<![CDATA[Lymphoma]]> https://www.eurekaselect.com RSS Feed for Disease Wise Article | BenthamScience EurekaSelect (+http://eurekaselect.com) Fri, 29 Mar 2024 15:54:55 +0000 <![CDATA[Lymphoma]]> https://www.eurekaselect.com https://www.eurekaselect.com <![CDATA[Conspectus of Phytoconstituents and Pharmacological Activities of <i>Barleria lupulina</i> Lindl.: A Review]]>https://www.eurekaselect.comarticle/105191 <![CDATA[Exploring Molecular Approaches in Amyotrophic Lateral Sclerosis: Drug Targets from Clinical and Pre-Clinical Findings]]>https://www.eurekaselect.comarticle/106172 <![CDATA[Recent Advances in Herbal Nanomedicines for Cancer Treatment]]>https://www.eurekaselect.comarticle/106886 <![CDATA[Recent Advances in Chemotherapeutic Implications of Deguelin: A Plant- Derived Retinoid]]>https://www.eurekaselect.comarticle/103986 <![CDATA[Comprehensive Analysis Reveals GPRIN1 is a Potential Biomarker for Non-sm all Cell Lung Cancer]]>https://www.eurekaselect.comarticle/106983Background: Non-small cell lung cancer (NSCLC) is one of the most leading cause of tumor related mortality worldwide. However, the prognosis of NSCLC remained to be poor and the mechanisms remained to be further investigated.

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

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

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

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

]]>
<![CDATA[Advances in Sickle Cell Disease Treatments]]>https://www.eurekaselect.comarticle/107249 <![CDATA[New Perspectives in the Pharmacological Potential of Naringin in Medicine]]>https://www.eurekaselect.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.

]]>
<![CDATA[Targeting Protein Degradation in Cancer Treatment]]>https://www.eurekaselect.comarticle/107212 <![CDATA[Dual-target Inhibitors Based on BRD4: Novel Therapeutic Approaches for Cancer]]>https://www.eurekaselect.comarticle/107247Background: Currently, cancer continues being a dramatically increasing and serious threat to public health. Although many anti-tumor agents have been developed in recent years, the survival rate of patients is not satisfactory. The poor prognosis of cancer patients is closely related to the occurrence of drug resistance. Therefore, it is urgent to develop new strategies for cancer treatment. Multi-target therapies aim to have additive or synergistic effects and reduce the potential for the development of resistance by integrating different pharmacophores into a single drug molecule. Given the fact that majority of diseases are multifactorial in nature, multi-target therapies are being exploited with increasing intensity, which has brought improved outcomes in disease models and obtained several compounds that have entered clinical trials. Thus, it is potential to utilize this strategy for the treatment of BRD4 related cancers. This review focuses on the recent research advances of dual-target inhibitors based on BRD4 in the aspect of anti-tumor.

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

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

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

]]>
<![CDATA[Glycyrrhizic Acid Derivatives as New Antiviral and Immune Modulating Agents]]>https://www.eurekaselect.comarticle/104350 <![CDATA[Design, Synthesis and Biological Activity of New Hydroxamic Acids Containing 2-Imidazolylphenyl(oxy/thio)alkanoic Fragment]]>https://www.eurekaselect.comarticle/104497Background: Histone Deacetylase (HDAC) inhibitors are a new class of therapeutic compounds that show promising results in a series of preclinical and clinical anticancer studies. Hydroxamic acids belong to one of the most significant classes of HDAC inhibitors. The member vorinostat (SAHA) was approved by the U.S. Food and Drug Administration for the treatment of cutaneous T-cell lymphoma.

Methods: A series of eight novel hydroxamic acids containing 2-imidazolylphenyl(oxy/thio) alkanoic fragment designed to target Histone Deacetylase (HDAC) were synthesized in five steps from easily accessible 2(3H)-benzoxazolones and 2(3H)-benzthiazolones. The newly synthesized compounds were characterized by 1H, 13C NMR, and elemental analysis.

Results: The structure-activity relationship was examined via linker length alternation and variation of the heteroatom (oxygen or sulfur) and chlorine substitution pattern of the starting materials. The compounds were tested for their cytotoxic activity against two human cancer cell lines (HT-29 and MDA-MB-231). Our data indicate that the compound 6.1d is active in the micromolar range with IC50 of 9.7 μM for MDA-MB-231 cells. DNA fragmentation analysis of the most active compounds confirmed that apoptosis could be one of the mechanisms involved in cell death.

Conclusion: Taken together, the results revealed that 6d may become a promising lead compound for new anticancer drugs discovery.

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

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

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

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

]]>
<![CDATA[The Antitumor Effects of Icaritin Against Breast Cancer is Related to Estrogen Receptors]]>https://www.eurekaselect.comarticle/106989Objective: We aim to investigate the anticancer effects and mechanisms of icaritin against breast cancer.

Materials and Methods: Both estrogen receptor (ER) positive breast cancer cells MCF- 7 and ER-negative MDA-MB-231 cells were employed. We examined the effects of icaritin on the proliferation and migration by wound healing assay and transwell assay. Cell apoptosis and cell cycle of MCF-7 and MDA-MB-231 cells were analyzed using Flow cytometry. Cell autophagy of MCF-7 and MDA-MB-231 cells was assessed by western blotting, acridine orange staining and confocal microscopy. We also detected the expression of apoptosis-related genes by western blotting. In addition, an autophagy inhibitor was used to investigate whether cytoprotective autophagy was induced. Meanwhile, an ER inhibitor was utilized to explore whether ER was involved in autophagy.

Results: Icaritin inhibited the proliferation and migration, and induced cell cycle arrest of both MDA-MB-231 and MCF-7 cells. Icaritin significantly induced apoptosis of MDA-MB- 231 cells by activating caspase-3. And icaritin stimulated autophagy in MCF-7 cells, as evidenced by increased LC3II/LC3I, enhanced p62 degradation, the accumulation of endogenous LC3 puncta formation, and the increased autophagy flux. Icaritin induced autophagy through upregulating the phosphorylation of AMPK and ULK1. Chloroquine, an autophagy inhibitor, increased icaritin-induced apoptosis and proliferation inhibition of MCF-7 cells. Meanwhile, tamoxifen, an ER inhibitor, reversed icaritin-induced autophagy and proliferation inhibition of MCF-7 cells.

Conclusion: Our study demonstrated that the antitumor effects of icaritin against breast cancer are related to ER, which suggested that the status of ER should be considered in the clinical application of icaritin.

]]>
<![CDATA[Optimized Radial Basis Neural Network for Classification of Breast Cancer Images]]>https://www.eurekaselect.comarticle/106686 Introduction: Nowadays, cancer is considered the leading cause of death globally. Breast cancer is the most common cancer among females. It is possible to develop breast cancer while breast-feeding a baby, but it is rare. Mammography is one of the most effective methods used in hospitals and clinics for early detection of breast cancer. Various researchers are used in artificial intelligence- based mammogram techniques. This process of mammography will reduce the death rate of the patients affected by breast cancer. This process is improved by the image analysing, detection, screening, diagnosing, and other performance measures.

Methods: The radial basis neural network will be used for classification purposes. The radial basis neural network is designed with the help of the optimization algorithm. The optimization is to tune the classifier to reduce the error rate with the minimum time for the training process. The cuckoo search algorithm will be used for this purpose.

Results: Thus, the proposed optimum RBNN is determined to classify breast cancer images. In this, the three sets of properties were classified by performing the feature extraction and feature reduction. In this breast cancer MRI image, the normal, benign, and malignant is taken to perform the classification. The minimum fitness value is determined to evaluate the optimum value of possible locations. The radial basis function is evaluated with the cuckoo search algorithm to optimize the feature reduction process. The proposed methodology is compared with the traditional radial basis neural network using the evaluation parameter like accuracy, precision, recall and f1-score. The whole system model is done by using Matrix Laboratory (MATLAB) with the adaptation of 2018a since the proposed system is most efficient than most recent related literature.

Conclusion: Thus, it concluded with the efficient classification process of RBNN using a cuckoo search algorithm for breast cancer images. The mammogram images are taken into recent research because breast cancer is a major issue for women. This process is carried to classify the various features for three sets of properties. The optimized classifier improves performance and provides a better result. In this proposed research work, the input image is filtered using a wiener filter, and the classifier extracts the feature based on the breast image.]]> <![CDATA[New Spirocyclic Hydroxamic Acids as Effective Antiproliferative Agents]]>https://www.eurekaselect.comarticle/106937Aims: The main goal of this work is to synthesize new original spirocyclic hydroxamic acids, investigate their cytotoxicity against the panel of tumor cell lines and possible mechanism of action of these active compounds.

Background: Hydroxamic acids are one of the promising classes of chemical compounds with proven potential anticancer properties. This is manifested in the presence of metal chelating and antioxidant activities, the ability to inhibit histone deacetylase enzymes and a chemosensitizing effect against well known cytostatics.

Objective: Original spirocyclic hydroxamic acids were synthesized and spectra of their antiproliferative activities were investigated.

Methods: The cytotoxic activities on different tumor lines (SH-SY5Y, HeLa and healthy cells HEK-293) were investigated and determined possible underlying mechanisms of their activity.

Results: New original spirocyclic hydroxamic acids were synthesized. These compounds exhibit antiproliferative properties against various tumor cultures cells and also exhibit antioxidant activity, a depolarizing effect on the mitochondrial membrane, inhibit the activity of the histone deacetylase enzyme, and also decrease of basal glycolysis and glycolytic capacity reserve of HeLa and SH-SY5Y tumor cell lines.

Conclusion: The most promising are compounds 5j-l containing two chlorine atoms as substituents in the quinazoline part of the molecule and hydroxamate function. Therefore, these compounds can be considered as hit compounds for the development on their basis multi-target anticancer agents.

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

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

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

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

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

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

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

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

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

]]>
<![CDATA[Neuro-AIDS: Current Status and Challenges to Antiretroviral Drug Therapy (ART) for Its Treatment]]>https://www.eurekaselect.comarticle/107090Introduction: The infiltration of HIV into the brain alters the functions of the nervous system known as Neuro-AIDS. It leads to neuronal defects clinically manifested by motor and cognitive dysfunctions.

Materials and Methods: Current antiretroviral therapy can prevent viral replication but cannot cure the disease completely. HAART-Highly active antiretroviral therapy is used for the treatment of HIV infection. Challenges in neuro-AIDS therapy are as shown in the graphical abstract. One of the challenges is latent viral reservoirs like the brain; which act as a sanctuary site for viruses. Nearly ~50% of HIV patients show neuropathological signs. Nervous system related disorders, including AIDS dementia, sensory neuropathy, and myelopathy have a 25% of prevalence in patients having access to a highly active combination of antiretroviral therapy.

Results and Conclusions: Brain is one of the viral sanctuary sites for HIV. The current need of neuro-AIDS therapy is to target the brain as a viral reservoir. Drugs should cross or bypass the blood-brain barrier to reach the brain with effective concentrations. Current research on novel drug delivery approaches may prove helpful in treating neuro-AIDS and related disorders effectively.

