Anticancer Research Articles

Computational and In vitro Elucidation of Indolenine-barbituric Acid Zwitterions as Potential Chemotherapeutical Agents

Introduction: The continuous pursuit of novel chemotherapeutical agents with improved efficacy and reduced adverse effects remains a critical area of research despite advancements in chemotherapy. We have previously synthesized indolenine and barbituric acid zwitterion scaffolds 1–10 sustainably; however, their precise chemotherapeutical properties are still lacking. Methods: In this present work, we conducted in silico ADMET analyses, molecular docking calculations, DNA binding studies, and cytotoxicity assays on these zwitterions. Results and Discussion: Among the 10 zwitterions, zwitterion 3 bearing a methoxy group demonstrated the highest drug-likeness score, low toxicity, as well as no violation of Lipinski’s rule of five and Veber’s rule. Both molecular docking calculations and DNA binding studies suggested that the minor groove of DNA is the most probable molecular target of 3 among the others (i.e., topoisomerase and tubulin). In addition, zwitterion 3 exhibited selective cytotoxicity against a wide array of human cancer cell lines without noticeable effect against the normal human colon fibroblast CCD- 18Co. Conclusion: Overall, these preliminary findings from our combined computational and experimental strategy suggested that 3 remains promising for further elaboration as a chemotherapeutic agent.

Anti-Tumor Activity of Indole: A Review

: Generally, heterocyclic compounds are included in a large class of pharmacologically active compounds. The indole scaffold in this category is widely distributed in nature and present in many active compounds, especially anti-cancer agents. Due to its unique physicochemical and biological properties, the indole platform has been considered a favorable scaffold in anti-cancer drug design and development. Various indole compounds (synthetic, semisynthetic, and natural) show remarkable anti-proliferative activity. According to the recent literature, this review describes the role of indole scaffolds as anti-cancer agents. Indole was reported to induce anti-tumor activity through multiple mechanisms, for example, Epidermal Growth Factor Receptors (EGFR), histone deacetylase (HDAC), kinase, DNA-topoisomerases, and tubulin inhibition. The current review focuses on some indole compounds with amazing effects against different types of cancers as there are too many FDA-approved drugs, for example, osimertinib, alectinib, and anlotinib in NSCLC treatment, panobinostat in multiple myeloma, midostaurin in acute myeloid leukemia treatment, etc. Moreover, several compounds are still in clinical trials to treat different cancer types. Additionally, there are some oxindole derivatives with potent inhibition against different types of tumors, such as ovarian cancer, colorectal cancer, and prostate cancer. Different series of oxindoles are promising and recommended for further studies due to their remarkable inhibition of tumor cells. Accordingly, the collection of data on a pharmacologically significant motif might aid researchers in further employing indoles in developing novel anti-cancer drugs with potentially fewer side effects and higher potency against this rapidly spreading disease.

The impact of the COVID-19 pandemic on the dispensing of systemic anti-cancer therapy (SACT) in Ireland: a population based study

ObjectivesThe COVID-19 pandemic had considerable implications for cancer related care. This study aimed to examine its impact on the dispensing of systemic anti-cancer therapy (SACT) in Ireland. Study designA repeated cross-sectional design was used which involved a quasi-experimental interrupted time series analysis (ITSA), and autoregressive integrated moving average (ARIMA) models. MethodsThis nationally representative study utilised monthly pharmacy claims (i.e. dispensing) data from community and hospital schemes. Dispensed items among individuals prescribed any SACT from January 2019 to April 2021 were included. ResultsDuring the study period, 641,273 SACT items were dispensed, including 57,199 chemotherapeutic agents (8.9%), 15,970 immunotherapeutic agents (2.5%), 87,813 targeted therapies (13.7%), and 480,291 (74.9%) endocrine therapies. There were on average 3.3 and 4.1 fewer immunotherapy and targeted therapy agents, respectively, dispensed per 100,000 population per month post-March 2020 (vs. expected), compared to the level prior to March 2020. For endocrine therapy, there was a significant slowing of the trend post-March 2020 compared to the pre-pandemic period (slope change = -1.72, 95% CI -2.9 to -0.5; p<0.01). ConclusionThere was a significant level decrease in the dispensing of immunotherapy and targeted therapy during the first year of the pandemic, and a slowing of the trend for endocrine therapies. However, no differences in the dispensing of other SACT were observed.

