Cancer Cells Research Articles

Effects of sinomenine on a rat orthotopic liver carcinoma model.

Liver carcinoma is a common malignant tumor. In this study, an orthotopic liver carcinoma model was established by B-ultrasound, and the therapeutic effect of sinomenine (Sin) on the disease was investigated. SD rats were randomly divided into control, Sin, Sorafenib (Sor), and combination (Sin+Sor) groups (n=8). An orthotopic liver carcinoma model was established by inoculating N1-S1 cells into the rat liver by B-ultrasound-guided, and tumor volume was monitored three times by B-ultrasound after inoculation. After drug treatment, the tumor tissues were stained with HE and TUNEL, and the levels of inflammatory cytokines, ALT and AST were detected by ELISA. The numbers of erythrocytes, leukocytes and platelets were detected. Immunohistochemistry and immunofluorescence were used to detect the expression of Ki-67, CD44, VEGF and CD31. The levels of cell cycle, apoptosis-related proteins were detected by western blot. B-ultrasound monitoring found that Sin reduced tumor volume. Moreover, Sin improved tissue lesions, and promoted cancer cell apoptosis. Sin decreased the levels of inflammatory cytokines, AST and ALT, and decreased the numbers of erythrocytes, leukocytes and platelets. Simultaneously, the expressions of Ki-67, CD44, VEGF and CD31 were decreased in the Sin group. Furthermore, Sin decreased the Bcl-2, Cyclin D1, CDK4, CDK6 and Survivin levels, but increased Bax, Cleaved-caspase3/pro-caspase3, P21 and P27 levels. More importantly, the combination of Sin and Sor treatment was more effective than treatment alone. A rat orthotopic liver carcinoma model was established under the guidance of B-ultrasound, and Sin had a therapeutic effect on orthotopic liver carcinoma.

Pachyman alleviates cognitive impairment after sevoflurane anesthesia in gastric cancer surgery

Cancer cell metastasis has already taken place in most of the gastric cancer (GC) patients when diagnosed. Despite that surgery effectively delays the development of GC, sevoflurane anesthetic during surgery tends to cause cognitive impairment. Previous studies have depicted anti-tumor and neuroprotective effects of pachyman. Therefore, this study aimed at investigating a potential mechanism whereby pachyman alleviates cognitive impairment after sevoflurane anesthesia in GC surgery. A rat model of GC was constructed and received treatment with pachyman at different concentrations and caspase-3 inhibitor and agonist. After treatment, the level of inflammatory factors was detected by ELISA. Flow cytometer and Morris water maze were conducted to assess cell death and cognitive function, followed by HE gastric histopathological staining. In addition, RT-qPCR and Western blot detected GSH-PX and caspase-3 expression. Pachyman positively induced the apoptosis of GC cells and strengthened the cognitive function of rats with downregulated caspase-3. Moreover, caspase-3 inhibitor also accelerated apoptosis and improved rat cognitive function. When caspase-3 was inhibited, the level of GSH-PX was elevated. Combination of pachyman and caspase-3 inhibitor more significantly induced GC cell apoptosis and alleviated cognitive impairment. Pachyman alleviates the cognitive impairment caused by sevoflurane anesthesia in GC rats and induces tumor cell apoptosis through down-regulation of caspase-3 and up-regulation of GSH-PX.

Naringenin-induced Oral Cancer Cell Apoptosis Via ROS-mediated Bid and Bcl-xl Signaling Pathway.

Oral cancer is a malignant tumor with a high impact and poor prognosis. Naringenin, a flavonoid found in citrus fruits and its anti-inflammatory and antioxidant properties offer potential therapeutic benefits. However, limited studies have been conducted on the impact of naringenin on human tongue carcinoma CAL-27 cells. This study aims to elucidate the correlation between naringenin and tongue cancer, thereby identifying a potential therapeutic candidate for drug intervention against tongue cancer. The effect of naringenin on the apoptosis of CAL-27 cells and its mechanism were studied by cell counting kit-8, mitochondrial membrane potential assay with JC-1, Annexin V-- FITC apoptosis detection, cell cycle, and apoptosis analysis, Reactive Oxygen Species assay and Western blot. The results showed that naringenin significantly induced apoptosis in CAL-27 cells in a dose-dependent manner. Mechanistically, naringenin-induced apoptosis was mediated through the upregulation of Bid and downregulation of Bcl-xl, which led to increased generation of ROS. The findings suggested that naringenin may represent a promising candidate for the treatment of oral cancer by inducing apoptotic cell death via modulation of the Bid and Bcl-xl signaling pathways.

