<![CDATA[Retinoblastoma]]> https://www.eurekaselect.com RSS Feed for Disease Wise Article | BenthamScience EurekaSelect (+http://eurekaselect.com) Thu, 28 Mar 2024 08:10:13 +0000 <![CDATA[Retinoblastoma]]> https://www.eurekaselect.com https://www.eurekaselect.com <![CDATA[Analysis of Codon Usage Patterns in the Human Papillomavirus Oncogenes]]>https://www.eurekaselect.comarticle/107346Background: Persistent high-risk genital human papillomavirus (HPV) infection is a major cause of cervical cancer in women. The products of the viral transforming genes E6 and E7 in the high-risk HPVs are known to be similar in their amino acid composition and structure. We performed a comparative analysis of codon usage patterns in the E6 and E7 genes of HPVs.

Methods: The E6 and E7 gene sequences of eight HPV subtypes were analyzed to determine their nucleotide composition, relative synonymous codon usage (RSCU), effective number of codons (ENC), neutrality, genetic variability, selection pressure, and codon adaptation index (CAI). Additionally, a correspondence analysis (CoA) was performed.

Results: The analysis to determine the effects of differences in composition on the codon usage patterns revealed that there might be usage bias for ‘A’ nucleotides. This was consistent with the results of the RSCU analysis, which demonstrated that the selection of A/T-rich patterns and the preference for A/T-ended codons in HPVs are influenced by compositional constraints. Moreover, the results reveal that selection pressure plays an important role in the CoA results for the RSCU values, Tajima’s D tests, and neutrality tests.

Conclusion: The results of this study are consistent with previous findings that most papillomavirus genes are under purifying selection pressure, which limits changes to the encoded proteins. Natural selection and mutation pressures resulting in changes in the nucleotide composition and codon usage bias in the two tumor genes of HPV act differently during the evolution of the HPV subtype; thus, throughout the viral life cycle, HPV can constantly evolve to adapt to a new environment.

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<![CDATA[Circular RNAs and Glioma: Small Molecule with Big Actions]]>https://www.eurekaselect.comarticle/107243 <![CDATA[MiR-492 as an Important Biomarker for Early Diagnosis and Targeted Treatment in Different Cancers]]>https://www.eurekaselect.comarticle/105085 <![CDATA[Cancer Stem Cells with Overexpression of Neuronal Markers Enhance Chemoresistance and Invasion in Retinoblastoma]]>https://www.eurekaselect.comarticle/106334Background: Retinoblastoma is a sight and life-threatening embryonal tumor in children. Though chemotherapy is the main mode of therapy, evolving resistance remains a major obstacle in treatment success. The presence of cancer stem cells (CSC) is frequently reported to be responsible for chemoresistance in multiple tumors.

Objective: Our study aims to identify the molecular factors that facilitate the chemoresistance through cancer stem cells in retinoblastoma.

Methods: We developed etoposide and carboplatin resistant retinoblastoma (Y79) cell lines by stepwise drug increment treatment, validated with MTT and TUNEL assays. Colony forming and invasive ability were studied by soft-agar colony forming and transwell assays, respectively. Similar analysis in non-responsive retinoblastoma tumors were carried out by histopathology. Finally, expression of CSC/neuronal markers and ABC transporters were examined by quantitative PCR and protein expression of neuronal stem cell markers was confirmed by Western blot.

Results: Larger colony size of resistant cells in soft-agar assay provided evidence for increased selfrenewability. Histopathology in non-responsive tumors showed poorly differentiated cells predominantly. Besides, both resistant cell lines and non-responsive tumors showed increased invasion with higher expression of neuronal stem cell markers - SOX2, NANOG, OCT4 and ABC transporters - ABCB1 and ABCC3. Increased self-renewal ability and invasion along with overexpression of stemness markers in resistant cells and tumors provide evidence for stemness driving chemoresistance and invasion in retinoblastoma.

Conclusion: We have demonstrated Neuronal stem cell/CSC markers that facilitate the maintenance of cancer stem cells. Developing therapies targeting these factors will help in overcoming resistance and improving retinoblastoma treatment.

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<![CDATA[Aptamer-Based Targeted Drug Delivery Systems: Current Potential and Challenges]]>https://www.eurekaselect.comarticle/93502 <![CDATA[Anticancer Potential of Dietary Natural Products: A Comprehensive Review]]>https://www.eurekaselect.comarticle/101453 <![CDATA[MicroRNAs Determining Carcinogenesis by Regulating Oncogenes and Tumor Suppressor Genes During Cell Cycle]]>https://www.eurekaselect.comarticle/100920Aim: To provide a review considering microRNAs regulating oncogenes and tumor suppressor genes during the different stages of cell cycle, controlling carcinogenesis.

Methods: The role of microRNAs involved as oncogenes’ and tumor suppressor genes’ regulators in cancer was searched in the relevant available literature in MEDLINE, including terms such as “microRNA”, “oncogenes”, “tumor suppressor genes”, “metastasis”, “cancer” and others.

Results: MicroRNAs determine the expression levels of multiple cell cycle regulators, such as cyclins, cyclin dependent kinases and other major cell cycle activators including retinoblastoma 1 (RB- 1) and p53, resulting in alteration and promotion/inhibition of the cell cycle.

Conclusion: MicroRNAs are proven to have a key role in cancer pathophysiology by altering the expression profile of different regulator proteins during cell division cycle and DNA replication. Thus, by acting as oncogenes and tumor suppressor genes, they can either promote or inhibit cancer development and formation, revealing their innovative role as biomarkers and therapeutic tools.

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<![CDATA[Synthesis, Biological Evaluation and Molecular Dynamics Simulation Studies of Novel Diphenyl Ethers]]>https://www.eurekaselect.comarticle/97106Background: The well-known antibacterial agent Triclosan (TCL) that targets bacterial enoylacyl protein reductase has been described to inhibit human fatty acid synthase (FASN) via the enoylacyl reductase domain. A Literature survey indicates that TCL is selectively toxic to cancer cells and furthermore might indeed reduce cancer incidence in vivo. A recent study found that TCL inhibits FASN by acting as an allosteric protein-protein interface (PPI) inhibitor. It induces dimer orientation changes that effect in a downstream reorientation of catalytic residues in the NADPH binding site proposing TCL as a viable scaffold to design a superior molecule that might have more inhibitory potential. This unveils tons of potential interaction space to take advantage of future inhibitor design.

Objectives: Synthesis of TCL mimicking novel diphenyl ether derivatives, biological evaluation as potential antiproliferative agents and molecular docking and molecular dynamics simulation studies.

Methods: A series of novel N-(1-(3-hydroxy-4-phenoxyphenyl)-3-oxo-3-phenylpropyl)acetamides (3a-n) and N-(3(3-hydroxy-4phenoxyphenyl)-3-oxo-1-phenylpropyl) acetamides (6a-n) were designed, synthesized, characterized and evaluated against HepG2, A-549, MCF-7 and Vero cell lines. The induction of antiproliferative activity of selected compounds (3d and 6c) was done by AO/EB (acridine orange/ethidium bromide) nuclear staining method, DNA fragmentation study, and cell cycle analysis was performed by flow cytometry. Molecular docking and dynamics simulation study was also performed.

Results: Among the tested compounds, compound 3d was most active (IC50 13.76 ± 0.43 µM) against A-549 cell line. Compounds 3d and 3g were found to be moderately active with IC50 30.56 ± 1.1 µM and 25.05 ± 0.8 µM respectively against MCF-7 cell line. Morphological analysis of A-549 cells treated with 3d and 6c clearly demonstrated the reduction of cell viability and induction of apoptosis. DNA fragmentation was observed as a characteristic of apoptosis in treated cells. Further, cell cycle analysis by flow cytometry confirmed that compounds 3d and 6c significantly arrested the cell cycle at the G0/G1 phase. Molecular docking study demonstrated that these compounds exhibit high affinity for the human fatty acid synthase (hFASN) target. Molecular dynamics simulation study of the most active compound 3d was performed for calculating binding free energies using Molecular Mechanics–Generalized Born Surface Area (MM/GBSA).