]]>
<![CDATA[Data Tagging in Medical Images: A Survey of the State-of-Art]]>https://www.eurekaselect.comarticle/104625 <![CDATA[Targeted Protein Degradation: An Emerging Therapeutic Strategy in Cancer]]>https://www.eurekaselect.comarticle/105757 <![CDATA[Interleukin-19 as an Immunoregulatory Cytokine]]>https://www.eurekaselect.comarticle/106097 <![CDATA[MicroRNA-372-3p Predicts Response of TACE Patients Treated with Doxorubicin and Enhances Chemosensitivity in Hepatocellular Carcinoma]]>https://www.eurekaselect.comarticle/106664

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

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

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

Conclusion: Our study demonstrated that miR-372-3p acts as a tumor suppressor in HCC and can act as a predictor biomarker for drug response. Furthermore, the data referred for the first time its potential role in drug sensitivity that might be a therapeutic target for HCC.]]> <![CDATA[Targeting Small Molecule Tyrosine Kinases by Polyphenols: New Move Towards Anti-tumor Drug Discovery]]>https://www.eurekaselect.comarticle/100217Background: Cancer is a complex disease involving genetic and epigenetic alteration that allows cells to escape normal homeostasis. Kinases play a crucial role in signaling pathways that regulate cell functions. Deregulation of kinases leads to a variety of pathological changes, activating cancer cell proliferation and metastases. The molecular mechanism of cancer is complex and the dysregulation of tyrosine kinases like Anaplastic Lymphoma Kinase (ALK), Bcr-Abl (Fusion gene found in patient with Chronic Myelogenous Leukemia (CML), JAK (Janus Activated Kinase), Src Family Kinases (SFKs), ALK (Anaplastic lymphoma Kinase), c-MET (Mesenchymal- Epithelial Transition), EGFR (Epidermal Growth Factor receptor), PDGFR (Platelet-Derived Growth Factor Receptor), RET (Rearranged during Transfection) and VEGFR (Vascular Endothelial Growth Factor Receptor) plays major role in the process of carcinogenesis. Recently, kinase inhibitors have overcome many problems of traditional cancer chemotherapy as they effectively separate out normal, non-cancer cells as well as rapidly multiplying cancer cells.

Methods: Electronic databases were searched to explore the small molecule tyrosine kinases by polyphenols with the help of docking study (Glide-7.6 program interfaced with Maestro-v11.3 of Schrödinger 2017) to show the binding energies of polyphenols inhibitor with different tyrosine kinases in order to differentiate between the targets.

Results: From the literature survey, it was observed that the number of polyphenols derived from natural sources alters the expression and signaling cascade of tyrosine kinase in various tumor models. Therefore, the development of polyphenols as a tyrosine kinase inhibitor against targeted proteins is regarded as an upcoming trend for chemoprevention.

Conclusion: In this review, we have discussed the role of polyphenols as chemoreceptive which will help in future for the development and discovery of novel semisynthetic anticancer agents coupled with polyphenols.

]]>
<![CDATA[Statins as the Controlling Agents for Non-Hodgkin's Lymphomas via Increasing the Casein Kinase 2 Interacting Protein-1: A Hypothesis]]>https://www.eurekaselect.comarticle/99305Background: Non-Hodgkin's lymphomas (NHL), derived from B- or T-cell, consist of a heterogeneous group of malignant lymphoproliferative disorders. Knockdown of Casein kinase 2 interacting protein-1 (CKIP-1) in NHL promoted cell proliferation and inhibited apoptosis via enhancing phosphorylated Protein Kinase B (PKB or AKT) expression. Statins are the class of drugs that inhibit the ratelimiting step of the mevalonate pathway, which is essential for the biosynthesis of various compounds, including cholesterol. Also, statins have anticancer properties being mediated by different mechanisms.

Methods: A search on databases like Scopus and PubMed with keywords such as statin and non- Hodgkin's lymphomas was performed and Kyoto Encyclopedia of Genes and Genomes (KEGG) website was used to evaluate and reconfirm the involved cellular signaling pathway.

Results: CKIP-1 is involved in the regulation of cell proliferation and apoptosis while plays an important role in many cancers. We can hypothesize that statins may increase the expression levels of CKIP-1 which could contribute to the reductions in phospho-AKT level. Hence, they may ameliorate the NHL patients via suppressing AKT phosphorylation and increasing CKIP- expression.

Conclusion: Present review confirms the positive effect of statins on NHL by increasing CKIP-1 and reducing cell proliferation, subsequently.

]]>
<![CDATA[Design, Synthesis and Anticancer Activity of Site Specific Short Chain Cationic Peptide]]>https://www.eurekaselect.comarticle/97748Background: In spite of current progress in treatment methods, cancer is a major source of morbidity and death rate all over the world. Traditional chemotherapeutic agents aim to divide cancerous cells, are often associated with deleterious side effects to healthy cells and tissues. Host defense peptides Cecropin A and B obtained from insects are capable to lyses various types of human cancer cells at peptide concentrations which are not fatal to normal eukaryotic cells.

Methods: In the present work we have designed short chain α-helical linear and cyclic peptide from cecropin A having same cationic charge, hydrophobicity and helicity. Synthesis of designed novel short chain linear (10) and cyclic compound (12) was accomplished by using solution phase method. All the coupling reactions were carried out by using dicyclohexylcarbodiimide (DCC) as the coupling reagent at room temperature in the presence of N-methylmorpholine (NMM) as the base. The Structure of newly synthesized peptidse were elucidated by 1H-NMR, 13C-NMR, FT-IR, FABMS and elemental analysis data.Cytotoxicity of synthesized compound was tested against Dalton’s Lymphoma Ascites (DLA), Ehrlich’s Ascites Carcinoma (EAC) and MCF-7 cell lines by using MTT assay and 5-FU as reference compound.

Result: From biological assessment,it was found that short chain cyclicpeptide12 showed high level of cytotoxic activity against DLA and EAC cell lines.

Conclusion: By utilizing a structure-based rational approach to anticancer peptide design from cecropin A, we were able to develop short chain linear and cyclic peptides having same charge, hydrophobicity and with improved activity. Systematically removing amino acids, we were able to retaining peptide charge and hydrophobicity/hydrophilicity in linear and cyclic peptide which results to optimize the anticancer activity against DLA and EAC cell lines.

]]>
<![CDATA[S-Phase Kinase-Associated Protein-2 and Nuclear Factor-kappa Beta as Molecular Targets of Oral Burkitt’s Lymphoma Cell Induced by Quinolinone Derivate-Vesnarinone]]>https://www.eurekaselect.comarticle/92996Background: 3,4-Dihydro-6-[4-{3,4-dimethoxybenzoyl}-1-piperazinyl]-2(1H)-quinolinone (vesnarinone), a novel inotropic drug with unique and complex mechanisms of action, is known to show antitumor activity against several human malignancies. In the present study, vesnarinone-induced signal transduction of S-phase kinase-associated protein 2 (Skp2) and Nuclear Factor-kappa Beta (NF-κB) as molecular targets of oral malignant Burkitt’s lymphoma (Raji cells) was evaluated.

Materials and Methods: Raji cells were incubated with vesnarinone at concentrations of 0, 1.25x10-2, 2.50x10-2, or 5.0x10-2 Molar. After 24 h, chemotactic cell migration was examined by a Boyden chamber kit. Apoptosis induction was observed by caspase-9 colorimetric assay. To evaluate levels of Skp2, NF-kB, and α-tubulin, Western blot analysis was performed.

Results: Vesnarinone markedly suppressed chemotactic cell migration and significantly induced apoptosis by increasing the caspase-9 activity of Raji cells through down regulation of Skp2 and NF-κB.

Conclusion: Vesnarinone decreased the expression of Skp2 and NF-κB indicating these molecules may be targeted for the treatment of oral malignant Burkitt’s lymphoma (BL). The results of this work offer a promising therapeutic approach for BL tumors.

]]>
<![CDATA[Altered Expression of MicroRNAs in the Bone Marrow of Multiple Myeloma Patients and their Relationship to Cytogenetic Aberrations]]>https://www.eurekaselect.comarticle/105422Background: Multiple Myeloma (MM) is a complex hematologic malignancy, driven by several genetic and epigenetic alterations. MiRNAs as biomarkers have become a rapidly growing research area in the last decade.

Aim: The aim was to study the expression pattern of selected miRNAs and to explore the impact of cytogenetic aberrations in MM patients for therapeutic tools.

Patients and Methods: Forty Egyptian adult patients were selected for the study with symptomatic newly diagnosed MM disease. Bone marrow samples were collected to investigate twelve miRNAs selected according to their relation to the most common cytogenetic aberrations with relevant prognostic value. The relative expression of the selected miRNAs was determined using a real-time PCR technique. Fluorescence In Situ Hybridization (FISH) technique was performed for cytogenetic analysis.

Results: Eight miRNAs were down-regulated [miR-15a (p<0.001), miR214-3p (p<0.001), miR135b (p<0.001), miR19a-3p (p<0.001), miR19b-3p ((p=0.026), miR30e-5p (NS), miR133a (NS), miR146a- 5p (p<0.001)]. Four miRNAs were up-regulated [miR99b-5p (p=0.028), miR125a-3p (p=0.004), let7b- 5p (p<0.001), let7c-5p (p<0.001)]. Significant relation was observed between positive 14q32 rearrangement using the break apart re-arrangement probe for 14q32.33 locus and lower expression levels of miR15a (p= 0.014), 214-3p (p=0.046), 99b-5p (p=0.014), 146a-5p (p=0.041). A higher expression level of miR30e-5p was significantly related to positive 14q32 rearrangement.

Conclusion: Deregulated miRNAs were identified and the association with 14q32 rearrangement and MM pathogenesis has been determined.

]]>
<![CDATA[Co-existence of Follicular Lymphoma in the Lymph Node with High-grade B Cell Lymphoma in the Bone Marrow of a Patient with Spontaneous Tumor Lysis Syndrome]]>https://www.eurekaselect.comarticle/104086 <![CDATA[HIV-Related Lymphoproliferative Diseases in the Era of Combination Antiretroviral Therapy]]>https://www.eurekaselect.comarticle/105832 <![CDATA[The Potential of Flavonoids and Tannins from Medicinal Plants as Anticancer Agents]]>https://www.eurekaselect.comarticle/106666 <![CDATA[Immunoliposomes: Synthesis, Structure, and their Potential as Drug Delivery Carriers]]>https://www.eurekaselect.comarticle/104878 <![CDATA[Drug Delivery Approaches for Doxorubicin in the Management of Cancers]]>https://www.eurekaselect.comarticle/102992Aim: We aimed to review the drug delivery approaches including a novel drug delivery system of doxorubicin as an important anticancer drug.

Background: Doxorubicin (DOX) is widely used against breast, uterine, ovarian, lung and cervical cancer. It is listed among the essential medicines by WHO and is thus a very important drug that can be used to fight against cancer. Despite its effectiveness, the use of the drug is limited due to its dose-dependent toxicity. Several studies based on the DOX have suggested the need for novel drug delivery formulations in the treatment of malignant and cancerous diseases due to its cytotoxic nature.

Objective: This review focuses on the different formulations of DOX which is a useful drug in the management of cancers, but associated with toxicity thus these approaches found applicability in the reduction of its toxicity.

