hypodiploid cells and cell cycle arrest in HT-29, JURKAT and HeLa cells. Besides, melatonin also induced early and late apoptosis, although there were marked variations in responses between different cell lines (sensitivity; HeLa > HT-29 >JURKAT). Apart from that, staining with DCHF-DA demonstrated ROS production that was induced in a dose-dependent manner in HeLa, HT-29 and JURKAT cells. Moreover, the apoptotic process and oncostatic effect of melatonin were seen to be associated with extracellular-signal-regulated kinase (ERK) and stress-activated protein kinase/c-Jun NH (2)-terminal kinase (SAPK-JNK) signalling cascades in HeLa cells. In HT-29 and JURKAT cells, melatonin induced apoptosis via activation of p38 mitogen-activated protein kinases (p38), ERK and SAPK-JNK signalling pathways. In all three cell lines, the apoptotic event was triggered by the mammalian target of rapamycin (mTOR)-mediated activation of the downstream target rapamycininsensitive companion of mTOR (RICTOR) and/or regulatory-associated protein of mTOR (RAPTOR) proteins.

Conclusion: Our findings confirm that melatonin induces apoptosis through reactive oxygen speciesmediated dysregulated mitogen-activated protein kinase (MAPK) and mTOR signalling pathways in these cancer cell lines.

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<![CDATA[Antiviral Activities of Human Host Defense Peptides]]>https://benthamscience.comarticle/100131 <![CDATA[Immunotherapy for Uveal Melanoma - Current Knowledge and Perspectives]]>https://benthamscience.comarticle/99400 <![CDATA[An HHV-8 Positive HIV Negative Multicentric Castleman’s Disease, who Responded well to Rituximab Alone]]>https://benthamscience.comarticle/96905Background: Multicentric Castleman Disease (MCD) presents with enlarged lymph nodes in multiple regions and systemic inflammatory symptoms, due to the dysregulation of cytokines, most commonly interleukin-6 (IL-6). Human herpes virus-8 (HHV-8) is strongly related to MCD (HHV-8-associated MCD) and is being implicated in cytokine dysregulation in patients, the majority of whom are HIV positive or immunosuppressed. Preferred treatment of HHV-8- associated MCD depends on the presence or not of concurrent Kaposi sarcoma and on whether the patient has life-threatening organ failure or poor performance status thought to be related to HHV- 8-associated MCD.

Case Presentation: Herein, we describe a female patient with HHV-8 positive, HIV negative MCD, who responded well to the administration of rituximab once weekly for four weeks alone for three cycles.

Conclusion: HHV-8 positive, HIV negative MCD treatment modalities are only anecdotal due to the rarity of this form of MCD. Administration of rituximab alone seems to be beneficial among patients with good performance status and the absence of life-threatening organ failure in cases of HHV-8 positive, HIV negative MCD.

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<![CDATA[Recent Advances in the Discovery of Novel HSP90 Inhibitors: An Update from 2014]]>https://benthamscience.comarticle/100528 <![CDATA[Hotspot Mutations in DICER1 Causing GLOW Syndrome-Associated Macrocephaly <i>via</i> Modulation of Specific microRNA Populations Result in the Activation of PI3K/ATK/mTOR Signaling]]>https://benthamscience.comarticle/99175Background: We have previously described mosaic mutations in the RNase IIIb domain of DICER1that display global developmental delays, lung cysts, somatic overgrowth, macrocephaly and Wilms tumor. This constellation of phenotypes was classified as GLOW syndrome. Due to the phenotypic overlap between GLOW and syndromes caused by mutations in the PI3K/AKT/mTOR pathway, we hypothesized that alterations in miRNA regulation of this pathway cause its specific constellation of phenotypes.

Objective: To test the hypothesis that DICER1 “hot spot” mutations associated with GLOW syndrome activate PI3K/AKT/mTOR signaling.

Methods: We developed HEK293T cells with loss of exon 25 in DICER1, a genetic modification that is synonymous with the “hot spot” RNAseIIIb mutations that cause GLOW syndrome. We assayed the cells for activation of the PI3K/AKT/mTOR signaling pathway.

Results: We observed activation of the PI3K/AKT/mTOR pathway as demonstrated by increased pS6Kinase, p4EBP1 and pTSC2 levels. Additionally, these cells demonstrate a striking cellular phenotype, with the ability to form spheres when the serum is removed from their growth medium. The cells in these spheres are Oct4 and Sox2 positive and exhibit the property of reversion with the addition of serum. We queried miRNA expression data and identified a population of miRNAs that increase due to these mutations and target negative regulators of the PI3K/AKT/mTOR pathway.