Conclusion: Compound 3d (IC50 13.76 ± 0.43 µM) has been identified as a potential lead molecule for anticancer activity against A-549 cells followed by 3l, 6c, and 3g. Thus, the design of diphenyl ether derivatives with enhanced affinity to the binding site of hER may lead to the discovery of potential anticancer agents.

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<![CDATA[New Entrants into Clinical Trials for Targeted Therapy of Breast Cancer: An Insight]]>https://www.eurekaselect.comarticle/101637 <![CDATA[The Cancer Hygiene Hypothesis: From Theory to Therapeutic Helminths]]>https://www.eurekaselect.comarticle/93401

Materials & Methods: Research and online content related to cancer hygiene hypothesis is highlighted and to illustrate key themes. Guidelines for meaningful participation in DOC activities for people with diabetes, families, health care providers, and industry are provided.

Results: The lack of worms leads to failure of stimulation of mucosal Th2 responses. These infections exert their effect through critically altering T-helper (Th)1/Th2 regulation, and it is postulated that, thus, they protect against atopy and asthma, through the induction of Th1 regulatory response. It is now also recognized that this “hygiene hypothesis” concept applies to a wider range of chronic inflammatory diseases than atopy and asthma, such as diabetes, multiple sclerosis and cancer.

Conclusion: Here we discuss the major implications of these findings for the association between microorganisms and cancer, and also between some immune pathologies, like autoimmune diseases, and cancer.

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<![CDATA[Immunology Behind Tumors: A Mini Review]]>https://www.eurekaselect.comarticle/92872

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

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<![CDATA[The Molecular Pathology of Eye Tumors: A 2019 Update Main Interests for Routine Clinical Practice]]>https://www.eurekaselect.comarticle/99994 <![CDATA[Novel Target Sites for Drug Screening: A Special Reference to Cancer, Rheumatoid Arthritis and Parkinson’s Disease]]>https://www.eurekaselect.comarticle/89189Background: The humans can be affected by more than 100 types of cancers in which about 22 % cancer death are caused by tobacco, 10% due to alcohol and obesity, 5-10 % by genetic defects and 20 % by infections. Rheumatoid arthritis, an autoimmune disorder, occurs mostly in middle age, affects 2.5 times more to females than males and till 2015, more than 24.5 Million people get affected from this disorder. The deaths due to rheumatoid arthritis were 28000 in 1990 and increased to 38000 in 2013. Parkinson’s disease, a neurodegenerative disorder of central nervous system affects about 6.2 million people in 2015 and responsible for approximately 117400 deaths worldwide. Parkinson’s disease occurs mainly over the age of 60 and males get more affected than females.

Methods: Bibliographic database has created by mendeley desktop software for available literature in peer reviewed research articles especially by titles and disease names as keywords with AND Boolean operator (title AND year or author AND year). The intervention and findings of quality papers were extracted by detailed study and a conceptual framework has developed.

Results: Total 121 research and review articles are cited in this review to produce high impact in literature for pathophysiology and receptors involved in all three diseases. Changes in enzyme action, prohibition of angiogenesis and inhibition of microtubule are the main areas where anticancer molecules may perform significant effect. The immune system is not a good target for rheumatic treatment due to many complications that occur in body but fibroblast, like synoviocytes, proteases which are responsible for cartilage destruction and osteoclast differentiation may be the beneficial targets for pharmacoactive molecules in the treatment of rheumatoid arthritis. In Parkinson’s disease, supply of dopamine to brain from outside results in brain dopamine synthesis decrement which increase drug dependency. The compounds which stimulate secretion, reuptake inhibitor and increment in dopaminergic neurons may be good targets.

Conclusion: Alteration of signal transduction by a drug is the goal of chemogenomics, a new branch formed by combination of chemistry and genomics. The proliferation, angiogenesis and apoptosis of cancer cells are regulated by cellular signaling of transcription factors, protein kinases, transmembrane receptors, extracellular ligands and some external factors like oncogenic mutations, ubiquitin-proteasome pathway with epigenetic changes. Traditional anticancer drugs either alter DNA synthesis or control cell division while new drugs retard tumor growth or induce apoptosis. The deterioration of dopaminergic neurons in substantia nigra results in Parkinson’s disease with mental confusion, cognitive dysfunction and sleep disorder. Rheumatoid arthritis is characterized by inflammation, autoimmunity, joint destruction, deformity and premature mortality and treated mainly by anti-inflammatory and antirheumatic drugs. This review provides a comprehensive summary of objects which may act as potential targets for many health disorders.

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<![CDATA[Drug Repurposing for Retinoblastoma: Recent Advances]]>https://www.eurekaselect.comarticle/95947 <![CDATA[Overcoming Antibiotic Resistance: Insights from Clostridium difficile and the RB Tumor Suppressor]]>https://www.eurekaselect.comarticle/100722 <![CDATA[Targeted Therapies for Autosomal Dominant Polycystic Kidney Disease]]>https://www.eurekaselect.comarticle/90250Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common life-threatening genetic disease in humans, affecting approximately 1 in 500 people. ADPKD is characterized by cyst growth in the kidney leading to progressive parenchymal damage and is the underlying pathology in approximately 10% of patients requiring hemodialysis or transplantation for end-stage kidney disease. The two proteins that are mutated in ADPKD, polycystin-1 and polycystin-2, form a complex located on the primary cilium and the plasma membrane to facilitate calcium ion release in the cell. There is currently no Food and Drug Administration (FDA)-approved therapy to cure or slow the progression of the disease. Rodent ADPKD models do not completely mimic the human disease, and therefore preclinical results have not always successfully translated to the clinic. Moreover, the toxicity of many of these potential therapies has led to patient withdrawals from clinical trials.

Results: Here, we review compounds in clinical trial for treating ADPKD, and we examine the feasibility of using a kidney-targeted approach, with potential for broadening the therapeutic window, decreasing treatment-associated toxicity and increasing the efficacy of agents that have demonstrated activity in animal models. We make recommendations for integrating kidney- targeted therapies with current treatment regimes, to achieve a combined approach to treating ADPKD.

Conclusion: Many compounds are currently in clinical trial for ADPKD yet, to date, none are FDA-approved for treating this disease. Patients could benefit from efficacious pharmacotherapy, especially if it can be kidney-targeted, and intensive efforts continue to be focused on this goal.

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<![CDATA[Anti-tumor Drug Targets Analysis: Current Insight and Future Prospect ]]>https://www.eurekaselect.comarticle/97752 <![CDATA[Targeting p53-MDM2 Interaction Using Small Molecule Inhibitors and the Challenges Needed to be Addressed ]]>https://www.eurekaselect.comarticle/97747 <![CDATA[Interactions of Vascular Endothelial Growth Factor and p53 with miR-195 in Thyroid Carcinoma: Possible Therapeutic Targets in Aggressive Thyroid Cancers]]>https://www.eurekaselect.comarticle/91339Background: The clinical pathological features, as well as the cellular mechanisms of miR-195, have not been investigated in thyroid carcinoma.

Objective: The aim of this study is to identify the interactions of vascular endothelial growth factor (VEGF), p53 and miR-195 in thyroid carcinoma. The clinical and pathological features of miR-195 were also investigated.

Methods: The expression levels of miR-195 were identified in 123 primary thyroid carcinomas, 40 lymph nodes with metastatic papillary thyroid carcinomas and seven non-neoplastic thyroid tissues (controls) as well as two thyroid carcinoma cell lines, B-CPAP (from metastasizing human papillary thyroid carcinoma) and MB-1 (from anaplastic thyroid carcinoma), by the real-time polymerase chain reaction. Using Western blot and immunofluorescence, the effects of exogenous miR-195 on VEGF-A and p53 protein expression levels were examined. Then, cell cycle and apoptosis assays were performed to evaluate the roles of miR-195 in cell cycle progression and apoptosis.

Results: The expression of miR-195 was downregulated in majority of the papillary thyroid carcinoma tissue as well as in cells. Introduction of exogenous miR-195 resulted in downregulation of VEGF-A and upregulation of p53 protein expressions. Upregulation of miR-195 in thyroid carcinoma cells resulted in cell cycle arrest. Moreover, we demonstrated that miR-195 inhibits cell cycle progression by induction of apoptosis in the thyroid carcinoma cells.