Methods: We searched the scientific database using cancer, DOX, and different formulations as the keywords. Here in only peer-reviewed research articles collected which were useful to our current work.

Results: This study is based on an examination of the recent advancements of its novel drug delivery formulations. DOX hydrochloride is the first liposomal anticancer drug, administered via the intravenous route, and also clinically approved for the treatment of lymphomas, leukemias, and solid tumors. DOX is prepared into a liposomal formulation that contains polyethylene glycol (PEG) layer around DOX containing liposome made by pegylation process. DOX also formulated in nano-formulations which is also discussed herein led to reduced toxicity and increased efficacy.

Conclusion: In the review, we described the significance of DOX in the form of different delivery approaches in the management of cancers with a reduction in the associated toxicity.

]]>
<![CDATA[An In Silico Immunogenicity Analysis for PbHRH: An Antiangiogenic Peptibody by Fusing HRH Peptide and Human IgG1 Fc Fragment]]>https://www.eurekaselect.comarticle/100029Background: Peptibodies, the hybrid of peptides and antibodies, represent a novel strategy in therapeutic use. Previously, we computationally designed an antiangiogenic peptibody PbHRH, which fused the HRH peptide with angiogenesis-suppressing effect and human IgG1 Fc fragment using Romiplostim as template. Molecular modeling and simulation results indicated that it would be a potential drug for the treatment of those angiogenesis related pathological disorders. However, its immunogenicity is not known.

Methods: Several bioinformatics tools are used to predict the potential epitopes for the evaluation of the immunogenicity of PbHRH. Romiplostim is set as the control. IEDB-recommended method is used in MHC-I and MHC-II binding prediction, and the IEDB web server (http://tools.iedb.org/immunogenicity/) is used to determine the MHC-I immunogenicity of each peptide.

Results: In this work, some peptides are predicted to have the potential ability to bind to MHC-I and MHC-II molecules both in PbHRH and Romiplostim as the potential epitopes. Most of these selected peptides are exactly the same. Allele frequency analysis shows a low population distribution. Combined with the analysis of MHC-I immunogenicity prediction, both HRH and PbHRH show low immunogenicity.

Conclusions: Some potential epitopes which could bind to both MHC-I and MHC-II molecules are predicted using bioinformatics tools. The comparative analysis with Romiplostim and the results of MHC-I immunogenicity prediction indicate the low immunogenicity of both HRH and PbHRH. Thus, we form a strategy to evaluate the immunogenicity of peptibodies for the future improvement.

]]>
<![CDATA[Role of BCL-2 Family Proteins in Apoptosis and its Regulation by Nutrients]]>https://www.eurekaselect.comarticle/103279 <![CDATA[A Phase I Study of OMN54 (Aneustat™) in Patients with Advanced Malignancies]]>https://www.eurekaselect.comarticle/107016Background/Objective: With the increasing interest in natural products, a phase I openlabel study of OMN54 (Aneustat™) in patients with advanced malignancies was initiated to determine toxicity, maximum tolerated dose (MTD), dose limiting toxicities (DLT), and pharmacokinetics (PK). OMN54 is a multitargeted agent, combining three Chinese botanicals; Ganoderma lucidium, Salvia miltiorrhiza and Scutellaria barbata.

Methods: Eligible patients (pts) were >18 years of age with advanced solid tumors, able to swallow oral capsules, ECOG performance status < 2, measurable disease as defined by RECIST 1.1 and adequate organ function.

Results: Twenty-two patients were enrolled in 6 dose levels, 2 with daily dosing and 4 with twicedaily dosing ranging from 1 to 5 grams daily. All were evaluated for toxicity and 20 for response. No treatment-related dose-limiting toxicities (DLTs) were reported and the recommended phase II dose (RP2D) was determined to be 2.5 g twice daily. Seven adverse events in 5 patients were reported as possibly drug-related; 6 were GI toxicity and 1 was a skin disorder. All were grade 1 except one grade 2 vomiting. No RECIST responses were seen. Six pts were treated with > 2 cycles; one for 8 cycles. Four patients had reductions in TGF –β and EGF, exploratory biomarkers possibly suggestive of a drug effect. Plasma half-lives of 1 -2 hours were noted for all parent drug chemical markers with no accumulation over time.

Conclusion: OMN54 was well tolerated, with no DLTs observed. Further studies at the RP2D will assess the biological activity.

]]>
<![CDATA[MiRNAs: A New Approach to Predict and Overcome Resistance to Anticancer Drugs]]>https://www.eurekaselect.comarticle/104080 <![CDATA[Elevated O-GlcNAcylation Promotes Malignant Phenotypes of Hypopharyngeal Squamous Cell Carcinoma by Stabilizing Nrf2 through Regulation of the PI3K/Akt Pathway]]>https://www.eurekaselect.comarticle/107357Background and Purpose: O-GlcNAcylation is a significant protein posttranslational modification with O-linked β-N-acetylglucosamine (GlcNAc) for intracellular signaling. Elevated O-GlcNAcylation contributes to cell proliferation, cell migration, cell apoptosis and signal transduction in various cancers. However, the expression level and functional role of O-GlcNAcylation in Hypopharyngeal Squamous Cell Carcinoma (HSCC) is not clearly elucidated. Nuclear factor erythroid-2-related factor 2 (Nrf2) is a master transcriptional factor that has been found to be aberrantly activated in HSCC. Here, we provide a molecular rationale between O-GlcNAcylation and Nrf2 in HSCC patients.

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

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

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

]]>
<![CDATA[Bortezomib – First Therapeutic Proteasome Inhibitor for Cancer Therapy: A Review of Patent Literature]]>https://www.eurekaselect.comarticle/105582Background: Bortezomib is a reversible inhibitor of proteasome proteins in mammalian cells. Bortezomib is proven to be cytotoxic to a number of tumor cells by disrupting their normal homeostatic mechanism and thereby, causing cell death. Currently, Bortezomib is prescribed for patients with multiple myeloma and mantle cell lymphoma.

Objective: This assessment highlights the overview of the recent patents of Bortezomib. This review includes patents grouped in sections like product patents, process patent, composition related patents as well as the treatment methodology. The objective of this article is to facilitate researchers with all existing patents at a single place.

Methods: Data were searched from various online databases. In which, paid databases include SciFinder® and Orbit®. Free databases include Patentscope® (WIPO), Worldwide Espacenet® (EPO), Google Patents and InPASS (Indian patent database).

Results: Several new processes and composition related patents of Bortezomib have been recently patented as its orange-book listed patents are going to soon expire during July 2022. Further, due to the problem of oxidation during development and long-term storage of Bortezomib formulation, a number of excipients are tried in these patents to stabilize the same. However, there is still a need for further development of an improved formulation of Bortezomib with better characteristics.

Conclusion: Extensive research has been carried out on various processes for preparing Bortezomib and the composition thereof. This type of dynamic research will clear the path for many generic players in the United States, which lead to the reduction of the price of the composition and thereby enhancing global health care at cheaper prices.

]]>
<![CDATA[Immunotherapy and Radiation Therapy in Renal Cell Carcinoma]]>https://www.eurekaselect.comarticle/105147Background: The management of renal cell carcinoma is rapidly evolving and immunotherapy, mostly consisting of immune checkpoint inhibitors, is revolutionizing the treatment scenario of metastatic patients. Novel fractionation schedules of radiotherapy, consisting of high doses in few fractions, can overcome the radioresistance of this tumor. Localized radiotherapy is associated with a systemic effect, known as the abscopal effect. This effect mediated by the immune system can be enhanced associating radiotherapy with immunotherapy.

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

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

]]>
<![CDATA[Bioactive Sterol Derivatives Isolated from the <i>Pleurotus djamor</i> var. Roseus Induced Apoptosis in Cancer Cell Lines]]>https://www.eurekaselect.comarticle/104977 Materials and Methods: Sequential fractionization and column chromatography methods were involved in compound isolation. The structures of the isolated compound were determined by NMR, GC/MS, and X-ray crystallography studies.

Results: The isolated compounds 1- 4 [D-mannitol (C1), ergosta-5,7,22-trien-3β-ol (C2), 5,8- epidioxy-ergosta-6-22-dien-3β-ol (C3), and palmitic acid (C4)] are white crystal and amorphous powder in nature. All these compounds were isolated from this mushroom for the first time. In vitro lipid peroxidation activities of isolated compounds were determined by ferric thiocyanate (FTC) and thiobarbituric acid (TBA) method. The sterol derivatives C2 and C3 compounds displayed strong antioxidant activity and were not significantly different (p<0.05) to α-tocopherol. This finding elaborates on the isolation of a cytotoxic compound C2 and C3 from P. djamor via a rapid elution method.

Conclusion: The compound C3 has exhibited better cytotoxic activity against MDA-MD-231 and EL4 cells. The present finding and data might provide new insights into the possible therapeutic and pharmaceutical use for the design of anti-cancer drugs from this edible mushroom.]]>
<![CDATA[Inulin as a Delivery Vehicle for Targeting Colon-Specific Cancer]]>https://www.eurekaselect.comarticle/106939 <![CDATA[Review on the Clinical Pharmacology of Hydroxychloroquine Sulfate for the Treatment of COVID-19]]>https://www.eurekaselect.comarticle/107245Background: As the number of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infected people is greatly increasing worldwide, the international medical situation becomes very serious. Potential therapeutic drugs, vaccine and stem cell replacement methods are emerging, so it is urgent to find specific therapeutic drugs and the best treatment regimens. After the publications on hydroxychloroquine (HCQ) with anti- SARS-COV-2 activity in vitro, a small, non-randomized, open-label clinical trial showed that HCQ treatment was significantly associated with reduced viral load in patients with coronavirus disease-19 (COVID-19). Meanwhile, a large prophylaxis study of HCQ sulfate for COVID-19 has been initiated in the United States. HCQ offered a promising efficacy in the treatment of COVID-19, but the optimal administration is still being explored.

Methods: We used the keyword "hydroxychloroquine" to conduct a literature search in PubMed to collect relevant literature on the mechanism of action of HCQ, its clinical efficacy and safety, pharmacokinetic characteristics, precautions for clinical use and drug interactions to extract and organize information.

Results: This paper reviews the mechanism, clinical efficacy and safety, pharmacokinetic characteristics, exposureresponse relationship and precautions and drug interactions of HCQ, and summarizes dosage recommendations for HCQ sulfate.

Conclusion: It has been proved that HCQ, which has an established safety profile, is effective against SARS-CoV-2 with sufficient pre-clinical rationale and evidence. Data from high-quality clinical trials are urgently needed worldwide.

]]>
<![CDATA[Genotype Driven Therapy for Non-Small Cell Lung Cancer: Resistance, Pan Inhibitors and Immunotherapy]]>https://www.eurekaselect.comarticle/96827 <![CDATA[Landmark Studies of Targeted Therapies for Advanced Non-Small Cell Lung Cancer: A Guide for Pulmonologists]]>https://www.eurekaselect.comarticle/105380 <![CDATA[The Apoptosis Mechanism of Epirubicin Combined with BCG on Human Bladder Cancer Cells]]>https://www.eurekaselect.comarticle/106277Aims: The purpose of our study was to explore the combination effect of epirubicin and Bacillus Calmette Guerin (BCG) and its mechanism.