Conclusion: This work identifies the delicate and essential role for miRNA control of the PI3K/AKT/mTOR pathway. We conclude that the phenotypes observed in the GLOW syndrome are the result of PI3K/AKT/mTOR activation.

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<![CDATA[Interaction of Human Herpesvirus 8 Viral Interleukin-6 with Human Interleukin-6 Receptor Using <i>In Silico</i> Approach: The Potential Role in HHV-8 Pathogenesis]]>https://benthamscience.comarticle/99236Introduction: Human Herpesvirus 8 (HHV-8) causes classical, endemic (African), and Acquired Immunodeficiency Syndrome (AIDS)-related Kaposi’s Sarcoma (KS), Body Cavity-Based Primary Effusion Lymphomas (BCBL), HHV-8-associated peritoneal Primary Effusion Lymphoma (PEL), and Multicentric Castleman’s Disease (MCD). HHV8 genome encodes several structural and non-structural proteins, among which vIL6 is a functional homologue of Interleukin-6 (IL-6). It has been established that vIL6 plays a vital role in HHV8 infections; also, it has been suggested that its function was mediated through gp130, rather than the gp80 (IL-6 receptor [IL-6R]). This study aimed to investigate the physicochemical and structural properties as well as the immunological features, and finally the interaction between vIL6 and IL6 receptor (IL6R) by using several bioinformatics tools which could provide both valuable insight into vIL6 protein and advantageous data for further studies on HHV8 inhibitors and new vaccines.

Material and Methods: vIL6, human IL6 (hIL6), and IL6R were obtained from NCBI GenBank and Uniport, which were aligned by The CLC Genomics Workbench. "Signal-BLAST" and “predisi" were employed to define signal peptide; also, “Expasy’sProtParam” was used to predict physicochemical properties as well as "DiANNA", and "SCRATCH" predicted the disulfide bonds. “NetPhosK”, “DISPHOS”, “NetPhos”, ”NetNGlyc”, and ”GlycoEP” were involved to determine post-modification sites. To define immunoinformatics analysis, “BcePred”, “ABCpred”, “Bepipred”, “AlgPred”, and "VaxiJen" were used. “SOPMA”, “I-TASSER”, “GalaxyRefine”, and “3D-Refine” predicted and refined the secondary and tertiary structures. TM-align server was used to align 3D structures. In addition, docking analysis was done by “Hex 5.0.”, and finally the results were illustrated by “Discovery Studio”.

Results: A signal peptide (1-22) was defined in the vIL6 sequences and analysis has shown that vIL6 is an acidic protein which is significantly stable in all organisms. Three Disulfide bonds were predicted and immunoinformatics analysis showed 5 distinct B-cell epitopes. vIL6 is predicted as a non-allergen protein and the majority of its structure consists of Alpha helix. TM-align pointed the significant similarity between vIL6 and hIL6 in protein folding. The high energy value between vIL6 protein and IL6R was calculated and further analysis illustrated 5 conserved regions as well as 4 conserved amino acids which had a significant role in vIL6 and IL6R interaction.

Discussion: An in silico study by numerous software determined the possible interaction between vIL6 and IL6R and the possible role of this interaction in HHV8 pathogenesis and the progress of infection. These have been overlooked by previous studies and will be beneficial to gain a more comprehensive understanding of vIL6 function during HHV8 lifecycle and infections. Structural analysis showed the significant similarity between vIL6 and hIL6 folding which can describe the similarity of the functions or interactions of both proteins. Furthermore, several conserved regions in the interaction site which interestingly were highly conserved among all vIL6 sequences can be used as new target for vIL6 inhibitors. Moreover, our results could predict immunological properties of vIL6 which suggested the ability of this protein in induction of the humoral immune response. Such a protein may be used for further studies on therapeutic vaccine fields.

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<![CDATA[Synthesis of Substituted Cinnamido Linked Quinazolinone Congeners as Potential Anticancer Agents via Mitochondrial Dependent Intrinsic Apoptotic Pathway]]>https://benthamscience.comarticle/100709Background: The synthesis of novel heterocyclic scaffolds with amide functionality is a key research area due to their plethora of medicinal applications. The present study aims to explore the synthesis of new cinnamido linked quinazolinone congeners and their potential as anticancer agents.