Conclusion: Our findings showed for the first time that miR-195 acts as a tumour suppressor and regulates cell cycle progression and apoptosis by targeting VEGF-A and p53 in thyroid carcinoma. The current study exhibited that miR-195 might represent a potential therapeutic target for patients with thyroid carcinomas having aggressive clinical behaviour.

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<![CDATA[A Review on Important Histone Acetyltransferase (HAT) Enzymes as Targets for Cancer Therapy]]>https://www.eurekaselect.comarticle/91860 <![CDATA[Targeting Nodal and Cripto-1: Perspectives Inside Dual Potential Theranostic Cancer Biomarkers]]>https://www.eurekaselect.comarticle/92984Background: Elucidating the mechanisms of recurrence of embryonic signaling pathways in tumorigenesis has led to the discovery of onco-fetal players which have physiological roles during normal development but result aberrantly re-activated in tumors. In this context, Nodal and Cripto-1 are recognized as onco-developmental factors, which are absent in normal tissues but are overexpressed in several solid tumors where they can serve as theranostic agents.

Objective: To collect, review and discuss the most relevant papers related to the involvement of Nodal and Cripto-1 in the development, progression, recurrence and metastasis of several tumors where they are over-expressed, with a particular attention to their occurrence on the surface of the corresponding sub-populations of cancer stem cells (CSC).

Results: We have gathered, rationalized and discussed the most interesting findings extracted from some 370 papers related to the involvement of Cripto-1 and Nodal in all tumor types where they have been detected. Data demonstrate the clear connection between Nodal and Cripto-1 presence and their multiple oncogenic activities across different tumors. We have also reviewed and highlighted the potential of targeting Nodal, Cripto-1 and the complexes that they form on the surface of tumor cells, especially of CSC, as an innovative approach to detect and suppress tumors with molecules that block one or more mechanisms that they regulate.

Conclusion: Overall, Nodal and Cripto-1 represent two innovative and effective biomarkers for developing potential theranostic anti-tumor agents that target normal as well as CSC subpopulations and overcome both pharmacological resistance and tumor relapse.

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<![CDATA[Nitrogen Mustards as Anticancer Chemotherapies: Historic Perspective, Current Developments and Future Trends]]>https://www.eurekaselect.comarticle/97704 <![CDATA[Breaking the DNA Damage Response via Serine/Threonine Kinase Inhibitors to Improve Cancer Treatment]]>https://www.eurekaselect.comarticle/87987 <![CDATA[Implications of Fibroblast Growth Factors (FGFs) in Cancer: From Prognostic to Therapeutic Applications]]>https://www.eurekaselect.comarticle/95747 <![CDATA[Hybrid Magnetic Nanostructures For Cancer Diagnosis And Therapy]]>https://www.eurekaselect.comarticle/94389 <![CDATA[Antiproliferative Activity of microRNA-125a and its Molecular Targets]]>https://www.eurekaselect.comarticle/94268Background: MicroRNA-125a is present in all animals with bilateral symmetry and displays a conserved nucleotide sequence with a section of 11 bases including the seed region that is identical in all considered species. It primarily downregulates the expression of LIN28, thereby promoting cell differentiation and larval phase transitions in nematodes, mammals and insects.

Objective: In this review, we focus on the cellular control of miR-125a expression and its antiproliferative activity.

Results: In mammalians, microRNA-125a is present in most adult organs and tissues in which it targets proteins involved in the mitogenic response, such as membrane receptors, intracellular signal transducers, or transcription factors, with the overall effect of inhibiting cell proliferation. Tissue levels of miR-125a generally raise during differentiation but it is often downregulated in cancers, e.g. colon, cervical, gastric, ovarian, lung, and breast cancers, osteosarcoma, neuroblastoma, glioblastoma, medulloblastoma, retinoblastoma and hepatocellular carcinoma.

Conclusion: The antiproliferative activity of miR-125a, demonstrated in many cell types, together with the notion that this miRNA is downregulated in several kinds of cancers, give a substantial support to the concept that miR-125a plays an oncosuppressive role.

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<![CDATA[Amino Acid Degrading Enzymes and their Application in Cancer Therapy]]>https://www.eurekaselect.comarticle/86240

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

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

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

Conclusion: The findings of this review revealed that therapy based on amino acid depletion may have the potential application for cancer treatment but further clinical investigations are required to provide the efficacy and safety of these agents.]]> <![CDATA[Molecular Studies on Novel Antitumor Bis 1,4-Dihydropyridine Derivatives Against Lung Carcinoma and their Limited Side Effects on Normal Melanocytes]]>https://www.eurekaselect.comarticle/93826

Objective: The objective of this study is the synthesis of bis 1,4-DHPs incorporating ester as well as ether linkages and evaluate the anticancer activity of new compounds for synergistic purpose. Different genetic tools were used in an attempt to know the mechanism of action of this compound against lung cancer.

Method: An efficient one pot synthesis of bis 1,4-DHPs using 3-aminocrotononitrile and bis(aldehydes) has been developed. The cytotoxic effect against human cell lines MCF7, and A549 cell lines was evaluated.

Results: All compounds exhibited better cytotoxicity toward lung carcinoma cells than breast cancer cells. With respect to lung carcinoma cell line (A549), compound 10 was the most active compound and the three other compounds 7, 8, and 9 showed comparable IC50 values. In case of breast cancer cell line (MCF7), the most active one was compound 7, while compound 8 recorded the least activity.

Conclusion: we have developed an efficient method for the synthesis of novel bis 1,4-dihydropyridine derivatives incorporating ester or ether linkage. All compounds showed better cytotoxicity results against A549 than MCF7, so that lung carcinoma cell line was chosen to perform the molecular studies on it. The results showed that all compounds (7, 8, 9 and 10) caused cell cycle arrest at G1 phase. The molecular docking study on CDK2 confirmed the results of cell cycle assay which showed good binding energy between the compounds and the active site of enzyme indicating the inhibition of the enzyme.]]> <![CDATA[Silimarin and Cancer]]>https://www.eurekaselect.comarticle/92846

Methods: Silimarin has been demonstrated to “inhibit cell proliferation and to induce apoptosis, while also having anti-angiogenic properties.” The induction of apoptosis in cancer cells has been mediated by the involvement of ER stress.

Results: Silibinin has the potential to operate as a STAT3-targeted inhibitor as well as an inhibitor of the upregulation of the immune checkpoint regulator PD-L1 and also EMT regulators, thus being a promising adjuvant in NSCLC. It has also been documented to suppress cancer cells be means of down- regulating actin cytoskeleton and PI3K / Akt molecular pathways. Several studies have demonstrated that silibinin exerts its protective potential partly through interacting with the tumor suppressor gene p53.

Conclusions: It is noteworthy that research has been carried out on the enhancement of silimarin’s bioavailability, especially by the preparation of specific nanoformulas, and its probable additional use together with the chemotherapeutic regimens in the near future.]]> <![CDATA[Critical microRNAs in Lung Cancer: Recent Advances and Potential Applications]]>https://www.eurekaselect.comarticle/92269

Objective: This article reviewed the current knowledge on the role of miRNAs and their target genes in lung cancer and discussed the potential use of some miRNAs as novel therapeutic agents in lung cancer.

Method: Firstly, we collected and summarized all research and review and research articles in databases including Scopus and PubMed. Then, we used related keywords that are important to lung cancer target therapy and their diagnostic and prognostic values.

Results: Based on collected articles and research, recognizing critical microRNA and controlling the expression of this microRNA by antagonist oligonucleotides like antagomiRs or anti-miRs and microRNA mimicking will have a remarkable role in treating lung cancer.

Conclusion: Many research studies have shown that a combination of chemotherapy plus knockdown or mimicking microRNA is effective and useful in the cancers treatment like lung cancer.]]> <![CDATA[Molecular Mechanism of Aniline Induced Spleen Toxicity and Neuron Toxicity in Experimental Rat Exposure: A Review]]>https://www.eurekaselect.comarticle/92176 <![CDATA[Epigenetic Targets and their Inhibitors in Cancer Therapy]]>https://www.eurekaselect.comarticle/95390 <![CDATA[Function Analysis of Human Protein Interactions Based on a Novel Minimal Loop Algorithm]]>https://www.eurekaselect.comarticle/92860

Method: In this paper, we proposed a minimal protein loop finding method to explore the elementary structural motifs of human PPI network. Initially, an improved article exchange model was designed to search all the independent shortest protein loops of PPI network. Furthermore, Gene Ontology (GO) based function clustering analysis was implemented to identify the biological functions of the shortest protein loops. Additionally, the disease process associated shortest protein loops were considered as the potential drug targets.