Harnessing potential COX-2 engagement for boosting anticancer activity of substituted 2-mercapto-4(3H)-quinazolinones with promising EGFR/VEGFR-2 inhibitory activities

We designed and synthesized new quinazolinone-tethered phenyl thiourea/thiadiazole derivatives 4–26. Based on their structural characteristics, these compounds were proposed to have a multi-target mode of action for their anticancer activities. Using the MTT assay method, antiproliferative effects were assessed against three human cancer cell lines (HEPG-2, MCF-7, and HCT-116). In vitro assessment for enzymatic inhibitory activity of the most active compounds 4, 9 and 20 was done for EGFR, VEGFR-2 and COX-2 as potential targets. The screened compounds showed low micromolar IC50 inhibitory effects against the three targets. Compound 9 demonstrated similar EGFR/VEGFR-2 inhibitory effect to the control drugs and potential inhibitory activity for COX-2 enzyme. In MCF-7 cells, the most active analog 9 caused 41.02% total apoptosis, and arrested the cell cycle at the G2/M phase. Taken as a whole, the findings of this study provide significant new understandings into the relationship between COX inhibition and cancer therapy. Furthermore, the outcomes showcased the encouraging efficacy of these compounds with a multi-target mechanism, making them excellent choices for additional research and development into possible anticancer drug.

Insights into the anticancer effects of galangal and galangin: A comprehensive review

BackgroundsCancer continues to be the leading cause of death worldwide, significantly impacting both health and the economy. Natural products have emerged as promising sources for the development of new anticancer drugs, with galangal and their active ingredient, galangin, garnering substantial interest. PurposeThis study summarizes recent findings on the anticancer properties of galangal and galangin, highlighting their potential to target various cancer types. MethodsWe systematically searched the literature across PubMed, Web of Science, and Google Scholar, using keywords such as “Alpinia officinarum,” “Alpinia galanga”, “galangal,” and “galangin.” This thorough approach allowed us to gather and compile a comprehensive collection of existing research on the topic. ResultsThis article provided a thorough analysis of the distribution of galangal, the methods used to extract the active compounds of galangal, and the anticancer properties of both galangin and galangal. It is important to note that galangal and galangin primarily function by regulating the signaling pathways of PI3K/Akt, MAPK, AMPK, p53, NF-κB, and Ras/RAF/MEK/ERK, which in turn triggers apoptosis, autophagy, and ROS while preventing the migration and invasion of cancer cells. We also discussed their toxicity, bioavailability, and clinical uses. ConclusionIn conclusion, galangal extract and galangin have a lot of promise for treating cancer. It is anticipated that this review will further advance the use of galangal extract and galangin as potential cancer treatment medications. Moreover, the discovery and development of drugs based on galangal has enormous potential for the therapy of cancer.

Identification of Prognostic Markers and Potential Therapeutic Targets using Gene Expression Profiling and Simulation Studies in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a 5-year relative survival rate of less than 10% making it one of the most fatal cancers. A lack of early measures of prognosis, challenges in molecular targeted therapy, ineffective adjuvant chemotherapy, and strong resistance to chemotherapy cumulatively make pancreatic cancer challenging to manage. The present study aims to enhance understanding of the disease mechanism and its progression by identifying prognostic biomarkers, potential drug targets, and candidate drugs that can be used for therapy in pancreatic cancer. Gene expression profiles from the GEO database were analyzed to identify reliable prognostic markers and potential drug targets. The disease's molecular mechanism and biological pathways were studied by investigating gene ontologies, KEGG pathways, and survival analysis to understand the strong prognostic power of key DEGs. FDA-approved anti-cancer drugs were screened through cell line databases, and docking studies were performed to identify drugs with high affinity for ARNTL2 and PIK3C2A. Molecular dynamic simulations of drug targets ARNTL2 and PIK3C2A in their native state and complex with nilotinib were carried out for 100 ns to validate their therapeutic potential in PDAC. Differentially expressed genes that are crucial regulators, including SUN1, PSMG3, PIK3C2A, SCRN1, and TRIAP1, were identified. Nilotinib as a candidate drug was screened using sensitivity analysis on CCLE and GDSC pancreatic cancer cell lines. Molecular dynamics simulations revealed the underlying mechanism of the binding of nilotinib with ARNTL2 and PIK3C2A and the dynamic perturbations. It validated nilotinib as a promising drug for pancreatic cancer. This study accounts for prognostic markers, drug targets, and repurposed anti-cancer drugs to highlight their usefulness for translational research on developing novel therapies. Our results revealed potential and prospective clinical applications in drug targets ARNTL2, EGFR, and PI3KC2A for pancreatic cancer therapy.