Methods: Cytotoxicity evaluation, Cell cycle analysis, JC-1 staining, ROS, Annexin V assays, AO/EB, DAPI nuclear staining, Colony-forming assay and Western blot analysis.

Results: Among the synthesized compounds, 5eb and 5fc have shown promising cytotoxic activity with an IC50 value of 3.89±1.01µM and 4.05±0.62µM against HeLa cell lines. The flow-cytometry analysis demonstrated that the compound 5eb arrested the sub-G1 phase of the cell cycle and induced apoptosis. Furthermore, the compound 5eb triggered the collapse of mitochondrial membrane potential (ΔΨm), which was assessed by JC-1 staining and also induced the generation of Reactive Oxygen Species. An increase in the expression of proapoptotic proteins such as Bax, p53, cleaved PARP and cleaved caspase-3 by 5eb confirmed the activation of the mitochondrial-dependent intrinsic apoptosis pathway.

Conclusion: Our results suggest that compound 5eb and 5fc of cinnamido linked quinazolinone derivatives could serve as potential leads in the development of novel chemotherapeutic agents.

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<![CDATA[Advances in the Treatment of Ovarian Cancer Using PARP Inhibitors and the Underlying Mechanism of Resistance]]>https://benthamscience.comarticle/100997 <![CDATA[Vulvar Leiomyomatosis: A Diagnostic Challenge Case Report]]>https://benthamscience.comarticle/96181Introduction: Vulvar leiomyomas are rare and usually misdiagnosed as Bartholin’s cyst on initial presentation. Leiomyoma of vulva accounts for only 0.03% of all gynecological neoplasm. Definite diagnosis is based on surgical excision of the tumor. The aim of this report is to introduce a case of leiomyoma of the vulva which was initially misdiagnosed as Bartholin’s cyst.

Case Presentation: We present a case of a 36-year old virgin female (BMI>30) who was referred to the clinic with a 5-year history of left labial mass which was initially diagnosed as Bartholin’s cyst. The mass was removed and the pathologist confirmed that the final diagnosis was vulvar leiomyoma.

Conclusion: Vulvar leiomyoma is usually misdiagnosed with Bartholin cyst and distinguishing between benign and malignant forms is confusing, so it is a diagnostic challenge. Surgical excision is the treatment of choice in all smooth muscle tumors of the vulva. Continuing follow-up after treatment is highly recommended.

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<![CDATA[The Chemical Methods of Disulfide Bond Formation and Their Applications to Drug Conjugates]]>https://benthamscience.comarticle/102690 <![CDATA[An Overview on Pyranocoumarins: Synthesis and Biological Activities]]>https://benthamscience.comarticle/101911 <![CDATA[Transition Metal-Based Prodrugs for Anticancer Drug Delivery]]>https://benthamscience.comarticle/94975 <![CDATA[Zinc Dependent Histone Deacetylase Inhibitors in Cancer Therapeutics: Recent Update]]>https://benthamscience.comarticle/90775Background: Histone deacetylases (HDAC) are an important class of enzymes that play a pivotal role in epigenetic regulation of gene expression that modifies the terminal of core histones leading to remodelling of chromatin topology and thereby controlling gene expression. HDAC inhibitors (HDACi) counter this action and can result in hyperacetylation of histones, thereby inducing an array of cellular consequences such as activation of apoptotic pathways, generation of reactive oxygen species (ROS), cell cycle arrest and autophagy. Hence, there is a growing interest in the potential clinical use of HDAC inhibitors as a new class of targeted cancer therapeutics.

Methodology and Result: Several research articles spanning between 2016 and 2017 were reviewed in this article and presently offer critical insights into the important strategies such as structure-based rational drug design, multi-parameter lead optimization methodologies, relevant SAR studies and biology of various class of HDAC inhibitors, such as hydroxamic acids, benzamides, cyclic peptides, aliphatic acids, summarising the clinical trials and results of various combination drug therapy till date.

Conclusion: This review will provide a platform to the synthetic chemists and biologists to cater the needs of both molecular targeted therapy and combination drug therapy to design and synthesize safe and selective HDAC inhibitors in cancer therapeutics.

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<![CDATA[Possible Pathways of Hepatotoxicity Caused by Chemical Agents]]>https://benthamscience.comarticle/102099Background: Liver injury induced by drugs has become a primary reason for acute liver disease and therefore posed a potential regulatory and clinical challenge over the past few decades and has gained much attention. It also remains the most common cause of failure of drugs during clinical trials. In 50% of all acute liver failure cases, drug-induced hepatoxicity is the primary factor and 5% of all hospital admissions.