Background: Bladder cancer is a threat to human health worldwide. Commonly used chemotherapy drugs and biotherapy have significant therapeutic effects on bladder cancer, but the mechanism and combined effects are still unclear.

Objective: To evaluate the anti-cancer effect of epirubicin combined with BCG on human bladder cancer cells, our studies were carried out.

Methods: The viability of human bladder cancer cells with epirubicin and/or BCG treatments was examined by Cell Counting Kit-8 (CCK-8) assay. Apoptosis and cell cycle phase were determined by flow cytometry analysis. Pre-apoptosis factors of caspase-3, p53, B-cell lymphoma 2 associated X protein (Bax) and anti-apoptosis factor of B-cell lymphoma 2 (Bcl-2) were detected by western blot.

Results: The viability of human bladder cancer with epirubicin or BCG treatment was decreased and the viability with epirubicin combined with BCG treatment was decreased more, which were determined by CCK-8 assay. Both epirubicin and BCG increased the apoptosis rate of human bladder cancer and arrested more cells into G0/G1 phase, which were tested by flow cytometry. The expression of caspase-3, p53 and Bax was increased and the expression of Bcl-2 was decreased with epirubicin treatment on human bladder cells, which were analyzed by western blot. The expression of caspase-3 and p53 was increased with BCG treatment, which was examined by western blot.

Conclusion: Epirubicin induced apoptosis in human bladder cancer cells by up-regulating the expression of proapoptotic factors (caspase-3, p53 and Bax) and down-regulating the expression of anti-apoptotic factor (Bcl-2). BCG promoted apoptosis of human bladder cancer cells by up-regulating the expression of caspase-3 and p53. BCG plays a potential role at the time of the combination of epirubicin and BCG on bladder cancer cells in early stage. Both epirubicin and BCG affected cell cycle distribution via arresting more bladder cancer cells at G0/G1 phase, which ultimately led bladder cancer proliferation in vitro and promoted apoptosis.

]]>
<![CDATA[The Early Results of Vertebral Pathological Compression Fracture of Extra- nodal Lymphoma with HIV-positive Patients Treated by Percutaneous Kyphoplasty]]>https://www.eurekaselect.comarticle/106487

Objective: The purpose of this study was to investigate the safety and efficacy of percutaneous kyphoplasty (PKP) in the treatment of vertebral pathological compression fracture of extra-nodal lymphoma in HIV-positive patients.

Methods: A retrospective analysis, from January 2016 to August 2019, was performed on 7 HIVpositive patients, 3 males and 4 females, with extra-nodal lymphoma with a vertebral pathological compression fracture. The patients were treated using percutaneous kyphoplasty in our hospital. Preoperative assessment of the patients was conducted regarding their hematological profile, biochemical indicators, liver and kidney function, blood coagulation function, CD4+T lymphocyte count and viral load. Subsequently, the patients were placed on highly active antiretroviral therapy (HAART) and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) regimen. Besides, antibiotics, nutritional support and immune-modulating drugs were also administered, rationally. Postoperatively, the height of the anterior edge of the injured vertebrae, Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) values were evaluated. Patients were also monitored for any complications related to the operation.

Results: The average CD4+T cell count for the patients was 164 (range 114 ~247 / ul), while the viral load was 26,269 (range 5,765 ~82,321 copies/ul). All patients received nutritional and immune support and registered significant improvements in the levels of ALB and Hb (P<0.05). In all cases, the operation was uneventful with neither cement leakage nor toxic reactions observed. Similarly, no opportunistic infections, other complications or deaths were reported. The height of the anterior vertebral body and the ODI score of the injured vertebrae were significantly improved immediately after surgery (P<0.05). Compared to the preoperative VAS (7.71±1.11), postoperative values were significantly reduced immediately after surgery (3.85±0.90) and at 2 weeks, 1 month and 6 months post-surgery: 2.71±0.76, 3.29±1.11, and 4.00±0.82, respectively (P<0.01).

Conclusion: Supported with appropriate perioperative treatment measures, PKP is safe and effective in the treatment of pathological vertebral compression fracture due to extra-nodal lymphoma in HIV-positive patients.]]>
<![CDATA[Exogenous Expression of WNT7A in Leukemia-Derived Cell Lines Induces Resistance to Chemotherapeutic Agents]]>https://www.eurekaselect.comarticle/106825Background: Dysregulations of the WNT pathway are implicated in the malignant transformation of different types of neoplasia. WNT7A is expressed in normal peripheral lymphocytes, but is decreased in the tumoral counterpart. Furthermore, the treatment of leukemic cells with recombinant WNT7A decreases proliferation, suggesting its possible use as a therapeutic biomolecule. This study aimed to evaluate the concomitant action of WNT7A and different chemotherapeutic agents over proliferation and cell death of leukemia/ lymphoma derived cell lines.

Methods: Ectopic expression of WNT7A was induced in CEM and BJAB cell lines by using a lentiviral system. RNA expression was analyzed by microarrays and qPCR, and protein expression was determined by Western Blot. Cell proliferation was measured by cell counting, metabolic activity by WST-1 assay, cell death and DNA content by flow cytometry.

Results: WNT7A ectopic expression was shown to decrease cell proliferation, but the apoptosis rate of leukemic cells was not altered. Moreover, these cells acquired resistance to doxorubicin, vincristine and MG-132. Cell cycle analysis reveals a decrease in G1 and an increase in S and G2 phases with a further upregulation of senescence- associated genes. Microarray analysis reveals that most gene expression changes were related to cancer and metabolic associated pathways. All those changes appear to be independent of the WNT canonical pathway regulation.

Conclusion: WNT7A negatively regulates cell proliferation in leukemic cell lines and promotes resistance to chemotherapeutic agents by inducing a senescence-like phenotype independently of the WNT canonical pathway.

]]>
<![CDATA[The Citrus Flavanone Hesperetin Induces Apoptosis in CTCL Cells <i>via</i> STAT3/Notch1/NFκB-Mediated Signaling Axis]]>https://www.eurekaselect.comarticle/105437

Objectives: Investigating the potential anticancer activities of Hesperetin in malignant hematolymphoid cell lines HuT78 and MJ, derived from patients with Cutaneous T-Cell Lymphomas (CTCL).

Methods: The cytotoxic effect of Hesperetin on two different CTCL cell lines, HuT78 and MJ, was assessed by MTS-based colorimetric assay. Apoptosis, cell cycle, ROS (Reactive Oxygen Species) and molecular analysis were performed using flow-cytometry and immunoblotting.

Results: Hesperetin-treated CTCL cells were arrested at the sub-G1 phase of cell cycle with the concomitant decrease in the expression of the cell cycle regulator protein cyclin B. In addition, the study found that the cellular treatment with Hesperetin caused an induction of apoptosis, which was independent of ROS generation. Hesperetin caused a significant decrease in the expression level of anti-apoptotic protein Bcl-xL and an increase in cleaved caspase-3 and PARP proteins in CTCL cells. Furthermore, Hesperetin treatment in CTCL cells down-regulated the expression of Notch1 and phosphorylation of STAT3 (Tyr705) and inhibited NFκBp65.

Conclusion: This study highlights the anticancer properties of Hesperetin. Which induces apoptosis in CTCL cells via STAT3/Notch1/NFκB mediated signaling pathway, suggesting that further development of this novel class of flavonoid may contribute to new drug discovery for certain hematolymphoid malignancies.]]>
<![CDATA[Hepatitis C Virus Infection and Treatment as Independent Prognostic Factors in Diffuse Large B-Cell Lymphoma Egyptian Patients]]>https://www.eurekaselect.comarticle/106519Background: Egypt is one of the highest hepatitis C virus (HCV) endemic areas. Chronic HCV infection has extra-hepatic manifestations, including non-Hodgkin lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) is commonly associated with HCV infection. The prognostic value of HCV infection and HCV treatment in patients with DLBCL remains unclear until now.

Objective: The aim of our study is to evaluate the impact of HCV infection and HCV treatment as independent prognostic factors on the event-free survival (EFS) and overall survival (OS) in Egyptian patients with HCV associated DLBCL.

Methods: This study included 353 patients with DLBCL, collected retrospectively. While 34 patients with HCV who received HCV antiviral therapy were collected prospectively. Patient’s characteristics were collected from the patient records at the time of diagnosis. The status of the patients about HCV infection and HCV treatment were also recorded. Disease progression, relapse, retreatment or deaths were also verified through medical records. EFS and OS were calculated.

Results: EFS and OS significantly decrease in HCV infected and HCV non-treated patients when compared with HCV non-infected and HCV treated patients, respectively. HCV infection but not HCV treatment was independently associated with EFS and OS using univariate and multivariate analysis.

Conclusion: Hepatitis C virus infection is an independent prognostic factor for EFS and OS in diffuse large B-cell lymphoma. HCV treatment is associated with higher EFS and OS but can not be considered as an independent prognostic factor.

]]>
<![CDATA[Chemical Profile and Anticancer Activity of Polyscias guilfoylei Leaf Essential Oil]]>https://www.eurekaselect.comarticle/99171Background: Polyscias guilfoylei, commonly called ‘geranium aralia’, is an erect shrub with dark green leaves. P. guilfoylei has been introduced to tropical countries and is generally cultivated in gardens for ornamental purposes. There are no previous studies on the essential oil of P. guilfoylei and its biological activities.

Objectives: In this study, we report the chemical profile of P. guilfoylei leaf essential oil and its anticancer activity tested by various in vitro and in vivo assays.

Methods: The chemical profile of P. guilfoylei leaf oil was elucidated by Gas Chromatographic analyses (GC-FID, GC-MS). Anticancer activity of P. guilfoylei leaf oil was tested by MTT, morphological observations, DNA ladder, comet, caspase, flow cytometry and in vivo assays.

Results: Gas chromatographic profiling of P. guilfoylei leaf oil identified 50 constituents (β-selinene 49.59%, α-selinene 21.68%, (Z)-falcarinol 11.65%). In MTT assay, P. guilfoylei leaf oil at 50, 25, 10, 5 and 1 μg/ml showed 98.6 ± 1.2, 95.3 ± 0.78, 76.8 ± 1.59, 43.6 ± 0.99 and 39.8 ± 1.17% DLA cell death, respectively (CD50 5.96 μg/ml). In flow cytometry, the majority of P. guilfoylei leaf oil (25 μg/ml) treated DLA cells showed an accumulation/cell arrest in G2M phase (61.7 ± 2.6%). In P. guilfoylei leaf oil treated mice (40 days), 5 animals (83.3%, each) were protected in 25, 50 mg/kg groups.

Conclusion: P. guilfoylei leaf oil, with minimal toxicity to normal cells, exhibited significant anticancer activity against lymphoma cells enhancing its potential as an anticancer agent.

]]>
<![CDATA[Copanlisib: Novel PI3K Inhibitor for the Treatment of Lymphoma]]>https://www.eurekaselect.comarticle/105302 <![CDATA[Roles of Medicinal Plants and Constituents in Gynecological Cancer Therapy: Current Literature and Future Directions]]>https://www.eurekaselect.comarticle/105854Gynecologic cancers, including cervical, primary peritoneal, ovarian, uterine/endometrial, vaginal and vulvar cancers and gestational trophoblastic disease, are characterized by abnormal cell proliferation in female reproductive cells. Due to the variable pathology of these cancers and the lack of appropriate screening tests in developing countries, cancer diagnosis can be reported in advanced stages in most women and this situation adversely affects prognosis and clinical outcomes of illness. For this reason, many researchers in the field of gynecological oncology have carried out many studies.