Tabersonine Induces the Apoptosis of Human Hepatocellular Carcinoma In vitro and In vivo.

Tabersonine, a natural indole alkaloid derived from Apocynaceae plants, exhibits antiinflammatory and acetylcholinesterase inhibitory activities, among other pharmacological effects. However, its anti-tumor properties and the underlying molecular mechanisms remain underexplored. The present study aims to investigate the anti-tumor effects of tabersonine and its mechanisms in inducing apoptosis in hepatocellular carcinoma. The inhibitory effects of tabersonine on the viability and proliferation of liver cancer cells were evaluated using MTT assay and colony formation assay. AO/EB, Hoechst, and Annexin V-FITC/ PI staining techniques were employed to observe cell damage and apoptosis. JC-1 staining was used to detect changes in mitochondrial membrane potential. Western blot analysis was conducted to study the anti-tumor mechanism of tabersonine on liver cancer cells. Additionally, a xenograft model using mice hepatoma HepG2 cells was established to assess the anti-tumor potency of tabersonine in vivo. Our findings revealed that tabersonine significantly inhibited cell viability and proliferation, inducing apoptosis in liver cancer cells. Treatment with tabersonine inhibited Akt phosphorylation, reduced mitochondrial membrane potential, promoted cytochrome c release from mitochondria to the cytoplasm, and increased the ratio of Bax to Bcl-2. These findings suggested that tabersonine induces apoptosis in liver cancer cells through the mitochondrial pathway. Furthermore, tabersonine treatment activated the death receptor pathway of apoptosis. In vivo studies demonstrated that tabersonine significantly inhibited xenograft tumor growth. Our study is the first to demonstrate that tabersonine induces apoptosis in HepG2 cells through both mitochondrial and death receptor apoptotic pathways, suggesting its potential as a therapeutic agent candidate for hepatic cancer.

Asiaticoside promoted ferroptosis and suppressed immune escape in gastric cancer cells by downregulating the Wnt/β-catenin pathway

BackgroundOur previous study has revealed that asiaticoside (AC) promotes endoplasmic reticulum stress and antagonizes proliferation and migration of gastric cancer (GC) via miR-635/HMGA1 axis. However, the effect and mechanism of AC on other progressions of GC, such as ferroptosis and immune escape, are still unknown. MethodsAGS and HGC27 cells were incubated with 1, 2 and 4 μM of AC for 24 h. Mice xenografted with AGS cells were intragastrically injected with AC. The effect and mechanism of AC on GC were determined by the measurement of the ferrous iron level, the ROS level and the glutathione peroxidase (GSH) content, flow cytometry, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry and western blotting assays. ResultsAC increased the Fe2+ level and the ROS level, but decreased the expression of GPX4 and SLC7A11 and the GSH level. Besides, AC enhanced the percent of CD8+ T cells and the IFN-γ concentration, but reduced the PD-L1 expression and the IL-10 level. Mechanically, AC downregulated the relative levels of β-catenin, active-β-catenin, p-GSK3β/GSK3β, cyclin D1 and c-Myc in GC cells, which were rescued with the application of LiCl (an activator of Wnt/β-catenin pathway) in AGS cells. Moreover, activation of Wnt/β-catenin pathway by LiCl or the β-catenin overexpression inverted the effect of AC on ferroptosis and immune escape in GC cells. In vivo, AC treatment declined the tumor size and weight, the level of GPX4, SLC7A11, PD-L1 and IFN-γ, and the expression of Wnt/β-catenin pathway. ConclusionAC enhanced ferroptosis and repressed immune escape by downregulating the Wnt/β-catenin signaling in GC.

Super-Resolution Ultrasound Imaging for Monitoring the Therapeutic Efficacy of a Vascular Disrupting Agent in an Animal Model of Breast Cancer.