Methods: The various hepatotoxins used to induce hepatotoxicity in experimental animals include paracetamol, CCl4, isoniazid, thioacetamide, erythromycin, diclofenac, alcohol, etc. Among the various models used to induce hepatotoxicity in rats, every hepatotoxin causes toxicity by different mechanisms.

Results: The drug-induced hepatotoxicity caused by paracetamol accounts for 39% of the cases and 13% hepatotoxicity is triggered by other hepatotoxic inducing agents.

Conclusion: Research carried out and the published papers revealed that hepatotoxins such as paracetamol and carbon- tetrachloride are widely used for experimental induction of hepatotoxicity in rats.

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<![CDATA[The Role of Shcbp1 in Signaling and Disease]]>https://benthamscience.comarticle/99102 <![CDATA[Distribution and Characteristics of Intrathoracic Lymphadenopathy in TB/HIV Co-Infection]]>https://benthamscience.comarticle/93708Background: Intrathoracic Lymphadenopathy (ITLN) in Human Immunodeficiency Virus (HIV) infected patients may have various etiologies and prognoses. Etiologies of ITLN can be distinguished based on the distribution of enlarged lymph nodes. Sometimes tuberculosis (TB) is the first sign of underlying HIV infection.

Objectives: We sought to determine ITLN distribution and associated pulmonary findings in TB/HIV co-infection using Computed Tomography (CT) scan.

Methods: In this retrospective, observational, cross-sectional study, chest CT scans of 52 patients with TB/HIV co-infection were assessed for enlarged intrathoracic lymph nodes (>10 mm in short axis diameter), lymphadenopathy (LAP) distribution, calcification, conglomeration, the presence of hypodense center and associated pulmonary abnormalities. LAP distribution was compared in TB/HIV co-infection with isolated TB infection.

Results: Mediastinal and/or hilar LAP were seen in 53.8% of TB/HIV co-infection patients. In all cases, LAP was multistational. The most frequent stations were right lower paratracheal and subcarinal stations. Lymph node conglomeration, hypodense center and calcification were noted in 25%, 21.4% and 3.5% of patients, respectively. LAP distribution was the same as that in patients with isolated TB infection except for the right hilar, right upper paratracheal and prevascular stations. All patients with mediastinal and/or hilar adenopathy had associated pulmonary abnormalities.

Conclusion: All patients with TB/HIV co-infection and mediastinal and/or hilar adenopathy had associated pulmonary abnormalities. Superior mediastinal lymph nodes were less commonly affected in TB/HIV co-infection than isolated TB.

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<![CDATA[Structural and Mechanistic Insights of CRAC Channel as a Drug Target in Autoimmune Disorder]]>https://benthamscience.comarticle/101039Background: Calcium (Ca2+) ion is a major intracellular signaling messenger, controlling a diverse array of cellular functions like gene expression, secretion, cell growth, proliferation, and apoptosis. The major mechanism controlling this Ca2+ homeostasis is store-operated Ca2+ release-activated Ca2+ (CRAC) channels. CRAC channels are integral membrane protein majorly constituted via two proteins, the stromal interaction molecule (STIM) and ORAI. Following Ca2+ depletion in the Endoplasmic reticulum (ER) store, STIM1 interacts with ORAI1 and leads to the opening of the CRAC channel gate and consequently allows the influx of Ca2+ ions. A plethora of studies report that aberrant CRAC channel activity due to Loss- or gain-of-function mutations in ORAI1 and STIM1 disturbs this Ca2+ homeostasis and causes several autoimmune disorders. Hence, it clearly indicates that the therapeutic target of CRAC channels provides the space for a new approach to treat autoimmune disorders.

Objective: This review aims to provide the key structural and mechanical insights of STIM1, ORAI1 and other molecular modulators involved in CRAC channel regulation.

Results and Conclusion: Understanding the structure and function of the protein is the foremost step towards improving the effective target specificity by limiting their potential side effects. Herein, the review mainly focusses on the structural underpinnings of the CRAC channel gating mechanism along with its biophysical properties that would provide the solid foundation to aid the development of novel targeted drugs for an autoimmune disorder. Finally, the immune deficiencies caused due to mutations in CRAC channel and currently used pharmacological blockers with their limitation are briefly summarized.