Result: Our proposed method presents the lowest computational complexity and the highest functional consistency, compared to the three other methods. The functional enrichment and clustering analysis for the identified minimal protein loops revealed the high correlation between the protein loops and the corresponding biological functions, particularly, statistical analysis presenting the protein loops with the length less than 4 is closely connected with some disease process, suggesting the potential drug target.

Conclusion: Our minimal protein loop method provides a novel manner to precisely define the functional motif of PPI network, which extends the current knowledge about the cooperating mechanisms and topological properties of protein modules composed of the short loops.]]> <![CDATA[Sorbinil, an Aldose Reductase Inhibitor, in Fighting Against Diabetic Complications]]>https://www.eurekaselect.comarticle/90641

Objective: In this review article, we have discussed the role of sorbinil, an AR inhibitor (ARI), in preventing diabetic complications.

Results: AR contributes in diabetes by generating excess intracellular superoxide and other mediators of oxidative stress through polyol pathway. Inhibition of AR activity thus might be a potential approach for the management of diabetic complications. Experimental evidences indicated that sorbinil can decrease AR activity and inhibit polyol pathway. Both in vitro and animal model studies reported the efficacy of sorbinil in controlling the progression of diabetes. Moreover, Sorbinil has been found to be comparatively safer than other ARIs for human use. But, it is still in earlyphase testing for the treatment of diabetic complications clinically.

Conclusion: Sorbinil is an effective ARI, which could play therapeutic role in treating diabetes and diabetic complications. However, advanced clinical trials are required for sorbinil so that it could be applied with the lowest efficacious dose in humans.]]> <![CDATA[Polyphyllin I Induces Cell Cycle Arrest and Cell Apoptosis in Human Retinoblastoma Y-79 Cells through Targeting p53]]>https://www.eurekaselect.comarticle/87750

Method: In the present study, we evaluated the cytotoxic effect of PPI on human retinoblastoma Y-79 cells as well as its underlying molecular mechanism. Our results indicated that PPI treatment significantly inhibited cell proliferation, arrested the cell cycle at G2/M phase and induced cell apoptosis of Y79 cells through the mitochondrial- dependent intrinsic pathway. Moreover, p53 is involved in PPI-induced cytotoxicity in human retinoblastoma Y-79 cells. Exposure to 10 μM PPI for 48 h dramatically induced the expression levels of p53, phosphorylated- p53 and acetylated-p53. Furthermore, blockade of p53 expression effectively attenuated PPI-induced cell cycle arrest and cell apoptosis in Y-79 cells.

Result: These results demonstrated that PPI exhibits anti-proliferation effect on human retinoblastoma Y-79 cells through modulating p53 expression, stabilization and activation. This information shed light on the potential application of PPI in retinoblastoma therapy.]]> <![CDATA[“Micromanaging” Glioblastoma Multiforme: The Potential of MicroRNAs, Circular RNAs, and the Hippo Pathway as Novel Treatment Strategies]]>https://www.eurekaselect.comarticle/91634 <![CDATA[A Synopsis on the Role of Human Papilloma Virus Infection in Cervical Cancer]]>https://www.eurekaselect.comarticle/88898

Objective: In this review, a brief update on cancer, its causes and different types has been discussed along with updated statistics of patient's mortality. A brief overview of cervical cancer and its pathophysiology has been discussed with special emphasis on its causative agent, human papilloma virus (HPV). A brief introduction and update on genetics, molecular pathogenesis and prevalence of HPV and its role in cervical cancer have been added.

Conclusion: This review delivered an updated status of cervical cancer and provide novel therapeutic approaches for targeting HPV. The detailed molecular and genomic information of the HPV help the researchers to develop more effective and efficacious therapeutic strategies and preventive vaccines that will significantly contribute to the control and anticipation of cervical cancer. Ultimately this may open new vistas to get rid of this deadly disease and may offer significant reduction in the numbers of advanced cervical cancers and deaths from cervical cancer in the affected nations.]]> <![CDATA[An Update on MDMX and Dual MDM2/X Inhibitors]]>https://www.eurekaselect.comarticle/90867 <![CDATA[Molecular Interaction and Computational Analytical Studies of Pinocembrin for its Antiangiogenic Potential Targeting VEGFR-2: A Persuader of Metastasis]]>https://www.eurekaselect.comarticle/89741

Objective: The study focuses on virtual screening of compounds from plants of Asteraceae family that bears antiangiogenic potential and thus, inhibiting VEGFR-2 using a computational approach.

Materials and Methods: Structures of phytochemicals were prepared using ChemDraw Ultra 10 software and converted into its 3D PDB structure and minimized using Discovery Studio client 2.5. The target protein, VEGFR-2 was retrieved from RCSB PDB. Lipinski’s rule and ADMET toxicity profiling were carried out on the phytochemicals of the Asteraceae family and the filtered compounds were further promoted for molecular docking and MD simulation analysis. The study extends towards the SOM analysis of Pinocembrin to predict the possible toxic and non-toxic in vivo metabolites via in silico tools (Xenosite Web and PASS online server).

Results: The docking results revealed promising inhibitory potential of Pinocembrin against VEGFR-2 with binding energy of -8.50 kcal/mole as compared to its known inhibitors Sorafenib and YLT192 having binding energy of -6.49 kcal/mole and -8.02 kcal/mol respectively. Further, molecular dynamics (MD) simulations for 10ns were conducted for optimization, flexibility prediction, and determination of folded VEGFR-2 stability. The Hsp90-Pinocembrin complex was found to be quite stable with RMSD value of 0.2nm. Pinocembrin was found to be metabolically stable undergoing phase I metabolism with non-toxic metabolites compared to the standard drug Sorafenib and YLT192.

Conclusion: Obtained results propose Pinocembrin as a multi-targeted novel lead compound that bears outstanding antiangiogenic potential against VEGFR-2.]]> <![CDATA[SCAP/SREBPs are Central Players in Lipid Metabolism and Novel Metabolic Targets in Cancer Therapy]]>https://www.eurekaselect.comarticle/90623 <![CDATA[Drusen in the Peripheral Retina of the Alzheimer’s Eye]]>https://www.eurekaselect.comarticle/88136

Objective: This study compares macular and peripheral drusen load in control and AD eyes.

Methods: Postmortem eye tissues were obtained from donors with a neuropathological diagnosis of AD. Retina from normal donors were processed and categorized into younger (<55 years) and older (>55 years) groups. After fixation and dissection, 3-6 mm punches of RPE/choroid were taken in macular and peripheral (temporal, superior, and inferior) retinal regions. Oil red O positive drusen were counted and grouped into two size categories: small (<63 μm) and intermediate (63-125 μm).

Results: There was a significant increase in the total number of macular and peripheral hard drusen in older, compared to younger, normal eyes (p<0.05). Intermediate hard drusen were more commonly found in the temporal region of AD eyes compared to older normal eyes, even after controlling for age (p<0.05). Among the brain and eye tissues from AD donors, there was a significant relationship between cerebral amyloid angiopathy (CAA) severity and number of temporal intermediate hard drusen (r=0.78, p<0.05).

Conclusion: Imaging temporal drusen in the eye may have benefit for diagnosing and monitoring progression of AD. Our results on CAA severity and temporal intermediate drusen in the AD eye are novel. Future studies are needed to further understand the interactions among CAA and drusen formation.]]> <![CDATA[Hepatitis C Virus Mediated Metastasis in Hepatocellular Carcinoma as a Therapeutic Target for Cancer Management]]>https://www.eurekaselect.comarticle/88242

Methods: We reviewed reports linking expression of HCV encoded proteins with changes in cellular functions. We also compared reports on HCV-induced HCC with those on non-viral and Hepatitis B Virus (HBV) induced HCC. Novel therapeutic approaches for handling metastatic HCC were also reviewed.