Evaluate the use of super-resolution ultrasound (SRUS) imaging for the early detection of tumor response to treatment using a vascular-disrupting agent (VDA). A population of 28 female nude athymic mice (Charles River Laboratories) were implanted with human breast cancer cells (MDA-MB-231, ATCC) in the mammary fat pad and allowed to grow. Ultrasound imaging was performed using a Vevo 3100 scanner (FUJIFILM VisualSonics Inc) equipped with the MX250 linear array transducer immediately before and after receiving bolus injections of a microbubble (MB) contrast agent (Definity, Lantheus Medical Imaging) via the tail vein. Following baseline ultrasound imaging, VDA drug (combretastatin A4 phosphate, CA4P, Sigma Aldrich) or control saline was injected via the placed catheter. After 4 or 24 hours, repeat ultrasound imaging along the same tumor cross-section occurred. Direct intratumoral pressure measurements were obtained using a calibrated sensor. All raw ultrasound data were saved for offline processing and SRUS image reconstruction using custom MATLAB software (MathWorks Inc). From a region encompassing the tumor space and the entire postprocessed ultrasound image sequence, time MB count (TMC) curves were generated in addition to traditional SRUS maps reflecting MB enumeration at each pixel location. Peak enhancement (PE) and wash-in rate (WIR) were extracted from these TMC curves. At termination, intratumoral microvessel density (MVD) was quantified using tomato lectin labeling of patent blood vessels. SRUS images exhibited a clear difference between control and treated tumors. While there was no difference in any group parameters at baseline (0 hour, P > .09), both SRUS-derived PE and WIR measurements in tumors treated with VDA exhibited significant decreases by 4 (P = .03 and P = .05, respectively) and 24 hours (P = .02 and P = .01, respectively), but not in control group tumors (P > .22). Similarly, SRUS derived microvascular maps were not different at baseline (P = .81), but measures of vessel density were lower in treated tumors at both 4 and 24 hours (P < .04). An inverse relationship between intratumoral pressure and both PE and WIR parameters were found in control tumors (R2 > .09, P < .03). SRUS imaging is a new modality for assessing tumor response to treatment using a VDA.

Chemical composition, antioxidant, antimicrobial and anticancer activities of endemic Cephalaria tuteliana

IntroductionThe genus Cephalaria, belonging to the Caprifoliaceae family, is a rich source of secondary metabolites, including mainly saponins which display a variety of biological activities, such as antimicrobial, antioxidant, and anticancerous effects. This study was carried out to observe the biochemical composition and to evaluate the biological activities of Cephalaria tuteliana Kus & Gokturk. MethodsThe composition of endemic C. tuteliana was determined through gas chromatography-mass spectrometry (GC-MS) studies. Antimicrobial effect were determined by the disk diffusion and dilution methods for test bacteria and test fungi. The antioxidant potential of the ethanol extract was also investigated. Cell proliferation and apoptosis analysis were investigated by WST-1 and ELISA methods. The migration level of PC-3 prostate cancer cells after plant extract application was examined by wound healing assay. Also, molecular docking experiments were performed to investigate the anticancer activity of the major component found in the C.tuteliana extract. ResultsGC-MS analysis showed that the predominant compounds were Phenol, 2,2′-methylenebis [6-(1,1dimethyl ethyl)-4-methyl- (23.54%), 9,12,15-octadecatrien-1-ol, (Z,Z,Z)-(6.06%) and n-Hexadecanoic acid (3.03%). The ethanolic extract of C. tuteliana displayed moderate antimicrobial activity against a spectrum of tested microorganisms. Also, it exhibited significant antiproliferative effects on PC-3 human prostate cancer cells while having no harmful effects on healthy control HUVEC cells. Furthermore, enhanced expressions of Caspase-3, 8, and 9 were observed in PC-3 cells after plant extract treatment. Also, cell migration level was notably reduced, especially at a dose of 400 µg/mL in PC-3 cells. The DPPH free radical scavenging activity of ethanolic extracts of C. tuteliana showed higher activity than ascorbic acid. Molecular docking experiments showed potential binding of the major aromatic compound in C.tuteliana extract to human androgen receptor 1E3G protein. ConclusionThese findings highlight the potential of C. tuteliana as a valuable natural resource and pave the way for further in vivo prostate cancer investigations.