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<![CDATA[Mutational Testing in Gastrointestinal Stromal Tumor]]>https://benthamscience.comarticle/97547 <![CDATA[Study of HIV Resistance Mutations Against Antiretrovirals using Bioinformatics Tools]]>https://benthamscience.comarticle/101658Background: Antiretroviral drugs to HIV-1 (ARV) are divided into classes: Nucleotide Reverse Transcriptase Inhibitors (NRTIs); Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs); Protease Inhibitors (PIs); Integrase Inhibitors (INIs); fusion inhibitors and entry Inhibitors. The occurrence of mutations developing resistance to antiretroviral drugs used in HIV treatment take place in a considerable proportion and has accumulated over its long period of therapy.

Objective: This study aimed to identify resistance mutations to antiretrovirals used in the treatment of HIV-1 in strains isolated from Brazilian territory deposited at Genbank, as well as to relate to the clinical significance and mechanism of action.

Methods: Elucidation of these mutations was by comparative method of peptide sequence resulting from genes encoding therapeutic targets in HIV antiretroviral therapy (ART) of the strains with a reference sequence through bioinformatic genetic information manipulation techniques.

Results: Of the 399 sequences analyzed, 121 (30.3%) had some type of mutations associated with resistance to some class of antiretroviral drug. Resistance to NNRTIs was the most prevalent, detected in 77 (63.6%) of the 121 mutated sequences, compared to NRTIs and PIs, whose resistance was detected in 60 (49.6%) and 21 (17.3%), respectively, and to INIs, only 1 (0.8%) sample showed associated resistance mutation.

Conclusion: Resistance to HIV ARV was detected at a considerable rate of 30.3%, showing some concerns about the percentage of viral strains that escape the established therapeutic regimen and that circulate currently in Brazil. The non-use of NNRTIs in Brazil is justified by the emergence of resistance mutations. The low prevalence of mutations against INIs is because drugs in this class have a high genetic barrier.

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<![CDATA[Diagnostic Capabilities of MRI Versus 18F FDG PET-CT in Postoperative Patients with Thyroglobulin Positive, 131I-negative Local Recurrent or Metastatic Thyroid Cancer]]>https://benthamscience.comarticle/91793Background: The detection of recurrence or metastasis might be challenging in patients, who underwent total thyroidectomy and radioactive iodine therapy for Differentiated Thyroid Carcinoma (DTC), with increased serum Thyroglobulin (Tg) levels and negative 131I whole body scan (131I-WBS) results.

Aims: The purpose of this study was to compare the ability of Magnetic Resonance Imaging (MRI) and 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F FDG PET-CT) to detect recurrence or cervical and upper mediastinal metastases in postoperative DTC patients who had negative 131I-WBS despite elevated serum Tg levels.

Study Design: This study has a retrospective study design.

Methods: We evaluated cervical and upper mediastinal MRI and 18F FDG PET-CT of 32 postoperative patients with DTC (26 patients with papillary thyroid carcinoma and 6 patients with follicular thyroid carcinoma).

Results: We evaluated 44 lesions in 32 patients. For all lesions, the Positive Predictive Value, (PPV) Negative Predictive Value (NPV), sensitivity, specificity, and accuracy of MRI were 81.4%, 76.4%, 84.6%, 72.2%, and 79.5% respectively. The PPV, NPV, sensitivity, specificity, and accuracy of 18F FDG PET-CT were 100.0%, 85.7%, 88.4%, 100.0%, and 93.1%, respectively.

Conclusion: Although we could not replace 18F FDG PET-CT, MRI might be used as an adjunct to 18F FDG PET-CT for the evaluation of recurrent or cervical and upper mediastinal metastatic thyroid cancers; however, MRI is inadequate for the detection of metastases in small lymph nodes.

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<![CDATA[Anti-angiogenic Treatment in Metastatic Colorectal Cancer: Current Issues and Future Aims]]>https://benthamscience.comarticle/94641 <![CDATA[Immunology Behind Tumors: A Mini Review]]>https://benthamscience.comarticle/92872

Conclusion: This review is focused not only on the mechanism by which the immune system protects us but also on the ways in which it can inflict the body and how to modulate it with therapy. Thus, understanding the interaction of a tumor with the immune system provides insights into mechanisms that can be utilized to elicit anti-tumor immune responses. Here, we have recapitulated the function of the tumor microenvironment and immune checkpoints.

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<![CDATA[Crocins: The Active Constituents of Crocus Sativus L. Stigmas, Exert Significant Cytotoxicity on Tumor Cells In Vitro]]>https://benthamscience.comarticle/94063

Objectives: In this study, we focused on the anticancer potency of crocins, the main constituents of Crocus sativus L, stigmas. Crocins were first extracted using organic solvents from the dried stigmas and then were identified using the HPLC analysis.