Results: HCV infection is associated with expression of multiple pro-metastatic factors in HCC patients. HCV encoded proteins can directly induce pro-metastasis cellular functions. HCV-induced HCC has a greater chance of recurrence than any non-viral and Hepatitis B Virus (HBV) induced HCC. Recent advances in understanding of evolutionary dynamics of tumor argue that trying to prevent spreading of cancer may ultimately prove to be a better approach than striving to cure it. Inhibiting the metastasis can thereby substantially increase the survival period in patients. Host cell protein Nm23-H1 is a known suppressor of tumor metastasis and has been shown to be modulated by proteins encoded by different viruses associated with cancers.

Conclusion: Nm23-H1 is an important therapeutic target for virus mediated malignancies. This review is an attempt to summarize the current state of understanding of cancer cell metastasis in HCV induced tumors, and argues for approaches based on targeting host and viral factors critical for cancer metastasis as therapeutic targets.]]> <![CDATA[Involvement of CD24 in Multiple Cancer Related Pathways Makes It an Interesting New Target for Cancer Therapy]]>https://www.eurekaselect.comarticle/85356 <![CDATA[Zoledronic Acid: Pleiotropic Anti-Tumor Mechanism and Therapeutic Outlook for Osteosarcoma]]>https://www.eurekaselect.comarticle/68072

Objective: The present review summarizes the controversial effects of zoledronic acid on primary tumor burden and pulmonary metastases in osteosarcoma. We also analyze the clinical effectiveness of zoledronic acid alone and in combination with chemotherapeutic drugs for the treatment of osteosarcoma.

Conclusion: Zoledronic acid exhibits diverse anti-tumor effects in osteosarcoma in vitro, however, the in vivo effect is still controversial. Further preclinical and clinical studies are needed to clarify the effects of zoledronic acid in osteosarcoma.]]> <![CDATA[4-aryl/heteroaryl-4H-fused Pyrans as Anti-proliferative Agents: Design, Synthesis and Biological Evaluation]]>https://www.eurekaselect.comarticle/85842

Description: Significant inhibition was exhibited by the compounds against HCT-116 (Colon) and PC-3 (Prostate) cell lines while A-549 (Lung) cell lines, MiaPaCa-2 (Pancreatic) cell lines and HL-60 (Leukemia Cancer) cell lines were almost resistant to the exposure of the test compounds. Compound FP-(v)n displayed noteworthy cytotoxicity towards HCT-116 malignant cells with the IC50 value of 0.67 µM. It induces apoptosis as revealed by several biological endpoints like apoptotic body formation, through DAPI staining, phase contrast microscopy and mitochondrial membrane potential loss. Moreover FP-(v)n is a potent apoptotic inducer confirmed by cell cycle arrest and ROS generation. The cell phase distribution studies indicate an augment from 4.94 % (control sample) to 39.68 % (sample treated with 1.5 µM compound FP-(v)n) in the apoptotic population. Compound FP-(v)n inhibits the tumor growth in Ehrlich ascites carcinoma (EAC), Ehrlich Tumor (ET, solid) and sarcoma-180 (solid) mice models. Additionally, it was established to be non-toxic at maximum tolerated dose of 1000 mg/kg in acute oral toxicity in Swiss-albino mice.

Conclusion: The current study provides an insight into anti-cancer potential of FP-(v)n, which might be valuable in the treatment of tumor.]]> <![CDATA[Tumor-Targeting Peptides: Ligands for Molecular Imaging and Therapy]]>https://www.eurekaselect.comarticle/82910 <![CDATA[Meet Our Editorial Board Member]]>https://www.eurekaselect.comarticle/89099 <![CDATA[The Complexity of DEK Signaling in Cancer Progression]]>https://www.eurekaselect.comarticle/83599 <![CDATA[Quinoxalinone as a Privileged Platform in Drug Development]]>https://www.eurekaselect.comarticle/86631 <![CDATA[Aptamer-Mediated Polymeric Vehicles for Enhanced Cell-Targeted Drug Delivery]]>https://www.eurekaselect.comarticle/76638

Objective: The application of molecularly engineered biodegradable and biocompatible polymeric particles with tunable features such as surface area and chemistry, particulate size distribution and toxicity creates opportunities to develop smart aptamer-mediated delivery systems for controlled drug release.

Results: This article discusses opportunities for particulate aptamer-drug formulations to advance current drug delivery modalities by navigating active ingredients through cellular and biomolecular traffic to target sites for sustained and controlled release at effective therapeutic dosages while minimizing systemic cytotoxic effects.

Conclusion: A proposal for a novel drug-polymer-aptamer-polymer (DPAP) design of aptamer-drug formulation with stage-wise delivery mechanism is presented to illustrate the potential efficacy of aptamer- polymer cargos for enhanced cell targeting and drug delivery.]]> <![CDATA[Emerging Roles of Meis1 in Cardiac Regeneration, Stem Cells and Cancer]]>https://www.eurekaselect.comarticle/84960

Objective: We have recently demonstrated that knocking out of Meis1 in adult cardiomyocytes resulted in the induction of cardiomyocyte proliferation. This suggests that targeting of Meis1 might be utilized in the manipulation of cardiomyocyte cell cycle post cardiac injuries. In addition, hematopoietic stem cell (HSC) specific deletion of Meis1 leads to in vivo expansion of HSCs pool. Thus, targeting Meis1 may lead to not only cell cycle entry but also ex vivo and in vivo expansion of HSCs. On the other hand, Meis1 transcriptionally regulates the expression of hypoxic tumor markers, namely Hif-1α and Hif-2α. Hif-1α and Hif-2α are involved in the induction of cytoplasmic glycolysis and scavenging of reactive oxygen species (ROS), respectively.

Conclusion: Studies highlight emerging roles of Meis1 towards development of new therapeutic approaches in the treatment of myocardial injuries, bone failure, and cancer.]]> <![CDATA[Oncolytic Virotherapy and Gene Therapy Strategies for Hepatobiliary Cancers]]>https://www.eurekaselect.comarticle/82572 <![CDATA[Nutlin-3, A p53-Mdm2 Antagonist for Nasopharyngeal Carcinoma Treatment]]>https://www.eurekaselect.comarticle/84809 <![CDATA[CDK5 and MAPT Gene Expression in Alzheimer's Disease Brain Samples]]>https://www.eurekaselect.comarticle/84766

Objective: This study aimed to characterize the expression of the MAPT gene and CDK5 (the gene involved in cell cycle regulation) in brain samples from patients with AD and controls.

Method: The real-time-PCR technique was used to characterize 150 samples from three areas of the brain (entorhinal cortex, auditory cortex, and hippocampus) of 26 AD patients and 24 healthy elderly subjects.

Results: When the brain samples were analyzed collectively, a decrease in CDK5 and MAPT gene expression was found in AD patients. When each groups' samples were separated by area of the brain and compared, significant differences were found in CDK5 expression in the hippocampus and the entorhinal cortex. In both cases, mRNA was lower in the AD group (p=0.0001); however, the same analysis using the MAPT gene revealed no significant statistical differences. No statistical differences were found when gene expression was compared between the different regions of the brain within each group.

Conclusion: These results may contribute to a better understanding of the involvement of CDK5 and MAPT genes in AD in that they consider different areas of the brain that are affected differently based on disease progression. The main challenge is to establish an effective therapy for this debilitating disease in the future.]]> <![CDATA[Therapeutic Application of Natural Medicine Monomers in Cancer Treatment]]>https://www.eurekaselect.comarticle/84772

Methods: After extensively reviewing papers related to NMM studies in cancers, we grouped NMMs into six categories based on their chemical structures. We summarized the anti-cancer activities of these NMMs and current knowledge of molecular mechanisms for them to exert their functions.

Results and Conclusion: Many NMMs from plants can effectively inhibit cancer cells with low or tolerable toxicity to patients. Some NMMs have been well-characterized for their anti-cancer activities and have already been used as clinical drugs or adjuvant agents; however, the mechanisms underlying the cancer suppressive activities of most NMMs remain poorly understood. Many NMMs can be used as initial structural scaffolds to design and develop novel therapeutics against cancers. This review summarizes reports related to signaling pathways mediated by different NMMs and can provide a theoretical basis for clinical application and new drug development of NMMs.]]> <![CDATA[Therapeutic Peptide Mimetics Looking for a Turn to Block Aberrant Players of Malignancy]]>https://www.eurekaselect.comarticle/84128

Methods: In the last decade, attempts have been reported to test several new class of anticancer drug such as miRNA mimetics, RNA enzymes, small molecular inhibitors, DNA repair protein inhibitors and peptide mimetics.