Anti-colorectal Cancer Activity of Quinazoline Derivatives: A Comprehensive Review

Introduction and Objective: The identification of a bioactive template (or lead) is one of the important features of modern drug discovery. Natural products, synthetic and biotechnological sources, serve as important templates for the development of novel bioactive molecules. Quinazoline is one of the heterocyclic templates present in many natural and synthetic drugs and exhibits various biological activities, including anticancer, by blocking the pharmacological pathway of different targets. Methodology: In this study, the data was collected from the literature and patents to examine the anticolorectal cancer efficacy of quinazoline compounds and their mechanism of actions. According to the published literature and patents, the benzene and/or pyrimidine rings of the quinazoline have been substituted with amino groups or substituted amino groups to develop novel analogues endowed with anticancer properties. The anti-colorectal cancer activity of quinazolines was due to the flexible chain containing terminal phenyl and/or heterocyclic rings (thiazole, pyrazole, piperidine, piperazine, etc.). Results: These quinazoline derivatives were found to inhibit the growth of colorectal cancer cells by modulating the expression of specific genes and proteins involved in cancer progression, such as receptor tyrosine kinases, epidermal growth factor receptors, dihydrofolate reductase, topoisomerases, histone deacetylase, and apoptotic proteins. Conclusion: These findings suggest that the quinazoline nucleus may be exploited to identify new anticolorectal cancer agents with suitable pharmacokinetic profiles.

Nanobots: Revolutionising the Next Generation of Biomedical Technology and Drug Therapy

Abstract: Nanoscale machines called “nanorobots” that were hitherto only futuristic ideas are set to storm healthcare and pharmaceuticals with newer technologies for minimally invasive diagnosis, quick and precise surgeries, and targeted drug delivery, which is challenging to achieve by conventional drug delivery systems. Nanobots can be defined as controllable nano-sized mechanical or electromechanical devices which are easily incorporated into cells and used for a variety of cellular functions like combating bacteria and viruses, disposing away dead cells/tissue at the place of a wound, cell/tissue repair and destruction of cancer cells, and also for transporting drugs to cells. Nanorobots can help avoid the untoward effects of traditional drug delivery systems and ameliorate the efficiency of drug delivery by quickly entering the desired cells without affecting other organs. With the advent of mobile communication, artificial neural networks, and Information Technology, futuristic and more advanced nanobots with artificial intelligence are in the offing. However, the challenges to this revolutionary technology are umpteen, the major concern being their interaction inside the human body. This review explicitly expounds on nanobots and their applications to medicine, biomedical research, and drug delivery.

Cell-penetrating peptide and cationic liposomes mediated siRNA delivery to arrest growth of chronic myeloid leukemia cells in vitro

Gene silencing through RNA interference (RNAi) is a promising therapeutic approach for a wide range of disorders, including cancer. Non-viral gene therapy, using specific siRNAs against BCR-ABL1, can be a supportive or alternative measure to traditional chronic myeloid leukemia (CML) tyrosine kinase inhibitor (TKIs) therapies, given the prevalence of clinical TKI resistance. The main challenge for such approaches remains the development of the effective delivery system for siRNA tailored to the specific disease model.The purpose of this study was to examine and compare the efficiency of endosomolytic cell penetrating peptide (CPP) EB1 and PEG2000-decorated cationic liposomes composed of polycationic lipid 1,26-bis(cholest-5-en-3-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride (2Х3) and helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) for anti-bcr-abl siRNA delivery into the K562 human CML cell line. We show that both EB1 and 2Х3-DOPE-DSPE-PEG2000 (0.62 % mol.) liposomes effectively deliver siRNA into K562 cells by endocytic mechanisms, and the use of liposomes leads to more effective inhibition of expression of the targeted gene (BCR-ABL1) and cancer cell proliferation. Taken together, these findings suggest that PEG-decorated cationic liposomes mediated siRNA delivery allows an effective antisense suppression of certain oncogenes, and represents a promising new class of therapies for CML.