Materials and Methods: TE-671 cells were treated with the extract of crocins using a range of concentrations between 0.25-mg/ mL and 16 mg/mL. Viability of the cells was measured at 24h, 48h, 72h and 96h. In addition, we have examined the expression levels of the p53 gene using Real-Time Reverse Transcription PCR.

Results: Results showed that crocins exerted significant cytotoxic and anti-proliferative effects in a concentration and time - dependent-manner on TE-671 cells. Furthermore, p53 manifested similar expression pattern as the anti-proliferative effect of crocin.

Conclusion: Our data demonstrate that crocins could be a novel promising agent for the improvement of tumor treatment.

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<![CDATA[Crocetin as an Active Secondary Metabolite of Saffron Stigma and Anticancer Effects]]>https://benthamscience.comarticle/91274 <![CDATA[Overview of Current Immunotherapies Targeting Mutated KRAS Cancers]]>https://benthamscience.comarticle/100650 <![CDATA[The Application of the RNA Interference Technologies for KRAS: Current Status, Future Perspective and Associated Challenges]]>https://benthamscience.comarticle/100507 <![CDATA[KRAS: A Promising Therapeutic Target for Cancer Treatment]]>https://benthamscience.comarticle/100667 <![CDATA[Kirsten Rat Sarcoma Viral Oncogene Homologue (KRAS) Mutations in the Occurrence and Treatment of Pancreatic Cancer]]>https://benthamscience.comarticle/100504 <![CDATA[Drug Combinatorial Therapies for the Treatment of KRAS Mutated Lung Cancers]]>https://benthamscience.comarticle/100587 <![CDATA[Recent Advances in Developing K-Ras Plasma Membrane Localization Inhibitors]]>https://benthamscience.comarticle/100586 <![CDATA[Targeting Protein Kinase Inhibitors with Traditional Chinese Medicine]]>https://benthamscience.comarticle/100115 <![CDATA[A Novel Highly Selective Cannabinoid CB2 Agonist Reduces in vitro Growth and TGF-beta Release of Human Glial Cell Tumors]]>https://benthamscience.comarticle/100965

Aims: To test the in vitro antitumor activity of COR167, a novel cannabinoid CB2-selective agonist displaying a high binding affinity for human CB2 receptors, on tumor cells isolated from human glioblastoma multiforme and anaplastic astrocytoma.

Methods: Glioma cell cultures were established from two glioblastoma multiforme and two anaplastic astrocytomas. Proliferation was measured in the presence or absence of COR167 with a bromodeoxyuridine (BrdU) cell proliferation ELISA assay. CB2 receptor expression was detected by western blotting. Apoptosis was assessed with phycoerythrin (PE) annexin V flow cytometry kit. TGF-beta 1 and 2 levels were analyzed in culture supernatants with commercial ELISAs.

Results: COR167 was found to significantly reduce the proliferation of both glioblastoma and anaplastic astrocytoma in a dose-dependent manner at lower doses than other known, less specific CB2 agonists. This activity is independent of apoptosis and is associated with a significant reduction of TGF-beta 1 and 2 levels in supernatants of glioma cell cultures.

Conclusion: These findings add to the role of cannabinoid CB2 receptor as a possible pharmacological target to counteract glial tumor growth and encourage further work to explore any other pharmacological effect of this novel CB2 agonist useful in the treatment of human gliomas.]]>
<![CDATA[Accessing the Blood-Brain Barrier to Treat Brain Disorders]]>https://benthamscience.comarticle/100440 <![CDATA[Targeting Protein-Protein Interaction with Covalent Small-Molecule Inhibitors]]>https://benthamscience.comarticle/101390 <![CDATA[An Overview of the Chemistry and Pharmacological Potentials of Furanones Skeletons]]>https://benthamscience.comarticle/100338 <![CDATA[The Molecular Pathology of Eye Tumors: A 2019 Update Main Interests for Routine Clinical Practice]]>https://benthamscience.comarticle/99994 <![CDATA[Meet Our Editorial Board Member]]>https://benthamscience.comarticle/101316 <![CDATA[Surface Modification: Approaches and Utilities]]>https://benthamscience.comarticle/100393Surface modification is the modification of the surface (either of carrier, drug or targeting moiety) by which solubility, opsonization, adhesion, longer circulation, and bioconjugation of an object can be achieved.