Results: With the advent of rapidly growing genomic, epigenomic and proteomic data, design and application of peptide mimetics appear to thrive and sustain for an impactful cancer therapy. However, certain bottlenecks are envitable such as delivery of peptide mimetics drug in clinical settings, reducing the side effects, immune responses and pharmacokinetic properties.

Conclusion: This review discusses emerging issues and potential avenues related to the scope and limitations of peptide mimetics in cancer treatment.]]> <![CDATA[Neurokinin-1 Receptor Antagonists in Lung Cancer Therapy]]>https://www.eurekaselect.comarticle/82493

Conclusion: In this review, we update and discuss the data regarding the possible use of NK-1R antagonists in the treatment of lung cancer.]]> <![CDATA[Modulators of Acetylcholinesterase Activity: From Alzheimer's Disease to Anti-Cancer Drugs]]>https://www.eurekaselect.comarticle/84521

Objective: This contribution will discuss a broad range of possible application of different AChE inhibitors as drugs, from well-known anti-Alzheimer's disease drugs to their use in cancer treatment in future. Emphasis will be put on various known AChE inhibitors classes, whose application as drugs could be controversy, as well as on newly investigated natural products, which can also modulate AChE activity.

Conclusion: It is not clear a patient treated for neurodegenerative condition prone to increased risk for some types of cancer and vice versa. This is necessary to keep in mind during rational drug design process for all therapies, which are based on AChE as a target molecule.]]> <![CDATA[Letter to the Editor: The Versatility of Tumor Suppressor Proteins and its Therapeutic Potential]]>https://www.eurekaselect.comarticle/85568 <![CDATA[Synthesis and Preliminary Cytotoxicity Studies of 1-[1-(4,5-Dihydrooxazol- 2-yl)-1H-indazol-3-yl]-3-phenylurea and 3-phenylthiourea Derivatives]]>https://www.eurekaselect.comarticle/82136

Objective: The aim of this work was to obtain a new class of N-substituted 3-amino-1H-indazole derivatives with cytotoxic activity towards cancer cells.

Method: Two series of 1-[1-(4,5-dihydrooxazol-2-yl)-1H-indazol-3-yl]-3-phenylurea and 3- phenylthiourea derivatives 7-17 and 18-22, respectively, were prepared and screened for their potential in vitro cytotoxic activities against lung carcinoma LCLC-103H cell line using a crystal violet microtiter plate assay.

Results: All the urea derivatives, except the compound 8, were inactive at a concentration of 20 μM attainable in cancer cells, while the thiourea derivatives showed a pronounced cancer cell growth inhibitory effects. The most potent 1-[1-(4,5-dihydrooxazol-2-yl)-1H-indazol-3-yl]-3-ptolylthiourea (19) exhibited cytotoxicity on the lung cancer LCLC-103H and cervical cancer SISO cell lines at a concentration of 10 µM. Moreover, compound 19 displayed cytostatic activity against pancreas cancer DAN-G cell line.

Conclusion: The 1-[1-(4,5-dihydrooxazol-2-yl)-1H-indazol-3-yl]-3-phenylthiourea derivatives described herein may serve as a useful scaffold for the search for novel anticancer agents.]]> <![CDATA[Cell Cycle Arrest as a Therapeutic Target of Acute Kidney Injury]]>https://www.eurekaselect.comarticle/78368 <![CDATA[Synthetic Methods of Quinoline Derivatives as Potent Anticancer Agents]]>https://www.eurekaselect.comarticle/83382

Method: Some molecules are synthesized using quinolones as precursor reactant, which is another effective product of quinoline, also showing significant activity against malignant tumors. The presence of nitrogen in it and its ability to bind with enzymes like gyrase, topoisomerase II and kinase have also proven it with antitumor activity.

Conclusion: This review encapsulates the recent advances in the synthesis and anticancer activity of Quinoline derivatives.]]> <![CDATA[Pathological and Therapeutic Aspects of Long Noncoding RNAs in Osteosarcoma]]>https://www.eurekaselect.comarticle/81723

Objective: This review study focused on the role of long non coding RNAs (lncRNAs) in OS progression, and presented update reports on OS treatment by targeting specific lncRNAs.

Method: We have acquired information on OS and lncRNAs from scientific databases like google scholar, pubmed and scopus, and reviewed for this study.

Results: The lncRNAs regulate a number of biological processes, and abnormal expression of lncRNAs could play role in many cancers and other human diseases. Interestingly, some lncRNAs can act as oncogenes, while some act as tumor suppressor genes. A number of studies revealed that targeting the specific lncRNAs by RNA interferance technology may provide a novel therapeutic strategy in the treatment of OS.

Conclusion: LncRNAs could be a promising biomarker and might be a potential therapeutic target in OS patients.]]> <![CDATA[The Basic Mechanism of Hair Growth Stimulation by Adipose-derived Stem Cells and Their Secretory Factors]]>https://www.eurekaselect.comarticle/85533

Objective: This review focuses on the effect of ADSCs and their secretory factors on the stimulation of hair growth in vitro, ex vivo and in vivo.

Results: The conditioned media of ADSCs (ADSC-CM) increases the proliferation rate of human follicular cells. ADSCs-derived proteins improve hair growth and protect human dermal papilla cells against cytotoxic injury caused by androgen and reactive oxygen species. Moreover, ADSC-CM induces the anagen phase and promotes hair growth in mice, and enhances the elongation of hair shafts in ex vivo human hair organ cultures.

Conclusion: ADSC-CM promotes hair growth in vitro, ex vivo, and in vivo. Given that ADSCs are one of the most accessible sources of MSCs, ADSC-derived proteins may be feasible clinical therapeutic agents for the treatment of hair loss.]]> <![CDATA[Retinoic Acid Signaling in P19 Stem Cell Differentiation]]>https://www.eurekaselect.comarticle/76565 <![CDATA[Pharmacological Inhibitors of NAD Biosynthesis as Potential An ticancer Agents]]>https://www.eurekaselect.comarticle/84232

Objective and Method: The main objective of this article is to review the recent patents which develop and implicate the chemical inhibitors of the key NAD+ biosynthetic enzymes for cancer treatment. We first discuss the biological principles of NAD+ metabolism in normal and malignant cells, with a focus on the feasibility of selectively targeting cancer cells by pharmacological inhibition of nicotinamide phosphoribosyltransferase (NAMPT) and indoleamine/tryptophan 2,3-dioxygenases (IDO/TDO), the rate-limiting salvage and de novo NAD+ biosynthetic enzymes, respectively. We then analyze a series of recent patents on development and optimization of chemical scaffolds for inhibiting NAMPT or IDO/TDO enzymes as potential anticancer drugs.

Conclusion and Results: We have reviewed 16 relevant patents published since 2015, and summarized the chemical properties, mechanisms of action and proposed applications of the patented compounds. Without a better understanding of the properties of these compounds, their utility for further optimization and clinical use is unknown. For the compounds that have been tested using cell and mouse models of cancer, results look promising and clinical trials are currently ongoing to see if these results translate to improved cancer treatments.]]>
<![CDATA[Epithelial Mesenchymal Transition in Cancer Progression: Prev entive Phytochemicals]]>https://www.eurekaselect.comarticle/82985

Objective: The present review aims to provide a detailed description of the nature and characteristics of EMT in physiological and pathophysiological conditions and the scope of phytochemicals in its prevention.

Method: Details regarding the initiation, progression as well as prevention of pathologic EMT and metastasis and recent patents on preventive phytochemicals were obtained from PubMed literatures and patent databases.

Results: The phenotypic changes during EMT are regulated by transcription factors like Snail, Slug, Twist and Zeb, which are activated through diverse signaling pathways of TGF-β, NF-&kgr;B, Wnt and Notch. Scientific documentations till date have identified numerous phytocompounds that are potent enough to interfere with these signaling pathways, which in turn prevent pathological implications of EMT. Present review also discusses 28 recent patents on those phytocompounds.