Decoding long non‑coding RNAs: Friends and foes in cancer development (Review).

Cancer remains a formidable adversary, challenging medical advancements with its dismal prognosis, low cure rates and high mortality rates. Within this intricate landscape, long non‑coding RNAs (lncRNAs) emerge as pivotal players, orchestrating proliferation and migration of cancer cells. Harnessing the potential of lncRNAs as therapeutic targets and prognostic markers holds immense promise. The present comprehensive review delved into the molecular mechanisms underlying the involvement of lncRNAs in the onset and progression of the top five types of cancer. By meticulously examining lncRNAs across diverse types of cancer, it also uncovered their distinctive roles, highlighting their exclusive oncogenic effects or tumor suppressor properties. Notably, certain lncRNAs demonstrate diverse functions across different cancers, confounding the conventional understanding of their roles. Furthermore, the present study identified lncRNAs exhibiting aberrant expression patterns in numerous types of cancer, presenting them as potential indicators for cancer screening and diagnosis. Conversely, a subset of lncRNAs manifests tissue‑specific expression, hinting at their specialized nature and untapped significance in diagnosing and treating specific types of cancer. The present comprehensive review not only shed light on the intricate network of lncRNAs but also paved the way for further research and clinical applications. The unraveled molecular mechanisms offer a promising avenue for targeted therapeutics and personalized medicine, combating cancer proliferation, invasion and metastasis.

Recent Advances on PKM2 Inhibitors and Activators in Cancer Applications.

Metabolic reprogramming of cells, from the normal mode of glucose metabolism named glycolysis, is a pivotal characteristic of impending cancerous cells. Pyruvate kinase M2 (PKM2), an important enzyme that catalyzes the final rate-limiting stage during glycolysis, is highly expressed in numerous types of tumors and aids in development of favorable conditions for the survival of tumor cells. Increasing evidence has suggested that PKM2 is one of promising targets for innovative drug discovery, especially for the developments of antitumor therapeutics. Herein, we systematically summarize the recent advancement on PKM2 modulators including inhibitors and activators in cancer applications. We also discussed the classifications of pyruvate kinases in mammals and the biological functions of PKM2 in this review. We do hope that this review would provide a comprehensive understanding of the current research on PKM2 modulators, which may benefit the development of more potent PKM2-related drug candidates to treat PKM2-associated diseases including cancers in future.

Dietary Phytoactives in the Management of Gastric Cancer - A Mini Review

Abstract: Gastric cancer is the fourth leading cause of morbidity worldwide and is known to affect various gastric organs, including the esophagus, intestine, colon, and pancreas. There are variable factors responsible for the development of gastric tumors, such as environmental factors, EPV, hepatitis B and C, and other genetic factors. Phytoactives, or secondary metabolites of plants, have a wide range of biological impacts, including the capacity to prevent cancer in humans. They have this anticancerous impact because of their multi-target mechanism of action, which also includes antioxidant, anti-proliferative, cell apoptosis, and anti-mutagenic effects. To epitomize the role of vital dietary phytoactives as a new approach for treating gastric cancer and explains various mechanisms for their anticancerous activity. H. pylori-associated gastric tumors are the most common, and Phytoactives such as curcumin, piperine, walnut oil, tea, and others possess anticancer properties. They have shown anticancer activity against gastric tumor cell lines via different mechanisms like cell cycle arrest, apoptosis, inhibition of cell proliferation, adhesion, colonization of cancer cells, inhibition of inflammatory mediators, tumor cell bioenergetics, up and down-regulation of various gene and protein expression, and chelation and scavenging of ROS.

Curcuminoids as cell signaling pathway modulators: A potential strategy for cancer prevention.