Quantum mechanical approaches and Molecular Docking studies of Platinum based anticancer drugs Satraplatin and Picoplatin structures.

The structures of the anticancer drug compounds satraplatin and picoplatin are optimized, and theoretical studies done by Density Functional Theory (DFT) to investigate the optical properties, global chemical descriptors, and band gap were calculated using the obtained Frontier molecular orbital values. The theoretically obtained data of the platinum drugs found to possess low energy gap values and low chemical hardness with high chemical softness describe that the compounds are chemically stable and most reactive. Using the molecular docking process, the binding mechanisms of the satraplatin and picoplatin drugs with cancer DNA structures were studied, and the results were analyzed. For the two drug compounds examined, satraplatin has shown the least binding energies at -5.06 kcal/mol compared to picoplatin at -2.69 kcal/mol, and conformations with root mean square deviation (RMSD) values by DNA structures are less than or equal to 2.00Å in targeting the specific DNA target residues of the reference bound ligand. The grid box was generated using the selective grid parameters using the Autodock 4.2 program. The drug molecules found to have the least binding energy value with the lowest inhibition constant implicate the good docking score towards the DNA structure by the docking studies. DFT studies also show good structural properties and chemical reactivity. From the obtained results, satraplatin and picoplatin were found to have good chemical descriptors and good binding affinity and are best suited for biological molecular targets.

Molecular Activities and Mechanisms of Action of Substances and Molecules from Medicinal Plants from Sub-Saharan Africa on Prostate and Cervical Cancer Cells.

Despite years of medical research, cancer remains a major public health problem worldwide, particularly in Africa. The cost, duration, and toxicity of currently available treatments are all drawbacks. Plant secondary metabolites are significant anticancer compounds. Already used in traditional health systems, plants are currently the subject of numerous studies to discover new anti-cancer drugs. This review assesses the literature on the cytotoxic effect of plant substances (extracts) and molecules on prostate and cervical cancer cell lines. PubMed, Science Direct, and Google Scholar were used to find in vitro studies carried out between 2006 and 2023 related to the cytotoxicity of extracts, substances and/or molecules from plants harvested in sub- Saharan Africa against prostate and/or cervical cancer cell lines. A total of 36 reports on the cytotoxic potential of 96 medicinal plants from sub-Saharan Africa were extracted from the selected databases. All the plants listed had a cytotoxic effect on prostate and/or cervical cancer cells. Some plant extracts or molecules showed significant activity with an IC50< 20 μg/ml. Burkina Faso and South Africa had the most plant extracts tested for prostate and cervical cancer, respectively. A total of 36 reports on the cytotoxic potential of 96 medicinal plants from sub-Saharan Africa were extracted from the selected databases.

The Use of Lipid-based Nanocarriers to Improve Ovarian Cancer Treatment: An Overview of Recent Developments.

Ovarian cancer poses a formidable health challenge for women globally, necessitating innovative therapeutic approaches. This review provides a succinct summary of the current research status on lipid-based nanocarriers in the context of ovarian cancer treatment. Lipid-based nanocarriers, including liposomes, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs), offer a promising solution for delivering anticancer drugs with enhanced therapeutic effectiveness and reduced adverse effects. Their versatility in transporting both hydrophobic and hydrophilic medications makes them well-suited for a diverse range of anticancer drugs. Active targeting techniques like ligand-conjugation and surface modifications have been used to reduce off-target effects and achieve tumour-specific medication delivery. The study explores formulation techniques and adjustments meant to enhance drug stability and encapsulation in these nanocarriers. Encouraging results from clinical trials and preclinical investigations underscore the promise of lipid-based nanocarriers in ovarian cancer treatment, providing optimism for improved patient outcomes. Notwithstanding these advancements, challenges related to clearance, long-term stability, and scalable manufacturing persist. Successfully translating lipidbased nanocarriers into clinical practice requires addressing these hurdles. To sum up, lipidbased nanocarriers are a viable strategy to improve the effectiveness of therapy for ovarian cancer. With their more focused medication administration and lower systemic toxicity, they may completely change the way ovarian cancer is treated and increase patient survival rates. Lipidbased nanocarriers need to be further researched and developed to become a therapeutically viable treatment for ovarian cancer.