Conclusion: EMT is a significant pharmacological target for developing preventive agents to combat pathological conditions like malignancy. Many of the phytochemicals cited in this review are being enrolled for different phases of clinical trials for their efficacy. In spite of the major limitations regarding bioavailability, sensitivity and tolerance of these compounds, their synthetic analogs, formulations and efficient drug delivery systems are also being attempted which will hopefully generate productive and promising results in near future.]]>
<![CDATA[Metabolomics Applications in Precision Medicine: An Oncological Perspective]]>https://www.eurekaselect.comarticle/84586 <![CDATA[Small Molecule Drugs and Targeted Therapy for Melanoma: Current Strategies and Future Directions]]>https://www.eurekaselect.comarticle/82841 <![CDATA[Identification and Characterization of a Chemical Compound that Inhibits Methionyl-tRNA Synthetase from <i>Pseudomonas aeruginosa</i>]]>https://www.eurekaselect.comarticle/82566Pseudomonas aeruginosa is an opportunistic pathogen problematic in causing nosocomial infections and is highly susceptible to development of resistance to multiple antibiotics. The gene encoding methionyl-tRNA synthetase (MetRS) from P. aeruginosa was cloned and the resulting protein characterized.

Methods: MetRS was kinetically evaluated and the KM for its three substrates, methionine, ATP and tRNAMet were determined to be 35, 515, and 29 μM, respectively. P. aeruginosaMetRS was used to screen two chemical compound libraries containing 1690 individual compounds.

Results: A natural product compound (BM01C11) was identified that inhibited the aminoacylation function. The compound inhibited P. aeruginosa MetRS with an IC50 of 70 μM. The minimum inhibitory concentration (MIC) of BM01C11 was determined against nine clinically relevant bacterial strains, including efflux pump mutants and hypersensitive strains of P. aeruginosa and E. coli. The MIC against the hypersensitive strain of P. aeruginosa was 16 μg/ml. However, the compound was not effective against the wild-type and efflux pump mutant strains, indicating that efflux may not be responsible for the lack of activity against the wild-type strains. When tested in human cell cultures, the cytotoxicity concentration (CC50) was observed to be 30 μg/ml. The compound did not compete with methionine or ATP for binding MetRS, indicating that the mechanism of action of the compound likely occurs outside the active site of aminoacylation.

Conclusion: An inhibitor of P. aeruginosa MetRS, BM01C11, was identified as a flavonoid compound named isopomiferin. Isopomiferin inhibited the enzymatic activity of MetRS and displayed broad spectrum antibacterial activity. These studies indicate that isopomiferin may be amenable to development as a therapeutic for bacterial infections.]]>
<![CDATA[HR+, HER2– Advanced Breast Cancer and CDK4/6 Inhibitors: Mode of Action, Clinical Activity, and Safety Profiles]]>https://www.eurekaselect.comarticle/82571

Objectives: 1. Discuss the mode of action of the three CDK4/6 inhibitors in late clinical development: palbociclib (PD-0332991; Pfizer), ribociclib (LEE011; Novartis), and abemaciclib (LY2835219; Lilly). 2. Describe the efficacy and safety data relating to their use in HR+, HER2– advanced breast cancer. 3. Discuss the key side effects associated with CDK4/6 inhibitors along with considerations for adverse event management and patient monitoring.

Method: Relevant information and data were assimilated from manuscripts, congress publications, and online sources.

Results: CDK4/6 inhibitors have demonstrated improved progression-free survival in combination with endocrine therapy compared with endocrine therapy alone. The side-effect profile of each agent is described, along with implications for patient monitoring, and considerations for patient care providers and pharmacists.

Conclusion: Addition of a CDK4/6 inhibitor to endocrine therapy increases efficacy and delays disease progression. Insight into the unique side-effect profiles of this class of agents and effective patient monitoring will facilitate the successful use of CDK4/6 inhibitor-based therapies in the clinic.]]>
<![CDATA[From Leflunomide to Teriflunomide: Drug Development and Immunosuppressive Oral Drugs in the Treatment of Multiple Sclerosis]]>https://www.eurekaselect.comarticle/80240

Methods: Review of online content related to oral immunosuppressants in MS with an emphasis on Teriflunomide.

Results: Teriflunomide and Cladribine are second-generation immunosuppressants that are efficient in the treatment of MS patients. For Teriflunomide, a daily dose of 14 mg reduces the annualized relapse rate (ARR) by more than 30% and disability progression by 30% compared to placebo. Cladribine reduces the ARR by about 50% compared to placebo but has not yet been licensed due to unresolved safety concerns. We also discuss the significance of older immunosuppressive compounds including Azathioprine, Mycophenolate mofetile, and Cyclophosphamide in current MS therapy.

Conclusion: Teriflunomide has shown a favorable safety and efficacy profile in RRMS and is a therapeutic option for a distinct group of adult patients with RRMS.]]>
<![CDATA[An Investigative Approach to Treatment Modalities for Squamous Cell Carcinoma of Skin]]>https://www.eurekaselect.comarticle/78216

Methods: Research evidence shows that nanoparticle based therapeutic delivery to squamous cell carcinoma is equanimous to lead therapeutic approaches for intervention of cancer growth. Active chemotherapeutic approach is one of the leading therapies to such cancer cells due specific selectivity towards the EGFR-receptors over-expressed in tumor cells. Review of numerous research publications revealed innate toxicity of chemotherapeutic agents, and substantiated active receptor mediated drug targeting for therapeutic regime. These actively functionalized nanoparticles have been delivered to the targeted cells with higher selectivity, minimal toxicity and better retention in the cell.

Results: Numerous approaches and strategies have been designed till date for successful delivery of drug to cancer cells. The techniques have shown tremendous improvement in getting normalcy of carcinomas but a few have been marketed so far.

Conclusion: Indeed, receptor based drug targeting approach through molecular signal transduction pathways involved in skin cancer development will provide insight into squamous carcinoma. Despite of these, other such challenges in drug delivery to squamous cell carcinoma need further clarification.]]>
<![CDATA[Glioblastoma Targeted Gene Therapy Based on pEGFP/p53-Loaded Superparamagnetic Iron Oxide Nanoparticles]]>https://www.eurekaselect.comarticle/83885

Material and Method: After magnetic and non-magnetic nanoparticles were internalized by KB cells, their location in these cells was examined by transmission electron microscopy. Transfection efficiency of DNA to U87 cells was evaluated by fluorescence microscopy, real time PCR, flowcytometry, and Western immuno-blotting. When a magnetic field was applied, a large number of magnetic nanoparticles accumulated in KB cells, appearing as black dots scattered in the cytoplasm of cells. Fluorescence microscope examination showed that transfection of the DNA to U87 target cells was highest in cells treated with magnetic nanoparticles and exposed to a magnetic field. Also it was reflected in significantly increased mRNA level while the p53 protein level was decreased.

Conclusion: It could be concluded that a significant increase in total apoptosis was induced in cells by magnetic nanoparticles, coupled with exposure to a magnetic force (p ≤0.01) as compared with cells that were not exposed to magnetism.

]]>
<![CDATA[Topoisomerase II Inhibitors and Poisons, and the Influence of Cell Cycle Checkpoints]]>https://www.eurekaselect.comarticle/80145 <![CDATA[Epstein-Barr Virus-associated Gastric Cancer and Potential Mechanisms of Oncogenesis]]>https://www.eurekaselect.comarticle/78574

Conclusion: Here, we discuss the principal and distinctive carcinogenic routes promoted by EBV in the gastric epithelium.

]]>
<![CDATA[Molecular Approaches Target to Immunotherapy for HPV-Associated Cancers]]>https://www.eurekaselect.comarticle/80388

Method: In this short review, we discuss development of immunotherapy for HPV-associated cancers and recent progresses in our understanding of the immunopathology of HPV infection.

Results: Recent research advances have shown that molecular approaches target to immunotherapy for HPV infection-induced cancers to have the great potential and promise for developing immunotherapeutic vaccines. So far, the vast majority of the immunotherapeutic vaccines that are being tested are designed to target HPV viral genes and their proteins especially two E6 and E7 oncogenes.

Conclusion: The developing immunotherapeutic vaccines aim to boost cell-mediated immunity. The boosted cell-mediated immunity strengthens the body’s natural defenses to fight active infection and disease, thus to treat the existing cancers.