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

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

]]>
<![CDATA[Structure-based Drug Design Strategies in the Development of Small Molecule Inhibitors Targeting Bcl-2 Family Proteins]]>https://www.eurekaselect.comarticle/104480 <![CDATA[A Case Series of Malign Hyperechoic Breast Lesions]]>https://www.eurekaselect.comarticle/100506Background: Hyperechoic breast lesions are a rare group of breast masses in routine practice. Most of these lesions are benign. However, they rarely may be malignant. Hyperechoic lesions can be evaluated using the same criteria for malignant lesions. Clinical history, mammographic appearance, and certain sonographic features (non-circumscribed margins, irregular shape, presence of hypoechoic areas, nonparallel orientation, and association with microcalcifications can be suggestive of malignancy). In this article, hyperechoic breast lesions with malignant pathology have been presented.

Methods: Seven cases during breast ultrasound examination were detected.

Results: Four patients had invasive ductal carcinoma, 1 patient had invasive lobular carcinoma, 1 patient had high-grade ductal carcinoma in situ (DCIS), and 1 patient had lymphoma. Ultrasonography of the breast showed a heterogeneous appearance in all the patients, microcalcification in two patients, and an ambiguous contour in one patient.

Conclusion: Hyperechoic breast lesions should be evaluated using specific sonographic criteria to prevent misdiagnosis and identify patients who require biopsy and further examination.

]]>
<![CDATA[Artemia species: An Important Tool to Screen General Toxicity Samples]]>https://www.eurekaselect.comarticle/105658 <![CDATA[Synthesis, Antitumor Activity and Molecular Docking Studies on Seven Novel Thiazacridine Derivatives]]>https://www.eurekaselect.comarticle/105368Aim and Objective: In the last decades, cancer has become a major problem in public health all around the globe. Chimeric chemical structures have been established as an important trend on medicinal chemistry in the last years. Thiazacridines are hybrid molecules composed of a thiazolidine and acridine nucleus, both pharmacophores that act on important biological targets for cancer. By the fact it is a serious disease, seven new 3-acridin-9-ylmethyl-thiazolidine-2,4-dione derivatives were synthesized, characterized, analyzed by computer simulation and tested in tumor cells. In order to find out if the compounds have therapeutic potential.

Materials and Methods: Seven new 3-acridin-9-ylmethyl-thiazolidine-2,4-dione derivatives were synthesized through Michael addition and Knoevenagel condensation strategies. Characterization was performed by NMR and Infrared spectroscopy techniques. Regarding biological activity, thiazacridines were tested against solid and hematopoietic tumoral cell lines, namely Jurkat (acute T-cell leukemia); HL-60 (acute promyelocytic leukemia); DU 145 (prostate cancer); MOLT-4 (acute lymphoblastic leukemia); RAJI (Burkitt's lymphoma); K562 (chronic myelogenous leukemia) and normal cells PBMC (healthy volunteers). Molecular docking analysis was also performed in order to assess major targets of these new compounds. Cell cycle and clonogenic assay were also performed.

Results: Compound LPSF/AA-62 (9f) exhibited the most potent anticancer activity against HL-60 (IC50 3,7±1,7 μM), MOLT-4 (IC50 5,7±1,1 μM), Jurkat (IC50 18,6 μM), Du-145 (IC50 20±5 μM) and Raji (IC50 52,3±9,2 μM). While the compound LPSF/AA-57 (9b) exhibited anticancer activity against the K562 cell line (IC50 51,8±7,8 μM). Derivative LPSF/AA-62 (9f) did not interfere in the cell cycle phases of the Molt-4 lineage. However, the LPSF/AA-62 (9f) derivative significantly reduced the formation of prostate cancer cell clones. The compound LPSF/AA-62 (9f) has shown strong anchorage stability with enzymes topoisomerases 1 and 2, in particular due the presence of chlorine favored hydrogen bonds with topoisomerase 1.

Conclusion: The 3-(acridin-9-ylmethyl)-5-((10-chloroanthracen-9-yl)methylene)thiazolidine-2,4-dione (LPSF/AA-62) presented the most promising results, showing anti-tumor activity in 5 of the 6 cell types tested, especially inhibiting the formation of colonies of prostate tumor cells (DU-145).

]]>
<![CDATA[B7-H3-targeted Radioimmunotherapy of Human Cancer]]>https://www.eurekaselect.comarticle/96941Background: Targeted Radioimmunotherapy (RIT) is an attractive approach to selectively localize therapeutic radionuclides to malignant cells within primary and metastatic tumors while sparing normal tissues from the effects of radiation. Many human malignancies express B7-H3 on the tumor cell surface, while expression on the majority of normal tissues is limited, presenting B7-H3 as a candidate target for RIT. This review provides an overview of the general principles of targeted RIT and discusses publications that have used radiolabeled B7-H3-targeted antibodies for RIT of cancer in preclinical or clinical studies.

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

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

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

]]>
<![CDATA[Modulation of Immuno-biome during Radio-sensitization of Tumors by Glycolytic Inhibitors]]>https://www.eurekaselect.comarticle/90858 <![CDATA[Practical Approach to Children Presenting with Eosinophila and Hypereosinophilia]]>https://www.eurekaselect.comarticle/102379 500 cells/μL. It is classified into mild (500-1500 cells/μl), moderate (1500-5000 cells/μl) and severe for an eosinophil count > 5000 cells /μl. The term "hypereosinophilia” defines a condition characterized by a blood eosinophil count >1500 cells/μl in at least two consecutive tests made with a minimum of a 4-week interval. The causes of eosinophilia are various, and can be summarized by the acronym “APLV” which refers to Allergic disorders, Parasitic infections, Leukemia/ Lymphomas (and solid tumors) and Vasculitis-Immunodeficiency diseases, with allergic disorders and parasitic infections representing the most commonly identified causes. Allergic disorders are usually associated with mild eosinophilia, whereas values >20.000 cell/μl are highly suggestive for myeloproliferative disorders. Eosinophils may also be directly responsible for organ damage, mainly at cardiac, pulmonary and cutaneous level, deriving from the release of the granule products, of lipidic mediators and cytokines. Therefore, in the physician’s approach to a patient with persistent hypereosinophilia, it is also important to investigate the presence of organ involvement. In this review, we propose a diagnostic algorithm for children presenting with either blood eosinophilia or hypereosinophilia. This algorithm focuses on the patient’s history and clinical manifestations as the first step and the level and persistence of blood eosinophilia as the second, and this can help the physician to identify patients presenting with an elevated blood eosinophil count that need further laboratory or instrumental investigations.]]> <![CDATA[Design, Synthesis, and Anticancer Potential of the Enzyme (PARP-1) Inhibitor with Computational Studies of New Triazole, Thiazolidinone, - Thieno [2, 3-d] Pyrimidinones]]>https://www.eurekaselect.comarticle/103735Background: Thienopyrimidine, triazole and thiazolidinone derivatives have recently gained attention due to their effective pharmacological activities. They show antioxidant, antitumor, antimicrobial, antiviral, anti-inflammatory and analgesic properties.

Objective: Synthesis of new ethyl 2-amino-4-isopropyl-5-methylthiophene-3-carboxylate (2) was used as a starting material to produce 2-mercapto-methylthienopyrimidinone (3), (4) and 2- hydrazinyl-methylthienopyrimidinone (5), through high yields and evaluating anticancer activities.

Methods: A series of novel Schiff's bases (6-9) were produced after treatment of (5) with aldehydes. Triazolopyrimidinones (6a, 7a, 8a, 9a) were produced from cyclization of benzylidene (6-9) using Br2 / AcOH or dry pyridine /Ac2O. Thiazolidinones (6b, 7b, 8b, 9b) were synthesized from benzylidene (6-9) with mercaptoacetic acid.

Results: All the compounds were synthesized in good yields (55-85%) in a regularly actual system under mild condition. The new compounds have been established by means of diverse spectroscopic ways as IR, NMR and MS. The newly synthesized compounds were evaluated for their antiproliferative activity against the breast MCF-7 carcinoma cell line. Compound (7) showed promising anticancer activity with IC50 of 6.9 μM, and 40.8% of antioxidant effect as DPPH inhibition. Molecular docking of (7) showed ΔG values of-20.54 kcal/ mol and -25.60 kcal/ mol. Molecular dynamics simulation of (7) in complex with PARP-1 revealed RMSD of 3.00 Ǻ.

Conclusion: The QSAR study confirmed the presence of a relationship between anticancer activity and subdivided surface area descriptors with coefficient r2 = 0.98 with high predictive power.

]]>
<![CDATA[Ustekinumab-induced Sarcoidosis in a Patient with Psoriatic Arthritis]]>https://www.eurekaselect.comarticle/105250Background: Psoriatic Arthritis (PsA) is a chronic inflammatory disease that may affect different joints. Sarcoidosis is a Th-1 cell-related chronic granulomatous disease characterized by non-caseating granuloma formation. The coexistence of both the diseases is a rare entity. Ustekinumab, an IL12 / 23 inhibitor, has shown efficacy and safety in the treatment of PsA.

Objective: This study presents a case with ustekinumab-induced sarcoidosis in a patient with PsA.

Case Report: A 52 years old female patient with complaints of pain and swelling of the wrists, MCP, PIP and DIP joints and skin lesions was referred to our Rheumatology clinic. On her medical history, she had been under follow up for 5 years with the diagnosis of psoriasis and one year ago, she started to receive ustekinumab prescribed by a dermatologist. On physical examination, she had psoriasis skin lesions and arthritis of both wrists, MCP, PIP, DIP joints. Bilateral hilar lymphadenopathies were detected in the chest X-ray and thorax computed tomography. In laboratory tests, acute phase reactants and serum angiotensin-converting enzyme levels were high. Endobronchial ultrasonography biopsy was performed and non-caseating granuloma consistent with sarcoidosis was reported. Ustekinumab was discontinued, methotrexate and low-dose corticosteroid were started. The patient was clinically stable in the 6th month of the treatment and the findings were regressed.

Conclusion: Sarcoidosis development appears to be a new paradoxical effect of ustekinumab therapy, being another biological agent.

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

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

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

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

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

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

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

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

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

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

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

]]>
<![CDATA[Coexistence of Hodgkin and Non-Hodgkin Lymphoma; Composite Lymphoma [CL] in a Patient Presenting with Waxing and Waning Lymphadenopathy]]>https://www.eurekaselect.comarticle/101405Background: The coexistence of two or more types of lymphoma within the same organ at the same time of diagnosis is defined as composite lymphoma, a rare disease that has recently been identified in the literature. Pointedly, the concurrence may be Hodgkin lymphoma with a Non-Hodgkin lymphoma [NHL], either B or T cells, or two different entities of NHLs. Furthermore, this condition has been described concurrently or sequentially. In order for the diagnosis to be established, two or more distinct clones should be proven by morphological and laboratory tests.