Single-step purification and characterization of Pseudomonas aeruginosa azurin.

Azurin is a small periplasmic blue copper protein found in bacterial strains such as Pseudomonas and Alcaligenes where it facilitates denitrification. Azurin is extensively studied for its ability to mediate electron-transfer processes, but it has also sparked interest of the pharmaceutical community as a potential antimicrobial or anticancer agent. Here we offer a novel approach for expression and single-step purification of azurin in Escherichia coli with high yields and optimal metalation. A fusion tag strategy using an N-terminal GST tag was employed to obtain pure protein without requiring any additional purification steps. After the on-column cleavage by HRV 3C Protease, azurin is collected and additionally incubated with copper sulphate to ensure sufficient metalation. UV-VIS absorption, mass spectroscopy, and circular dichroism analysis all validated the effective production of azurin, appropriate protein folding and the development of an active site with an associated cofactor. MD simulations verified that incorporation of the N-terminal GPLGS segment does not affect azurin structure. In addition, the biological activity of azurin was tested in HeLa cells.

Synthesis and Antitumor Activity of Some New N1-(8-fluoro-4-oxoquinolin-5-yl)amidrazones.

Hydrazonoyl chloride, accessible from the respective 5-amino-8-fluoro- 4-oxoquinoline-3-carboxylate, undergoes a reaction with sec-cyclic amines to generate N1-(1- ethyl-8-fluoro-4-oxoquinolin-5-yl)amidrazone carboxylates. A novel set of N1-(1-ethyl-8-fluoro-4-oxoquinolin-5-yl)amidrazone carboxylates (7a-h) incorporating N-piperazines or related congeners was synthesized via interaction of the hydrazonoyl chloride (6), accessible from the respective 5-amino-8-fluoro-4-oxoquinoline-3-carboxylate, with the appropriate sec-cyclic amine. These new compounds were characterized by 1HNMR, 13C-NMR, and HRMS spectral data and screened for their anticancer activities. This study aimed at the synthesis of novel N1-( 4-oxoquinolin-5-yl)amidrazone carboxylate derivatives and investigated their potential as anticancer agents. The reaction of hydrazonoyl chloride with the appropriate sec-cyclic amine was applied to synthesize a novel set of N1-(1-ethyl-8-fluoro-4-oxoquinolin-5- yl)amidrazone carboxylates that incorporate N piperazines. A direct reaction of piperazines and related sec-cyclic amines with N-(4-oxoquinolin-5- yl)nitrile imine (1,3-dipole) was carried out for 8-10 h. The 1,3-dipole, generated in situ from its hydrazonoyl chloride precursor in the presence of trimethylamine, is suitable for the facile synthesis of N1-(1-ethyl-8-fluoro-4-oxoquinolin-5- yl)amidrazone carboxylates. This study led to the successful synthesis of novel N1-(8-fluoro-4-oxoquinolin-5- yl)amidrazones. All the examined compounds showed moderate activity with reasonable IC50 values in the micromolar range compared to Doxorubicin.

Insight in Quinazoline-based HDAC Inhibitors as Anti-cancer Agents.

Cancer remains a primary cause of death globally, and effective treatments are still limited. While chemotherapy has notably enhanced survival rates, it brings about numerous side effects. Consequently, the ongoing challenge persists in developing potent anti-cancer agents with minimal toxicity. The versatile nature of the quinazoline moiety has positioned it as a pivotal component in the development of various antitumor agents, showcasing its promising role in innovative cancer therapeutics. This concise review aims to reveal the potential of quinazolines in creating anticancer medications that target histone deacetylases (HDACs).