Despite substantial advancements in curative modern medicine in the last few decades, cancer risk and casualty rates have continued to mount globally. The exact reason for cancer's onset and progression is still unknown. However, skeletal and functional abnormalities in the genetic code are assumed to be the primary cause of cancer. Many lines of evidences reported that some medicinal plants can be utilized to curb cancer cell proliferation with a safe, fruitful, and cost-efficient perspective. Curcuminoids, isolated from Curcuma longa, have gotten a lot of focus due to their anticancer potential as they reduce tumor progression, invasion, and dissemination. Further, they modulated signal transduction routes like MAPK, PI3K/Akt/mTOR, JAK/STAT, and Wnt/β-catenin, etc., and triggered apoptosis as well as actuated autophagy in malignant cells without altering the normal cells, thus preventing cancer progression. Besides, Curcuminoids also regulate the function and expression of anti-tumor and carcinogenic miRNAs. Clinical studies also reported the therapeutic effect of Curcuminoids against various cancer through decreasing specific biomarkers like TNF-α, Bcl-2, COX-2, PGE2, VEGF, IκKβ, and various cytokines like IL-12p70, IL-10, IL-2, IFN-γ levels and increasing in p53 and Bax levels. Thus, in the present review, we abridged the modulation of several signal transduction routes by Curcuminoids in various malignancies, and its modulatory role in the initiation of tumor-suppressive miRNAs and suppression of the oncogenic miRNAs are explored. Additionally, various pharmacokinetic approaches have been projected to address the Curcuminoids bioavailability like the use of piperine as an adjuvant; nanotechnology-based Curcuminoids preparations utilizing Curcuminoids analogues are also discussed.

Fumonisin B1 protects against long-chained polyunsaturated fatty acid-induced cell death in HepG2 cells – implications for cancer promotion

Fumonisin B1 (FB1), a food-borne mycotoxin, is a cancer promoter in rodent liver and augments proliferation of initiated cells while inhibiting the growth of normal hepatocytes by disrupting lipid biosynthesis at various levels. HepG2 cancer cells exhibited resistance to FB1-induced toxic effects presumably due to their low content of polyunsaturated fatty acids (PUFA) even though FB1-typical lipid changes were observed, e.g. significantly increased phosphatidylethanolamine (PE), decreased sphingomyelin and cholesterol content, increased sphinganine (Sa) and sphinganine/sphingosine ratio, increased C18:1ω9, decreased C20:4ω6 content in PE and decreased C20:4ω6-PC/PE ratio. Increasing PUFA content of HepG2 cells with phosphatidylcholine (PC) vesicles containing C20:4ω6 (SAPC) or C22:6ω6 (SDPC) disrupted cell survival, cellular redox status and induced oxidative stress and apoptosis. A partially protective effect of FB1 was evident in PUFA-enriched HepG2 cells which may be related to the FB1-induced reduction in oxidative stress and the disruption of key cell membrane constituents indicative of a resistant lipid phenotype. Interactions between different ω-6 and ω-3 PUFA, membrane constituents including cholesterol, and the glycerophospho- and sphingolipids and FB1 in this cell model provide further support for the resistant lipid phenotype and its role in the complex cellular effects underlying the cancer promoting potential of the fumonisins.

Application of MicroRNA-124-Loaded Liposome Nanoparticles for Suppressing Pancreatic Cancer Cell Progression and Restraining Autophagy Through Targeting BECN1

This study determines the efficacy of microRNA (miR)-124-loaded liposome nanoparticles on pancreatic cancer (PC). Herein, pancreatic cells were co-cultured with miR-124-loaded nanoparticles, pure liposome nanoparticles (empty vector group) or cultured alone (control group). The cells were administered with BECN1 inhibitor, and negative controls. The expression of autophagy-related factors (BECN1, P62, LC3) was determined by Western blot and cancer cell migration capacity was assessed by Transwell assay. The relation of miR-124 with BECN1 was assessed by bioinformatics analysis and dual-luciferase reporter gene assay. Compared with control group and the empty vector group, treatment with miR-124-loaded nanoparticles resulted in reduced number of migrated cells, scratch rate, and decreased expression of BECN1, P62, and LC3 (P &lt; 0.05) without difference between control group and empty vector group (P &gt; 0.05). Additional administration of BECN1 inhibitor further decreased migration and invasion of PC cells and obtained lower level of BECN1, P62, and LC3 protein, which was significantly lower than control group and miR-124+BECN1 NC group (P &lt; 0.05). miR-124+BECN1 NC group exhibited lower expressions of BECN1, P62, and LC3 than control group (P &lt; 0.05). Mechanistically, miR-124 targeted BECN1 to influence biological behaviors of PC cells. There is a target relationship between miR-124 and BECN1 in PC. miR-124-loaded nanoparticles incorporated with BECN1 inhibitor restrained autophagy through down-regulation of BECN1, P62, and LC3 and suppressed PC cell invasion and migration. These findings provide a novel insight into targeted therapy for PC.