Case Presentation: Herein, we cite a seventy-three-year old female patient with low-grade fever, waxing and waning cervical lymphadenopathy, whose biopsy of an axillary lymph node demonstrated the rare coexistence of Hodgkin and NHL, known as composite lymphoma.

Conclusion: Composite lymphomas pose a particular diagnostic challenge, and currently, there are no agreed standards for treatment.

]]>
<![CDATA[Utilization of Lipid-based Nanoparticles to Improve the Therapeutic Benefits of Bortezomib]]>https://www.eurekaselect.comarticle/103933 <![CDATA[Benzisothiazolone Derivatives Exhibit Cytotoxicity in Hodgkin’s Lymphoma Cells through NF-κB Inhibition and are Synergistic with Doxorubicin and Etoposide]]>https://www.eurekaselect.comarticle/104467Background: The authors investigated the NF-κB inhibitory role of three Benzisothiazolone (BIT) derivatives (1, 2 and 3) in Hodgkin’s Lymphoma cells (L428) which constitutively express activated NF-κB. All three compounds showed dose-dependent NF-κB inhibition (78.3, 70.7 and 34.6%) in the luciferase reporter gene assay and were found cytotoxic at IC50 values of 3.3μg/ml, 4.35μg/ml and 13.8μg/ml, respectively by the XTT assay. BIT 1and BIT 2 (but not BIT 3) suppressed both NF-κB subunits p50 and p65 in cytoplasmic and nuclear extracts in a concentration-dependent manner. Furthermore, BIT 1 showed a moderate synergistic effect with the standard chemotherapy drugs etoposide and doxorubicin, whereas BIT 2 and 3 showed a moderate additive effect to antagonistic effect. Cisplatin exhibited an antagonist effect on all the compounds tested under various concentrations, except in the case of 1.56μg/ml of BIT 3 with 0.156μg/ml of cisplatin. The compounds also inhibited the migration of adherent human lung adenocarcinoma cells (A549) in vitro. We conclude that especially BIT 1 and BIT 2 have in vitro anti-inflammatory and anti-cancer activities, which can be further investigated for future potential therapeutic use.

Methods: Inspired by the electrophilic sulfur in Nuphar alkaloids, monomeric and dimeric benzisothiazolones were synthesized from dithiodibenzoic acid and their NF-κB inhibitory role was explored. NF-κB inhibition and cytotoxicity of the synthesized derivatives were studied using luciferase reporter gene assay and XTTassay. Immunocytochemistry studies were performed using L428 cells. Cell migration assay was conducted using the A549 cell line. L428 cells were used to conduct combination studies and the results were plotted using CompuSyn software.

Results: Benzisothiazolone derivatives exhibited cytotoxicity in Hodgkin’s Lymphoma cells through NF-κB inhibition. Potent compounds showed suppression of both NF-κB subunits p50 and p65 in a concentrationdependent manner, both in cytoplasmic and nuclear extracts. Combination studies suggest that benzisothiazolone derivatives possess a synergistic effect with etoposide and doxorubicin. Furthermore, the compounds also inhibited the migration of A549 cells.

Conclusion: Benzisothiazolones bearing one or two electrophilic sulfur atoms as part of the heterocyclic framework exhibited cytotoxicity in Hodgkin’s Lymphoma cells through NF-κB inhibition. In addition, these derivatives also exhibited a synergistic effect with etoposide and doxorubicin along with the ability to inhibit the migration of A549 cells. Our study suggests that BIT-based new chemical entities could lead to potential anticancer agents.

]]>
<![CDATA[Regulatory T Cell Counts and Development of Malignancy in Patients with HIV Infection]]>https://www.eurekaselect.comarticle/105584Background: T-regulatory cells (Tregs) play an important role in maintaining homeostasis by attenuating the cytokine response to T-cell receptor (TCR) stimulation and by suppressing the functioning of neighboring immune cells. In Human Immunodeficiency Virus (HIV) infection, Tregs can be either beneficial, by suppressing generalized T-cell activation, or detrimental, by suppressing protective anti-HIV cell-mediated immunity. An imbalance of Tregs and effector T-cells can blunt immune responses to malignant cells or facilitate inflammation-mediated pathologies.

Objective: The purpose of our study was to explore the possible correlation between Tregs’ concentration and HIV infection’s parameters as well as the development of hematological and solid malignancies.

Methods: In a longitudinal prospective study, ex vivo phenotyping of fresh peripheral blood mononuclear cells from patients with primary HIV infection was performed at baseline. All patients were then followed up every 3 months and the development of solid or hematological malignancies was noted.

Results: A total of 155 patients were included in the study and the median follow-up period was 64 months. Treg counts were significantly higher among males, patients with high viral load (>350 copies/ml) and patients with virological failure to antiretroviral treatment (ART). Linear regression analysis showed a significant negative correlation between Treg levels and CD4 (+) T-cell counts. Patients with neoplasia had lower levels of Tregs while increasing levels showed a negative correlation with the development of neoplasia.

Conclusion: In our population of HIV-infected patients, high levels of Tregs were associated with disease progression, and low baseline levels were associated with a higher probability of developing neoplasia.

]]>
<![CDATA[Herbal Medicine for Slowing Aging and Aging-associated Conditions: Efficacy, Mechanisms and Safety]]>https://www.eurekaselect.comarticle/99616 <![CDATA[<i>Rhizoma Coptidis</i> for Alzheimer’s Disease and Vascular Dementia: A Literature Review]]>https://www.eurekaselect.comarticle/99540Background: Alzheimer’s disease (AD) and vascular dementia (VaD) are major types of dementia, both of which cause heavy economic burdens for families and society. However, no currently available medicines can control dementia progression. Rhizoma coptidis, a Chinese herbal medicine, has been used for >2000 years and is now gaining attention as a potential treatment for AD and VaD.

Methods: We reviewed the mechanisms of the active ingredients of Rhizoma coptidis and Rhizoma coptidis-containing Chinese herbal compounds in the treatment of AD and VaD. We focused on studies on ameliorating the risk factors and the pathological changes of these diseases.

Results: The Rhizoma coptidis active ingredients include berberine, palmatine, coptisine, epiberberine, jatrorrhizine and protopine. The most widely studied ingredient is berberine, which has extensive therapeutic effects on the risk factors and pathogenesis of dementia. It can control blood glucose and lipid levels, regulate blood pressure, ameliorate atherosclerosis, inhibit cholinesterase activity, Aβ generation, and tau hyperphosphorylation, decrease neuroinflammation and oxidative stress and alleviate cognitive impairment. Other ingredients (such as jatrorrhizine, coptisine, epiberberine and palmatine) also regulate blood lipids and blood pressure; however, there are relatively few studies on them. Rhizoma coptidis-containing Chinese herbal compounds like Huanglian-Jie-Du-Tang, Huanglian Wendan Decoction, Banxia Xiexin Decoction and Huannao Yicong Formula have anti-inflammatory and antioxidant stress activities, regulate insulin signaling, inhibit γ-secretase activity, neuronal apoptosis, tau hyperphosphorylation, and Aβ deposition, and promote neural stem cell differentiation, thereby improving cognitive function.

Conclusion: The “One-Molecule, One-Target” paradigm has suffered heavy setbacks, but a “multitarget- directed ligands” strategy may be viable. Rhizoma coptidis active ingredients and Rhizoma coptidiscontaining Chinese herbal compounds have multi-aspect therapeutic effects on AD and VaD.

]]>
<![CDATA[Manipulation of the Immune System for Cancer Defeat: A Focus on the T Cell Inhibitory Checkpoint Molecules]]>https://www.eurekaselect.comarticle/94306 <![CDATA[Recent Progress in Histone Deacetylase Inhibitors as Anticancer Agents]]>https://www.eurekaselect.comarticle/93733 <![CDATA[Preclinical and Clinical Studies on Bryostatins, A Class of Marine-Derived Protein Kinase C Modulators: A Mini-Review]]>https://www.eurekaselect.comarticle/105477 <![CDATA[Isoform-Selective PI3K Inhibitors for Various Diseases]]>https://www.eurekaselect.comarticle/103500 <![CDATA[Knockdown of Enhancer of Zeste Homolog 2 Affects mRNA Expression of Genes Involved in the Induction of Resistance to Apoptosis in MOLT-4 Cells]]>https://www.eurekaselect.comarticle/104079Background: The Enhancer of Zeste Homolog 2 (EZH2) is a subunit of the polycomb repressive complex 2 that silences the gene transcription via H3K27me3. Previous studies have shown that EZH2 has an important role in the induction of the resistance against the Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL)-Induced Apoptosis (TIA) in some leukemia cells.

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

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

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

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

]]>
<![CDATA[Analysis of Four Types of Leukemia Using Gene Ontology Term and Kyoto Encyclopedia of Genes and Genomes Pathway Enrichment Scores]]>https://www.eurekaselect.comarticle/95504Aim and Objective: Leukemia is the second common blood cancer after lymphoma, and its incidence rate has an increasing trend in recent years. Leukemia can be classified into four types: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and chronic myelogenous leukemia (CML). More than forty drugs are applicable to different types of leukemia based on the discrepant pathogenesis. Therefore, the identification of specific drug-targeted biological processes and pathways is helpful to determinate the underlying pathogenesis among such four types of leukemia.

Methods: In this study, the gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that were highly related to drugs for leukemia were investigated for the first time. The enrichment scores for associated GO terms and KEGG pathways were calculated to evaluate the drugs and leukemia. The feature selection method, minimum redundancy maximum relevance (mRMR), was used to analyze and identify important GO terms and KEGG pathways.

Results: Twenty Go terms and two KEGG pathways with high scores have all been confirmed to effectively distinguish four types of leukemia.

Conclusion: This analysis may provide a useful tool for the discrepant pathogenesis and drug design of different types of leukemia.

]]>
<![CDATA[Akt Pathway Inhibitors]]>https://www.eurekaselect.comarticle/104753 <![CDATA[DLEU1: A Functional Long Noncoding RNA in Tumorigenesis]]>https://www.eurekaselect.comarticle/103829

Methods: In this review, current studies concerning the biological functions and mechanisms of DLEU1 in tumor development are summarized and analyzed; the related researches are collected through a systematic retrieval of PubMed.

Results: DLEU1 is a novel cancer-associated lncRNA that has been proved to be abnormally elevated in various malignancies, containing osteosarcoma, glioma, glioblastoma multiforme, hepatocellular carcinoma, bladder cancer, cervical cancer, non-small cell lung cancer, pancreatic ductal adenocarcinoma, colorectal cancer, oral squamous cell carcinoma, endometrial cancer, gastric cancer, Burkitt lymphoma and ovarian carcinoma. Besides, lncRNA LDEU1 has been demonstrated involving in the procession of proliferation, migration, invasion and inhibition of apoptosis of cancer cells.

Conclusion: Long non-coding RNA DLEU1 is likely to represent an available biomarker or a potential therapeutic target in multiple tumors.]]>
<![CDATA[Anticancer Activity of Platinum (II) Complex with 2-Benzoylpyridine by Induction of DNA Damage, S-Phase Arrest, and Apoptosis]]>https://www.eurekaselect.comarticle/102264Objective: To overcome the disadvantages of cisplatin, numerous platinum (Pt) complexes have been prepared. However, the anticancer activity and mechanism of Pt(II) complexed with 2-benzoylpyridine [Pt(II)- Bpy]: [PtCl2(DMSO)L] (DMSO = dimethyl sulfoxide, L = 2-benzoylpyridine) in cancer cells remain unknown.