Broussoflavonol F exhibited anti-proliferative and anti-angiogenesis effects in colon cancer via modulation of the HER2-RAS-MEK-ERK pathway

BackgroundA prenylated flavonoid, broussoflavonol F (BFF), was isolated from Macaranga genus with cytotoxicities against various cancer cells, though its underlying mechanisms have not been fully elucidated. HypothesisThis study aimed to investigate the anti-tumor and anti-angiogenesis activities of BFF and its underlying mechanisms in colon cancer. MethodIn the in vitro study, the cytotoxic effects of BFF in human colon cancer HCT-116 and LoVo cells were examined using MTT assay, BrdU assay and colony formation assay. The anti-proliferative effects of BFF in these cells were assessed via cell apoptosis and cell cycle analysis using flow cytometry. The anti-angiogenesis effects of BFF in human endothelial HEMC-1 cells were also detected using scratch wound healing assay and tube formation assay. While the in vivo effects of BFF in colon cancer were further examined in zebrafish embryos and HCT116 tumor-bearing mice. The underlying mechanisms of BFF were predicted using network pharmacology analysis, and Western blotting was performed to validate both in vitro and in vivo results. ResultsBFF exhibited cytotoxicities on 5 colon cancer cell lines, as well as anti-proliferative activities via inducing apoptosis and cell cycle arrest at the G0/G1 phase in HCT116 and LoVo cells. BFF at 1.25-5 µM also suppressed cell proliferation in these two colon cancer cell lines by downregulating HER2, RAS, p-BRAF, p-MEK and p-Erk protein expressions. In addition, BFF at 2.5-5 µM could significantly decrease the length of subintestinal vessels of zebrafish embryos through decreasing mRNA expressions of NRP1a, PDGFba, PDGFRb, KDR, FLT1 and VEGRaa. Besides, BFF exhibited anti-angiogenesis activity via inhibiting cell proliferation, motility and tube formation in HMEC-1 cells. Furthermore, intraperitoneal administration of BFF (10 mg/kg) suppressed tumor growth and decreased the expression of tumor proliferation marker Ki-67 and angiogenesis marker CD31 in the tumor tissues in HCT116 tumor-bearing mice. BFF treatment could also significantly decrease expressions of RAS, p-BRAF, p-MEK and p-Erk in the tumor section, which are consistent with the in vitro results. ConclusionsThis study revealed the anti-tumor and anti-angiogenesis effects of BFF in colon cancer. This is the first report of the in vitro and in vivo anti-proliferative activity of BFF in colon cancer through regulating the HER2-RAS-MEK-ERK pathway. These findings further support the research development of BFF as an anti-cancer agent in colon cancer.

Developing new anticancer agents: Design, synthesis, biological evaluation and in silico study of several functionalized pyrimidine-5-carbonitriles as small molecules modulators targeting breast cancer

Developing new anticancer agents: Design, synthesis, biological evaluation and in silico study of several functionalized pyrimidine-5-carbonitriles as small molecules modulators targeting breast cancer

Engineering sodium alginate microparticles with different crystallinities for niclosamide repositioning and solubilization to improve solubility and oral bioavailability in rats

Niclosamide is a commonly used anthelmintic; however, its poor aqueous solubility limits its oral bioavailability. Enhancing its solubility and oral bioavailability is crucial for its repositioning as an anticancer agent. Here, we aimed to develop new sodium alginate–poloxamer microparticles with different crystallinities to increase drug solubility and oral bioavailability. Sodium alginate and poloxamer were used as the polymer and surfactant, respectively, to prepare niclosamide-loaded microparticles via spray drying. The optimized amorphous and crystalline microparticles were prepared with niclosamide/sodium alginate/poloxamer weight ratios of 1:2.5:3 and 1:1.125:0.375, respectively. Their solubilities, dissolution rates, physicochemical properties, and oral bioavailabilities were compared with those of drug powder in rats. Physicochemical characterization of the developed particles revealed changed structure from crystalline to amorphous, with no irregular crystalline characteristics but decreased particle size. Compared to the pure drug powder, crystalline microparticles retained their crystalline nature with no significant changes in particle size. Both microparticles showed significantly higher aqueous solubilities, dissolution rates, and oral bioavailabilities than niclosamide powder in rats. Amorphous microparticles showed higher solubility (approximately 1775-fold) and oral bioavailability (approximately 5.6-fold) than niclosamide powder due to the crystalline-to-amorphous change and decreased particle size. The developed amorphous microparticles can be used to improve niclosamide solubility and oral bioavailability.