]]>
<![CDATA[Targeting the Akt/PI3K Signaling Pathway as a Potential Therapeutic Strategy for the Treatment of Pancreatic Cancer]]>https://www.eurekaselect.comarticle/81542 <![CDATA[Sphingolipids in Genetic and Acquired Forms of Chronic Kidney Diseases]]>https://www.eurekaselect.comarticle/81006 <![CDATA[MRP1-dependent Collateral Sensitivity of Multidrug-resistant Cancer Cells: Identifying Selective Modulators Inducing Cellular Glutathione Depletion]]>https://www.eurekaselect.comarticle/79806 <![CDATA[The Polyhedric Abl Kinases and their Pharmacologic Inhibitors]]>https://www.eurekaselect.comarticle/79640 <![CDATA[C. elegans as Model for Drug Discovery]]>https://www.eurekaselect.comarticle/81393 <![CDATA[Targeted Theranostics Against Solid Cancer Using Metal Bond Milk Protein and Aptamers]]>https://www.eurekaselect.comarticle/81359 <![CDATA[Preclinical and Clinical Studies of Chidamide (CS055/HBI-8000), An Orally Available Subtype-selective HDAC Inhibitor for Cancer Therapy]]>https://www.eurekaselect.comarticle/78144 <![CDATA[Marine Derived Anticancer Drugs Targeting Microtubule]]>https://www.eurekaselect.comarticle/80902

Objective: The emphasis of the article is to provide an overview of some of the most promising marine derived MTAs and highlight their major characteristics in brief.

Method: Patent databases such as USPTO, Espacenet and WIPO were searched systematically for recent patents published from 2006 up to 2016. Numerous data retrieved was analyzed critically, and only those patents focusing on the chemical synthesis and/or modifications of marine derived MTAs along with a significant demonstration of their in vitro and/or in vivo activity are summarized here.

Results: Some of the marine derived MTAs have significant antiproliferative potency against a wide array of cancers and are also able to overcome multidrug resistance.

Conclusion: The marine derived MTAs hold great potential in the field of cancer therapeutics and are gradually advancing in the clinical set up. A deeper understanding of the molecular mechanisms combined with innovative therapeutic regimen would lead to major advances in the field.]]> <![CDATA[Targeting Nanomedicine to Brain Tumors: Latest Progress and Achievements]]>https://www.eurekaselect.comarticle/80614 <![CDATA[Recent Advances in Application of Poly-Epsilon-Caprolactone and its Derivative Copolymers for Controlled Release of Anti-Tumor Drugs]]>https://www.eurekaselect.comarticle/80912

Methods: This mini-review focused on the recent progress in application of poly-epsiloncaprolactone based materials for controlled release of cancer therapy drugs. A careful search was performed on web of science, mainly focused on the related papers published from 2013 to 2016.

Conclusion: Recent advances in applying poly-epsilon-caprolactone for controlled delivery and targeting release of chemical anti-tumor drugs were summarized in this mini-review. Benefited from the efforts of scientists all over the world, various chemotherapeutic drug delivery systems based on different formulations of poly-epsilon-caprolactone related materials have been evaluated. It has been widely recognized that the introduction of of poly-epsilon-caprolactone components into drug delivery systems would increase drug loading capacity, decrease leakage, prolong releasing period and result in controllable releasing rate. Especially with the development of environment-responsive delivery systems (pH-, thermo-, magnetic field- and light-responsive drug carriers), enhanced tumor cell targeting potential, as well as decreased systemic toxicity would be realized.

]]>
<![CDATA[Cathepsin D as a Promising Target for the Discovery of Novel Anticancer Agents]]>https://www.eurekaselect.comarticle/80661

Implication as a Target: Studies have confirmed the role and significance of CATD in an assortment of pathological conditions like Atherosclerosis, Alzheimer, Cancer, Cardiovascular, Huntington and Parkinson diseases. Amalgamated and veiled as inactive proCATD, it undergoes diverse cleavages to attain a desired conformation in an acidic milieu to act as a functionally active protein. In search of new candidate target (s) for cancer, CATD has attracted a wide group of investigators across the globe and is being recognized as a well-defined marker in cancer especially for breast and hormone-dependent cancer.

Methods: In this review, PubMed, Sci-finder and other search engines were used to gather information on Cathepsin D. The necessary and relevant information was thoroughly studied to make the article appropriate to highlight all the aspects related to Cathepsin D and its role in cancer.

Findings & Conclusion: The present review illustrates structural, functional and regulatory aspects of CATD in cancer, its significant role in angiogenesis, metastasis, invasion, apoptosis, cell proliferation, and therapeutic potential besides the benefits of targeting CATD by the natural products in cancer chemoprevention.

]]>
<![CDATA[When Neighbors Talk: Colon Cancer Cell Invasion and Tumor Microenvironment Myofibroblasts]]>https://www.eurekaselect.comarticle/79354 <![CDATA[Development of Selective Cyclin-Dependent Kinase 4 Inhibitors for Antineoplastic Therapies]]>https://www.eurekaselect.comarticle/80769 <![CDATA[9-bis[2-(pyrrolidin-1-yl)ethoxy]-6-{4-[2-(pyrrolidin-1-yl)ethoxy]phenyl}-11H-indeno[1, 2-c]quinolin-11-one (BPIQ), A Quinoline Derivative Inhibits Human Hepatocellular Carcinoma Cells by Inducing ER Stress and Apoptosis]]>https://www.eurekaselect.comarticle/77496

Objective: We further investigated the anti-HCC effects of BPIQ, including apoptosis and the modulation of ER stress.

Methods: Both trypan blue exclusion assay and colony formation assay were performed to examine whether BPIQ affects the growth of HCC cell lines Ha22T and Huh7. Flow cytometry-based assay was performed for determining the cell cycle distribution and apoptosis. Western blot assay was conducted for detecting the changes in apoptosis- and endoplasmic reticulum (ER) stress-associated proteins.

Results: BPIQ inhibits cell growth and induces the apoptosis of both Ha22T and Huh7 cell lines significantly. The level of γH2AX, an endogenous DNA damage biomarker was dramatically increased suggesting the involvement of DNA damage pathway in BPIQ-induced apoptosis. Further, BPIQ down-regulates the pro-survival proteins, survivin, XIAP and cyclin D1. BPIQ also may regulate ER stress response through modulating the levels of ER stress-related proteins Glucose-regulated protein of 78 kD (GRP78), Inositol-requiring kinase-1α (IREα), C/EBP homologous protein (Chop) and calnexin.

Conclusions: The anti-HCC effect of BPIQ may occur through down-regulating pro-survival proteins, and the modulation of ER stress may contribute to the BPIQ-induced apoptosis of HCC cells. The chemotherapeutic or chemopreventive applications of BPIQ for HCC treatment will be worthy of further investigation in future.

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<![CDATA[Ultrasound Therapeutics– A Review]]>https://www.eurekaselect.comarticle/77815 <![CDATA[Five Pediatric Cancers – Update on Genetic Implications]]>https://www.eurekaselect.comarticle/80292 <![CDATA[Metastatic Cell Dormancy and Re-activation: An Overview on Series of Molecular Events Critical for Cancer Relapse]]>https://www.eurekaselect.comarticle/78143 <![CDATA[Template Synthesis of Tubular Nanostructures for Loading Biologically Active Molecules]]>https://www.eurekaselect.comarticle/80526 <![CDATA[rDNA Mediated Bioconjugates: Fusion Proteins and their Intended Use in Medicine]]>https://www.eurekaselect.comarticle/80527 <![CDATA[Gliomas: New Perspectives in Diagnosis, Treatment and Prognosis]]>https://www.eurekaselect.comarticle/80778 <![CDATA[Interconnection of Estrogen/Testosterone Metabolism and Mevalonate Pathway in Breast and Prostate Cancers]]>https://www.eurekaselect.comarticle/73031 <![CDATA[A Perspective on Stem Cells as Biological Systems that Produce Differentiated Osteoblasts and Odontoblasts]]>https://www.eurekaselect.comarticle/79286 <![CDATA[The Role of the Transcription Factor E2F1 in Hepatocellular Carcinoma]]>https://www.eurekaselect.comarticle/76004