Methods: Pt(II)-Bpy was synthesized and characterized by spectrum analysis. Its anticancer activity and underlying mechanisms were demonstrated at the cellular, molecular, and in vivo levels.

Results: Pt(II)-Bpy inhibited tumor cell growth, especially HepG2 human liver cancer cells, with a halfmaximal inhibitory concentration of 9.8±0.5μM, but with low toxicity in HL-7702 normal liver cells. Pt(II)- Bpy induced DNA damage, which was demonstrated through a marked increase in the expression of cleavedpoly (ADP ribose) polymerase (PARP) and gamma-H2A histone family member X and a decrease in PARP expression. The interaction of Pt(II)-Bpy with DNA at the molecular level was most likely through an intercalation mechanism, which might be evidence of DNA damage. Pt(II)-Bpy initiated cell cycle arrest at the S phase in HepG2 cells. It also caused severe loss of the mitochondrial membrane potential; a decrease in the expression of caspase-9 and caspase-3; an increase in reactive oxygen species levels; the release of cytochrome c and apoptotic protease activation factor; and the activation of caspase-9 and caspase-3 in HepG2 cells, which in turn resulted in apoptosis. Meanwhile, changes in p53 and related proteins were observed including the upregulation of p53, the phosphorylation of p53, p21, B-cell lymphoma-2-associated X protein, and NOXA; and the downregulation of B-cell lymphoma 2. Moreover, Pt(II)-Bpy displayed marked inhibitory effects on tumor growth in the HepG2 nude mouse model.

Conclusion: Pt(II)-Bpy is a potential candidate for cancer chemotherapy.

]]>
<![CDATA[Anticancer Effect of Amygdalin (Vitamin B-17) on Hepatocellular Carcinoma Cell Line (HepG2) in the Presence and Absence of Zinc]]>https://www.eurekaselect.comarticle/103752Background: Amygdalin (Vitamin B-17) is a naturally occurring vitamin found in the seeds of the fruits of Prunus Rosacea family including apricot, bitter almond, cherry, and peach.

Objective: The purpose of this study was to examine the effect of amygdalin with and without zinc on hepatocellular carcinoma (HepG2) cell line.

Methods: MTT assay was used to evaluate the cytotoxicity of amygdalin without zinc, amygdalin + 20μmol zinc, and amygdalin + 800μmol zinc on HepG2 cell lines. The cell cycle distribution assay was determined by flow cytometry. Apoptosis was confirmed by Annexin V-FITC/PI staining assay. Moreover, the pathway of apoptosis was determined by the percentage of change in the mean levels of P53, Bcl2, Bax, cytochrome c, and caspase-3.

Results: Amygdalin without zinc showed strong anti-HepG2 activity. Furthermore, HepG2 cell lines treatment with amygdalin + 20μmol zinc and amygdalin + 800μmol zinc showed a highly significant apoptotic effect than the effect of amygdalin without zinc. Amygdalin treatment induced cell cycle arrest at G2/M and increased the levels of P53, Bax, cytochrome c, and caspase-3 significantly, while it decreased the level of anti-apoptotic Bcl2.

Conclusion: Amygdalin is a natural anti-cancer agent, which can be used for the treatment of hepatocellular carcinoma. It promotes apoptosis via the intrinsic cell death pathway (the mitochondria-initiated pathway) and cell cycle arrest at G/M. The potency of amygdalin in HepG2 treatment increased significantly by the addition of zinc.

]]>
<![CDATA[Clinical Application of Thiopurine Pharmacogenomics in Pediatrics]]>https://www.eurekaselect.comarticle/104964Background: Thiopurine drugs are used for the treatment of pediatric diseases. Inter-individual differences in the metabolism of these drugs greatly influence the risk of thiopurine induced toxicity and therapy failure. These differences are the consequence of genomic, epigenomic and transcriptomic variability among patients. Pharmacogenomics aims to individualize therapy according to the specific genetic signature of a patient. Treatment protocols based on thiopurine drugs have already been improved by applying pharmacogenomics in pediatric clinical practice.

Objective: The aim of this review was to summarize the application of thiopurine pharmacogenomics in pediatric patients suffering from acute leukemias, different types of autoimmune and inflammatory diseases, as well as in posttransplant care.

Methods: We searched PubMed/Medline database to identify thiopurine pharmacogenomic markers clinically relevant in pediatric diseases.

Results: TPMT and NUDT15 pharmacogenomic testing is done in pediatric care, contributing to the reduction of thiopurine induced toxicity. Data on numerous novel potential pharmacogenomic markers relevant for optimization of thiopurine treatment are still controversial (ITPA, ABCC4, NT5C2, PRPS1, GSTM1, FTO gene variants). Majority of evidences regarding thiopurine pharmacogenomics in pediatrics have been acquired by studying acute lymphoblastic leukemia and inflammatory bowel disease. For other pediatric diseases, namely acute myeloid leukemia, non-Hodgkin lymphoma, juvenile idiopathic arthritis, atopic dermatitis, juvenile autoimmune hepatitis and renal allograft transplantation, data are still scarce.

Conclusion: Thiopurine pharmacogenomics has shown to be one of the best examples of successful application of pharmacogenomics in pediatrics.

]]>
<![CDATA[Lipid-based Nanoplatforms in Cancer Therapy: Recent Advances and Applications]]>https://www.eurekaselect.comarticle/103666 <![CDATA[Targeting Proliferating Cell Nuclear Antigen (PCNA) as an Effective Strategy to Inhibit Tumor Cell Proliferation]]>https://www.eurekaselect.comarticle/103670 <![CDATA[Structural and Bioactive Studies of Halogenated Constituents from Sponges]]>https://www.eurekaselect.comarticle/94418 <![CDATA[Benzofuran: A Key Heterocycle - Ring Closure And Beyond]]>https://www.eurekaselect.comarticle/99533 <![CDATA[Mutation Analysis of ABL1 Gene and its Relation to the Achievement of Major Molecular Response in Indonesian Chronic Myeloid Leukemia Patients]]>https://www.eurekaselect.comarticle/100995Background: Imatinib mesylate is the first tyrosine kinase inhibitor approved for chronic myeloid leukemia (CML) therapy. Imatinib is an effective drug. However, previous studies have shown that about 20-30% of patients eventually would develop resistance to imatinib. Approximately 40% of imatinib resistance is associated with BCRABL kinase domain mutation. One of the most common and serious variations account for imatinib response is T315I of ABL1 gene.

Objective: The study aimed to examine the association of T315I mutation with the ABL1 gene and its relation to major molecular response (MMR) achievement in CML patients. This study also examined other mutations adjacent to T315I, i.e., F311I, F317L, and different possible variations in the ABL1 gene.

Methods: This was a cross-sectional study on Indonesian CML patients in chronic phase. We analyzed 120 blood samples from patients in chronic phase who have received imatinib mesylate (IM) for ≥12 months.

Results: There were no T315I, F311I, and F317L mutations found in this study. However, we found another variation, which was 36 substitutions from A to G at position 163816 of ABL1 gene (according to NG_012034.1).

Conclusion: We found no T315I, F311I, and F317L mutations in this study. Our findings suggest that there might be other factors that influenced the MMR achievement in our study patients. However, there were 36 substitutions from A to G at position 163.816 (according to NG_012034.1) that needed further examination to explore the significance of this mutation in clinical practice.

]]>
<![CDATA[Pharmacokinetics and Systems Pharmacology of Anti-CD47 Macrophage Immune Checkpoint Inhibitor Hu5F9-G4]]>https://www.eurekaselect.comarticle/100334Background: Hu5F9-G4, a human immunoglobulin G4 (IgG4) monoclonal antibody (mAb) has recently been granted fast-track designation by the FDA for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma. Hu5F9-G4 has the ability to block CD47-SIRPα signaling along with anti- EGFR and anti-PD-L1 immune checkpoint activity that is involved in a variety of cancers like solid tumors, Non-Hodgkin’s Lymphoma (NHL), colorectal cancer (CRC), breast, ovarian and bladder cancers, and hematological malignancies. Thus, Hu5F9-G4 is an important biologic that has increasing clinical relevance in cancer care.

Methods: We queried PubMed, Web of Science, Google Scholar, Science Direct and Scopus databases with keywords pertaining to Hu5F9-G4. In addition, we have included the Hu5F9-G4 data presented at the 60th American Society of Hematology (ASH) Annual Meeting, the American Society of Clinical Oncology (ASCO) Annual Meeting and 23rd Congress of the European Hematology Association (EHA).

Results: We discuss the mechanistic basis and preclinical evidence for the anticancer activity of Hu5F9-G4. Further, we delineate clinical studies, alone and in combination with anti-CD20 mAb rituximab, anti-EGFR mAb cetuximab, PD-L1 checkpoint inhibitors avelumab and atezolizumab, and anti-HER2 mAb trastuzumab. Moreover, the potential adverse effects, pharmacokinetics, and pharmacodynamics of Hu5F9-G4 with emphasis on the role of CD47-SIRPα signaling in phagocytosis are presented.

Conclusion: Taken together, we review the pharmacokinetics and systems pharmacology of Hu5F9-G4 which appears to hold great promise for the future of cancer care.

]]>
<![CDATA[Evaluation of Anticancer Activities of Gallic Acid and Tartaric Acid Vectorized on Iron Oxide Nanoparticles]]>https://www.eurekaselect.comarticle/100619

Objective: Super paramagnetic nanoparticle serves as drug carrier for drug delivery system. Herein, Iron oxide-CMC-TA and Iron oxide-CMC-GA nanoparticles are synthesized for this target.

Methods: Iron oxide (Fe2O3) nanoparticles are synthesized, bound to carboxymethyl chitosan (CMC) which are then conjugated to tartaric acid (TA) or gallic acid (GA) to form Iron oxide-CMC-TA and Iron oxide-CMC-GA nanoparticles. Those nanoparticles were characterized and the cytotoxicity effect was evaluated when associated with/without bee venom to measure the synergistic effect on A549 and WI-38 cell lines. In addition, apoptotic genes expression in A549 was evaluated when treated with both nanoparticles.

Results: We showed that the cytotoxicity effect of TA and GA on A549 and WI-38 cell lines was increased when they immobilized on iron oxide-CMC nanoparticles and the effect was synergistically elevated when added to bee venom. The cytotoxic activity of these two nanoparticles was higher in A549 cancer cell line when compared with WI-38 normal cell line. Moreover, the expression of apoptotic genes was elevated.

Conclusion: Iron oxide-CMC-TA nanoparticle and Iron oxide-CMC-GA nanoparticle can selectively induce apoptosis in cancer cell lines more than in normal cell lines, which is an important aspect in cancer cell targeting process to minimize damage upon normal cells.]]>
<![CDATA[The Close Interplay of Nitro-Oxidative Stress, Advanced Glycation end Products and Inflammation in Inflammatory Bowel Diseases]]>https://www.eurekaselect.comarticle/92805

Methods: We searched the PubMed, ScienceDirect and Web of Science databases using a combination of the following terms: IBD, CRC, oxidative stress, inflammation, NF-κB, Nrf2, p53M, AGE and RAGE.