Green RP-HPLC method for simultaneous quantification of epigallocatechin-3-gallate and rosmarinic acid in lipid-based nanocarriers and biological fluids: Quality by Design-driven optimization and lean six sigma approach

This study presents the development and validation of a reverse-phase high-performance liquid chromatography (RP-HPLC) method for concurrent quantification of EGCG and RA in prepared lipid-based nanocarriers and biological fluids using a QbD approach, greenness assessment, and Six-Sigma methodology. Initially, variations in critical analytical attributes were identified using the Ishikawa fishbone diagram and Risk Priority Number scores. A Taguchi Orthogonal Array design was employed to screen the critical method parameters influencing method development. Systematic optimization of the RP-HPLC method was subsequently achieved using a Box-Behnken design, with the % organic phase, flow rate, and column temperature as the variables. The responses were retention time, tailing factor, and theoretical plates for both EGCG and RA. Chromatographic separation was accomplished with a methanol and 0.1% formic acid (60:40) isocratic flow system on a Phenomenex Luna C18 column (4.6 × 250 mm, 5 μm) at a 1 mL/min flow rate. The method was rigorously validated according to ICH guidelines. Linearity was observed over a concentration range of 2 to 10 µg/mL for both EGCG and RA, yielding correlation coefficients of 0.998 and 0.999, respectively. The LOD and LOQ were determined to be 0.51 µg/mL and 1.54 µg/mL for EGCG, and 0.35 µg/mL and 1.07 µg/mL for RA. Moreover, the %RSD for all validation parameters were consistently below 2%. Forced degradation studies were conducted under acidic, basic, oxidative, and photolytic conditions to elucidate potential degradation pathways and identify degradation products. The developed method was applied to estimate EGCG and RA in prepared lipid-based nanocarriers and biological fluids like blood plasma and urine. Recovery assays in lipid-based nanocarriers, plasma, and urine samples demonstrated excellent recoveries (96.2–102.1%). The method's greenness was assessed using various tools, and its accuracy was evaluated using Six Sigma methodology. Overall, the developed HPLC method offers a rapid, sensitive, and reliable approach for quantifying EGCG and RA, laying the groundwork for their further investigation as anticancer agents, alone and in combination therapies.

Exploring the Potential Role of Phytopharmaceuticals in Alleviating Toxicities of Chemotherapeutic Agents.

Chemotherapy is the mainstay of cancer treatment, bringing patients optimism about recurrence and survival. However, the clinical effectiveness of chemotherapeutic drugs is frequently jeopardized by their intrinsic toxicity, resulting in side effects affecting the quality of life of cancer patients. This analysis explores the ethnopharmacological impact of phytopharmaceuticals, highlighting their traditional use in many cultures. The present study, which takes its cues from indigenous knowledge, aims to close the knowledge gap between traditional medicine and modern medicine in reducing the toxicities of chemotherapy treatments. The present in-depth study aims to highlight the current research and upcoming developments in phytopharmaceuticals for reducing the toxicity of chemotherapeutic drugs. Further, we address the mechanisms through which phytopharmaceuticals may reduce chemotherapy-induced side effects that include nausea, vomiting, myelosuppression, nephropathy, neuropathy, and cardiotoxicity using data from a variety of preclinical and clinical investigations. The literature search was carried out by employing search engines such as PubMed and Google Scholar with keywords such as cancer, chemotherapy, CNS toxicity, hematopoietic toxicity, renal toxicity, GI toxicity, CNS toxicity, and phytopharmaceuticals. Bioactive chemicals found in plants, such as fruits, vegetables, herbs, and spices, are being studied for their capacity to improve the safety and acceptability of chemotherapy regimens. The current review also dives into the investigation of phytopharmaceuticals as adjuvant medicines in cancer treatment, which is a viable path for addressing the pressing need to lessen chemotherapy-induced toxicities. The present review revealed that the potential of phytopharmaceuticals in alleviating chemotherapeutic drug toxicities would pave the way for better cancer treatment and patient outcomes, harmonizing with the larger trend towards personalized and holistic approaches to chemotherapy.