Techniques which modify surface properties of carriers, drugs, ligands, excipients, coating materials, etc. by introducing random, non-specific groups or selected, specific groups can be used to alter the surface properties of the object. Through this review, a small attempt is made to understand the surface modification techniques. In this review, several methods (surface modification by solid dispersion technique, surfactants, polaxamer and polaxamine coating, PEG (polyethylene glycol), Vitamin E, Dextran derivatives, Chitosan coating, chemicals, gas and through layer by layer techniques) are discussed for surface modification. A concise review was done to explore the availability of techniques and agents available to introduce a specific group into the object.

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<![CDATA[Novel Molecular Targets and Mechanisms Involved in the Invasion and Metastasis of Pancreatic Cancer]]>https://benthamscience.comarticle/97624Background: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancerrelated deaths and its morbidity and mortality are increasing. PDAC patients have a very poor prognosis because of aggressive features of PDAC cells, shortage of reliable diagnostic biomarkers and deficiency of effective therapeutics.

Objective: The article aims to discuss the recent progress in the discovery of novel molecular targets and their related mechanisms in the invasion and metastasis of PDAC cells.

Methods: Literatures based on Pubmed database were searched and those related to the molecular targets involved in the invasion and metastasis of PDAC were reviewed.

Results: The most promising discovery of molecular targets and phenomena include epithelialmesenchymal transition (EMT), cancer stem cells (CSCs), metastasis-related genes, hypoxiainducible factors (HIFs), non-coding RNAs (ncRNAs) and L1 cell adhesion molecule (L1CAM), which contribute to the vital biological behaviors of PDAC cells and tumor microenvironments.

Conclusion: This review summarizes recent advances in novel molecular targets that regulate the invasion and metastasis of PDAC cells, and how they are targeted for developing diagnostic and therapeutic tools for combating PDAC. Further understanding the regulatory mechanisms of these molecular targets may help to discover biomarkers used for early diagnosis, predicting the prognosis and monitoring treatment response, and also to develop novel effective therapeutics.

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<![CDATA[The Therapeutic Potential of Small Activating RNAs for Colorectal Carcinoma]]>https://benthamscience.comarticle/99453 <![CDATA[Primary Cardiac Tumors: A Retrospective Study]]>https://benthamscience.comarticle/98308Objectives: Primary cardiac tumors are rare and account for 0.001 to 0.03% of cardiac lesions. The authors aim to describe the clinical, the microscopic and the therapeutic characteristics of these tumors through a 13-year-experience in order to highlight the diagnostic challenges faced.

Methods: We report 10 primary cardiac tumors diagnosed in the Departments of Pathology and Thoracic Surgery of the same hospital through a 13-year-period.

Results: Our study was conducted on 7 women and 3 men. The mean age of the patients was 54.22 years (average, 12 to 79 years). Dyspnea represented the most frequent symptom. Physical examination was normal in all patients. Trans-thoracic ultra-sound examination was performed in all patients. Cardiac MRI allowed localizing the tumors in 2 patients. They were located into the left auricle (6 cases), the right auricle (1 case) and the pericardium (3 cases). The microscopic examination was concluded to myxoma (7 cases), haemangioma (2 cases) and hemangioendothelioma (1 case). Surgical resection was possible in 9 patients. It was impossible in the case of hemangioendothelioma because of the adherence. One death was recorded secondary to postoperative arrhythmia. The other patients presented no complications after a follow-up period ranging from 2 months to 5 years.

Conclusion: Cardiac tumors are challenging in their diagnosis and management. A positive diagnosis is based on microscopic examination. Surgical treatment plays a key role and is possible in the majority of benign tumors. The prognosis of malignant tumors remains poor even if a complete surgical resection is possible.

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<![CDATA[Molecular Mechanisms and Targeted Therapies Including Immunotherapy for Non-Small Cell Lung Cancer]]>https://benthamscience.comarticle/95116 <![CDATA[Nanoparticles: Properties and Applications in Cancer Immunotherapy ]]>https://benthamscience.comarticle/99481Background: Tumours are no longer regarded as isolated masses of aberrantly proliferating epithelial cells. Rather, their properties depend on complex interactions between epithelial cancer cells and the surrounding stromal compartment within the tumour microenvironment. In particular, leukocyte infiltration plays a role in controlling tumour development and is now considered one of the hallmarks of cancer. Thus, in the last few years, immunotherapy has become a promising strategy to fight cancer, as its goal is to reprogram or activate antitumour immunity to kill tumour cells, without damaging the normal cells and provide long-lasting results where other therapies fail. However, the immune-related adverse events due to the low specificity in tumour cell targeting, strongly limit immunotherapy efficacy. In this regard, nanomedicine offers a platform for the delivery of different immunotherapeutic agents specifically to the tumour site, thus increasing efficacy and reducing toxicity. Indeed, playing with different material types, several nanoparticles can be formulated with different shape, charge, size and surface chemical modifications making them the most promising platform for biomedical applications.