Results: Oxidative stress and inflammation activated two cellular pathways, the nuclear expression of pro-inflammatory, pro-oxidant and pro-oncogenic genes based on NF-κB and p53M, which is associated with NF-κB activation, Deoxyribonucleic acid (DNA) damage and the expression of pro-oncogenic genes. Nrf2 stimulates the nuclear expression of enzymatic and non-enzymatic antioxidant systems and anti-inflammatory genes, and is inhibited by chronic oxidative stress, NF-κB and p53M. AGE/RAGE are involved in inflammation progression because RAGE polymorphisms and increased RAGE levels are found in IBD patients. Alterations of these pathways in combination with oxidative damage are responsible for IBD symptoms and the progression to CRC.

Conclusion: IBD is an inflammatory and nitro-oxidative stress-based bowel disease. Achieving a molecular understanding of the biochemical events and their complicated interactions will impact basic and applied research, animal models, and clinical trials.]]>
<![CDATA[Role of Pro-inflammatory Cytokines in Regulation of Skeletal Muscle Metabolism: A Systematic Review]]>https://www.eurekaselect.comarticle/94873

Objective: This review will discuss the role of pro-inflammatory cytokines in skeletal muscles during muscle wasting conditions. Moreover, the coordination among the pro-inflammatory cytokines and their regulated molecular signaling pathways which increase the protein degradation will be discussed.

Results: During normal conditions, pro-inflammatory cytokines are required to balance anabolism and catabolism and to maintain normal myogenesis process. However, during muscle wasting their enhanced expression leads to marked destructive metabolism in the skeletal muscles. Proinflammatory cytokines primarily exert their effects by increasing the expression of calpains and E3 ligases as well as of Nf-κB, required for protein breakdown and local inflammation. Proinflammatory cytokines also locally suppress the IGF-1and insulin functions, hence increase the FoxO activation and decrease the Akt function, the central point of carbohydrates lipid and protein metabolism.

Conclusion: Current advancements have revealed that the muscle mass loss during skeletal muscular atrophy is multifactorial. Despite great efforts, not even a single FDA approved drug is available in the market. It indicates the well-organized coordination among the pro-inflammatory cytokines that need to be further understood and explored.]]>
<![CDATA[Anticancer Potential of Dietary Natural Products: A Comprehensive Review]]>https://www.eurekaselect.comarticle/101453 <![CDATA[Bioactive Secondary Metabolites from Endophytic Fungi]]>https://www.eurekaselect.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[Factors Affecting the Metabolite Productions in Endophytes: Biotechnological Approaches for Production of Metabolites]]>https://www.eurekaselect.comarticle/99238 <![CDATA[The Role and Mechanism of Thiol-Dependent Antioxidant System in Bacterial Drug Susceptibility and Resistance]]>https://www.eurekaselect.comarticle/98608 <![CDATA[Anthocyanins As Modulators of Cell Redox-Dependent Pathways in Non-Communicable Diseases]]>https://www.eurekaselect.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.

]]>
<![CDATA[Kinetic Evaluation of Anti-tumor Chlorambucil Release from O-stearoyl Mannose PLGA Nanoparticles]]>https://www.eurekaselect.comarticle/100439Purpose: This study assesses the kinetics of the anti-tumor drug chlorambucil (CLB) incorporated into PLGA nanoparticles (NP-CLB) with and without the presence of the O-stearoyl mannose (OEM) functionalizing agent (NP-CLBMAN).

Methods: OEM was synthesized and used in the NP-CLB-MAN formulation. The nanoparticles were characterized by dynamic light scattering, electrophoretic light scattering, scanning electron microscopy, and Fourier-transform infrared spectroscopy.

Results: The nanoparticles presented an encapsulation efficiency greater than 61% and a PdI between 0.186–0.217. The mean size was 185 nm for NP-CLB and 220 nm for NPCLB- MAN, and the zeta potential values were -17.7 mV for NP-CLB and -14.2 mV for NP- CLB-MAN. Scanning electron microscopy showed that NPs with OEM have a surface with a different shape, and FTIR analyses showed binding of CLB to the drug delivery system, as well as functionalization with OEM. In vitro release studies showed a biphasic release profile for both systems, and they were analyzed considering the mathematical Korsmeyer-Peppas, first-order, and Fick diffusion models, and the combination of the first-order and Fick diffusion models.

Conclusion: The experimental results obtained for the release of CLB were better described using a combination of the first order and Fick diffusion mathematical models.

]]>
<![CDATA[Dietary Phenolic Acids and Flavonoids as Potential Anti-Cancer Agents: Current State of the Art and Future Perspectives]]>https://www.eurekaselect.comarticle/101657Background: Cancer is a rapidly growing disease and the second most leading cause of death worldwide. Breast, colon, lung, and prostate cancer are the most diagnosed types of cancer among the majority of the population. The prevalence of these cancers is increasing rapidly due to the lack of effective drugs. The search for anti-cancer bioactive components from natural plant sources is gaining immense significance. The aim of the paper is to introduce the readers about the in vitro and in vivo biochemical mechanisms of phenolic acids and flavonoids in these four types of cancers.

Methods: A literature search was carried out in databases, including Scopus, SciFinder, Springer, Science direct and Google. The main keywords used were fruits & vegetables, phenolic acids, flavonoids, anticancer, bioavailability, etc. The data obtained were integrated and analyzed.

Results: The study revealed the potential molecular mechanisms of phenolic acids and flavonoids, which include the induction of apoptosis, inhibition of cell proliferation, cell-cycle arrest, induction of Poly ADP ribose polymerase cleavage, downregulation of Matrix metalloproteinases-2 and Matrix metalloproteinases-9 activities, decreased levels of B-cell lymphoma-2, etc. Promising effects of phenolic acids and flavonoids have been observed against breast, colon, lung and prostate cancers.

Conclusion: The in vitro and in vivo anti-cancer mechanisms of phenolic acids and flavonoids have been revealed in this study. With the knowledge of specific molecular targets and the structural-functional relationship of bioactive compounds, the current review will open a new gateway for the scientific community and provide them a viable option to exploit more of these compounds for the development of novel and efficacious anticancer compounds.

]]>
<![CDATA[Molecular Docking Study, Cytotoxicity, Cell Cycle Arrest and Apoptotic Induction of Novel Chalcones Incorporating Thiadiazolyl Isoquinoline in Cervical Cancer]]>https://www.eurekaselect.comarticle/101862Background: Chalcones are naturally occurring compounds found in various plant species which are widely used for the traditional popular treatments. Chalcones are distinguished secondary metabolites reported to display diverse biological activities such as antiviral, antiplatelet, anti-inflammatory, anticancer, antibacterial and antioxidant. The presence of a,ß-unsaturated carbonyl group in chalcones is assumed to be responsible for their bioactivity. In addition, heterocyclic compounds having nitrogen such as isoquinolines are of considerable interest as they constitute the core structural element of many alkaloids that have enormous pharmacological activities.

Objective: The objective of this study is the synthesis and biological activity of novel chalcones incorporating thiadiazolyl isoquinoline as potential anticancer candidates. Different genetic tools were used in an attempt to know the mechanism of action of this compound against breast cancer.

Methods: An efficient one pot synthesis of novel chalcones incorporating thiadiazolyl isoquinoline was developed. The cytotoxic activity of the novel synthesized compounds was performed against four different kinds of cancer cell lines.

Results: Among all the tested derivatives, chalcone 3 has the best cytotoxic profile against A549, MCF7, and HeLa cell lines, with IC50s values 66.1, 51.3, and 85.1μM, respectively. Molecular docking studies for chalcone 3 revealed that CDK2, and EGFRTK domains have strong binding affinities toward the novel chalcone 3, while tubulin-colchicine-ustiloxin, and VEGFRTK domains illustrated moderate mode of binding.

Conclusion: We have developed an efficient method for the synthesis of novel chalcones incorporating thiadiazolyl isoquinoline. All compounds showed better cytotoxicity results against four kinds of cancer cell lines (A549, MCF7, HCT116, and HELA cells). The results depicted that chalcone 3 has a high and promising cytotoxic effect against HELA cell line and the mechanism of cytotoxicity was widely studied through different theoretical and experimental tools. Thus, the newly synthesized derivative 3 can be utilized as a novel chemotherapeutic compound for cervical carcinoma.

]]>
<![CDATA[Marine Natural Products with High Anticancer Activities]]>https://www.eurekaselect.comarticle/103621 <![CDATA[Carbohydrates: Potential Sweet Tools Against Cancer]]>https://www.eurekaselect.comarticle/91819Cancer, one of the most devastating degenerative diseases nowadays, is one of the main targets in Medicinal Chemistry and Pharmaceutical industry. Due to the significant increase in the incidence of cancer within world population, together with the complexity of such disease, featured with a multifactorial nature, access to new drugs targeting different biological targets connected to cancer is highly necessary.

Among the vast arsenal of compounds exhibiting antitumor activities, this review will cover the use of carbohydrate derivatives as privileged scaffolds. Their hydrophilic nature, together with their capacity of establishing selective interactions with biological receptors located on cell surface, involved in cell-to-cell communication processes, has allowed the development of an ample number of new templates useful in cancer treatment.

Their intrinsic water solubility has allowed their use as of pro-drug carriers for accessing more efficiently the pharmaceutical targets. The preparation of glycoconjugates in which the carbohydrate is tethered to a pharmacophore has also allowed a better permeation of the drug through cellular membranes, in which selective interactions with the carbohydrate motifs are involved. In this context, the design of multivalent structures (e.g. gold nanoparticles) has been demonstrated to enhance crucial interactions with biological receptors like lectins, glycoproteins that can be involved in cancer progression.

Moreover, the modification of the carbohydrate structural motif, by incorporation of metal complexes, or by replacing their endocyclic oxygen, or carbon atoms with heteroatoms has led to new antitumor agents.

Such diversity of sugar-based templates with relevant antitumor activity will be covered in this review.

]]>
<![CDATA[Recent Advances in Peptide-Based Approaches for Cancer Treatment]]>https://www.eurekaselect.comarticle/87083Background: Peptide-based pharmaceuticals have recently experienced a renaissance due to their ability to fill the gap between the two main classes of available drugs, small molecules and biologics. Peptides combine the high potency and selectivity typical of large proteins with some of the characteristic advantages of small molecules such as synthetic accessibility, stability and the potential of oral bioavailability.

Methods: In the present manuscript we review the recent literature on selected peptide-based approaches for cancer treatment, emphasizing recent advances, advantages and challenges of each strategy.

Results: One of the applications in which peptide-based approaches have grown rapidly is cancer therapy, with a focus on new and established targets. We describe, with selected examples, some of the novel peptide-based methods for cancer treatment that have been developed in the last few years, ranging from naturally-occurring and modified peptides to peptidedrug conjugates, peptide nanomaterials and peptide-based vaccines.

Conclusion: This review brings out the emerging role of peptide-based strategies in oncology research, critically analyzing the advantages and limitations of these approaches and the potential for their development as effective anti-cancer therapies.

]]>