Necroptosis and autophagy in cisplatinum-triggered nephrotoxicity: Novel insights regarding their prognostic and diagnostic potential

Necroptosis is an innovative class of programmed autophagy (Atg) and necrosis; considered as a type of homeostatic housekeeping machinery that have observed an escalating concern due to its power in alleviating Cisplatinum-induced nephrotoxicity. This article elucidated in details the prospective role of both autophagy and necroptosis on Cisplatinum-triggered nephrotoxicity and investigating more potent therapy via lactoferrin and Ti-NPS conjugation. Cisplatinum is a commonly used chemotherapeutic drug; one of the limiting adverse actions of cisplatinum is renal toxicity. Upon cisplatinum administration, autophagy is highly stimulated in the kidney to shield against nephrotoxicity. Atg is a lysosomal degradation process which discards detorirated proteins to retain cell homeostasis. This article summarizes necroptosis progress in reconizing cisplatinum nephrotoxicity and debates how this progress can help in discovering more potent therapy via lactoferrin and Ti-NPS conjugation via monitoring autophagy and apoptotic biomarkers X-box-binding protein 1 (XBP), C/EBP homologous protein (CHOP), hypoxanthine phosphoribosyltransferase-1 (HPRT), FKBP prolyl isomerase 1B (FKBP), Cellular myelocytomatosis oncogene (C-myc), tumor suppressor gene (P53) and tumor necrosis factor (TNF-α). Cisplatinum nephrotoxicity was conducted in rat model via an oral dose of (2mg/kg BW) for one month furthermore a comparative study was conducted among TiNPs-loaded Cisplatinum and Lactoferrin loaded Cisplatinum. Loaded drug delivery system counteracted Cisplatinum triggered nephrotoxicity via controlling autophagy and apoptotic XBP, CHOP, HPRT, FKBP, C-myc, P53 and TNF-α signaling pathway.

Integrating Single-cell and Bulk RNA-seq to Construct a Metastasis-related Model for Evaluating Immunotherapy and Chemotherapy in Uveal Melanoma.

Metastasis is a major cause of death in UM, highlighting the need to use highly specific and sensitive prognostic markers to identify patients with a risk of developing metastasis. The aim of this study was to improve the current precision treatment for patients with metastatic uveal melanoma (UM). The objective of this work was to investigate the heterogeneity between primary human UM and metastatic UM at the single-cell level and to discover potential molecules regulating UM metastasis. Seurat R toolkit was employed to analyze single-cell sequencing data of UM and to identify differentially expressed genes (DEGs) between primary and metastatic UM. Least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were performed on the DEGs from the bulk RNA-seq cohort to develop a prognostic model. Based on the model, patients were divided into high and low groups. The correlations among the risk score, immune indicators, immune checkpoint blockade (ICB) therapy, and anti-tumor drug therapy were analyzed. Cell types in primary UM and metastatic UM tumors include B/plasma cells, endothelial cells, melanocytes, monocytes/macrophages, photoreceptor cells, and T cells. Among 157 DEGs between the two tumor types, S100A4, PDE4B, CHCHD10, NSG1, and C4orf48 were selected to construct a prognostic model. The model could accurately and independently predict response to ICB treatment and sensitivity to antineoplastic drugs for UM patients as well as their immune infiltration levels, risk of death, and metastasis possibility. This study analyzed the tumor ecosystem of primary and metastatic UM, providing a metastasis-related model that could be used to evaluate the prognosis, risk of metastasis, immunotherapy, and efficacy of antineoplastic drug treatment of UM.

Strategic and Innovative Roles of lncRNAs Regulated by Naturally-derived Small Molecules in Cancer Therapy.

In the field of precision and personalized medicine, the next generation sequencing method has begun to take an active place as genome-wide screening applications in the diagnosis and treatment of diseases. Studies based on the determination of the therapeutic efficacy of personalized drug use in cancer treatment in the size of the transcriptome and its extension, lncRNA, have been increasing rapidly in recent years. Targeting and/or regulating noncoding RNAs (ncRNAs) consisting of long noncoding RNAs (lncRNAs) are promising strategies for cancer treatment. Within the scope of rapidly increasing studies in recent years, it has been shown that many natural agents obtained from biological organisms can potentially alter the expression of many lncRNAs associated with oncogenic functions. Natural agents include effective small molecules that provide anti-cancer effects and have been used as chemotherapy drugs or in combination with standard anti-cancer drugs used in routine treatment. In this review, it was aimed to provide detailed information about the potential of natural agents to regulate and/or target non-coding RNAs and their mechanisms of action to provide an approach for cancer therapy. The discovery of novel anti-cancer targets and subsequent development of effective drugs or combination strategies that are still needed for most cancers will be promising for cancer treatment.