Aim: In this review, we will summarize the different types of cancer immunotherapy currently in clinical trials or already approved for cancer treatment. Then, we will focus on the most recent promising strategies to deliver immunotherapies directly to the tumour site using nanoparticles.

Conclusion: Nanomedicine seems to be a promising approach to improve the efficacy of cancer immunotherapy. However, additional investigations are needed to minimize the variables in the production processes in order to make nanoparticles suitable for clinical use.

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<![CDATA[Research Progress of Axl Inhibitors]]>https://benthamscience.comarticle/99131 <![CDATA[STAT3: A Potential Drug Target for Tumor and Inflammation]]>https://benthamscience.comarticle/99122 <![CDATA[Immune Modulation of Asian Folk Herbal Medicines and Related Chemical Components for Cancer Management]]>https://benthamscience.comarticle/84510 <![CDATA[Meet Our Editorial Board Member]]>https://benthamscience.comarticle/100109 <![CDATA[Gynaecological Cancer Diagnostics: 99mTc-Cisplatin Complex as a Future Approach for Early, Prompt and Efficient Diagnosis of Gynaecological Cancer]]>https://benthamscience.comarticle/92297Background: Gynaecological cancers (GCCa) are common and have a significant mortality rate all over the world. Early diagnosis of cancer can play a key role in the treatment and survival of a patient. Identification, staging, treatment, and monitoring of gynaecological malignancies is being done successfully by nuclear medicines.

Discussion: Currently, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) centered imaging techniques are being developed for use in patients with GCCa as a diagnostic tool. The present work elucidates several clinical studies on the use of radiopharmaceuticals, based on their effectiveness, in the early detection and management of GCCa. It also highlights the importance of reconsidering the biology for nuclear imaging as a future modality for early, rapid and efficient diagnosis of gynecological cancers. This comprehensive review is a part of our study designed to detect gynaecological cancers at an early stage using radionuclide complex, 99m Tc-Cisplatin.

Conclusion: This article summarizes the significance of radioscintigraphy such as single-photon emission computed tomography (SPECT) and PET for identification of GCCa in the experimental humans and animals.

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<![CDATA[Targeting p53-MDM2 Interaction Using Small Molecule Inhibitors and the Challenges Needed to be Addressed ]]>https://benthamscience.comarticle/97747 <![CDATA[Anti-tumor Drug Targets Analysis: Current Insight and Future Prospect ]]>https://benthamscience.comarticle/97752 <![CDATA[Meet Our Editorial Board Member ]]>https://benthamscience.comarticle/99567 <![CDATA[New Promises to Cure Cancer and Other Genetic Diseases/Disorders: Epi-drugs Through Epigenetics]]>https://benthamscience.comarticle/98700 <![CDATA[Identification of Genes Associated with Lung Adenocarcinoma Prognosis]]>https://benthamscience.comarticle/97791Objective: Lung cancer is the most prevalent cancer in the world, and lung adenocarcinoma is the most common lung cancer subtype. Identification and determination of relevant prognostic markers are the key steps to personalized cancer management.

Methods: We collected the gene expression profiles from 265 tumor tissues of stage I patients from The Cancer Genome Atlas (TCGA) databases. Using Cox regression model, we evaluated the association between gene expression and the overall survival time of patients adjusting for gender and age at initial pathologic diagnosis.

Results: Age at initial pathologic diagnosis was identified to be associated with the survival, while gender was not. We identified that 15 genes were significantly associated with overall survival time of patients (FDR < 0.1). The 15-mRNA signature- based risk score was helpful to distinguish patients of high-risk group from patients of low-risk group.

Conclusion: Our findings reveal novel genes associated with lung adenocarcinoma survival and extend our understanding of how gene expression contributes to lung adenocarcinoma survival. These results are helpful for the prediction of the prognosis and personalized cancer management.

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<![CDATA[Therapeutic Potential of Endophytic Compounds: A Special Reference to Drug Transporter Inhibitors]]>https://benthamscience.comarticle/98031