Naringenin-Loaded Bovine Serum Albumin Nanoparticles Inhibit Reactive Oxygen Species (ROS) to Prevent Ulcer and Gastric Cancer

Gastric cancer is a malignance of digestive system and effective treatment measures are key to treatment of gastric cancer. In this experiment, we assessed the effect of bovine serum albumin nanoparticle (BASNP)-coated naringenin (NGN) on reactive oxygen species (ROS) in gastric cancer. After preparation of NGN-BASNP and animal model of gastric cancer, rats were administered with NGN-BASNP, ROS agonists and ROS inhibitors, when the model group was set. After one week of intervention, gastric ulcers in rats were measured and Hematoxylin-eosin (HE) staining was performed. Transwell chamber was used to detect cell invasion ability, while 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was detected proliferation ability of gastric cancer cells. Real Time Quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot determined TNF-α mRNA expression and ROS. With about 100 nm diameter of NGN-BASNP nanoparticles, the nanoparticles presented in good shape. Compared with lesions in the model group, NGN-BASNP treatment greatly improved the condition, relieving the ulcer and decreasing the ulcer area (P &lt; 0.05). After adding ROS agonist, inhibitory effect of NGN-BASNP intervention was amplified (P &lt; 0.01) when the ROS level in the NGN-BASNP+ROS agonist group was decreased and TNF-α expression decreased. Moreover, NGN-BASNP effectively suppressed gastric cancer cell proliferation and migration but induced apoptosis. NGN-BASNP inhibited the expression of TNF-α mRNA and ROS level in gastric cancer cells, thereby alleviating gastric ulcer and delaying gastric cancer cell growth.

Preparation, Characterization, and Evaluation of the Anticancer Effect of Mesoporous Silica Nanoparticles Containing Rutin and Curcumin.

The aim of this study was the preparation of mesoporous silica nanoparticles co-loaded with rutin and curcumin (Rut-Cur-MSNs) and the assessment of its physicochemical properties as well as its cytotoxicity on the head and neck cancer cells (HN5). Besides, ROS generation of HN5 cells exposed to Rut-Cur-MSNs was evaluated. Several investigations showed that rutin and curcumin have potential effects as anticancer phytochemicals; however, their low aqueous solubility and poor bioavailability limited their applications. The assessment of physicochemical properties and anticancer effect of prepared nanoparticles was the objective of this study. The physicochemical properties of produced nanoparticles were evaluated. The toxicity of Rut-Cur-MSNs on HN5 cells was assessed. In addition, the ROS production in cells treated with Rut-Cur-MSNs was assessed compared to control untreated cells. The results showed that Rut-Cur-MSNs have mesoporous structure, nanometer size and negative surface charge. The X-ray diffraction pattern showed that the prepared nanoparticles belong to the family of silicates named MCM-41. The cytotoxicity of Rut-Cur-MSNs at 24 h was significantly higher than that of rutin-loaded MSNs (Rut-MSNs) and curcumin-loaded MSNs (Cur-MSNs) (p<0.05). The achieved results recommend that the prepared mesoporous silica nanoparticles containing rutin and curcumin can be a useful nanoformulation for the treatment of cancer. The produced nanomaterial in this study can be helpful for cancer therapy.

Intercontinental Comparison of Immunohistochemical Subtypes Among Individuals With Breast Cancer in South-East Asia and South America: A Scoping Systematic Review and Meta-Analysis of Observational Studies.

Breast cancer (BC) remains a significant global concern, particularly among developing countries in South-East Asia (SEA) and South America (SA). The socioeconomic burdens of oncologic care in those countries were often originated from limited accessibility on attainable therapeutic options and reliability on identifying essential information of cancer cells, i.e., immunohistochemical (IHC) subtyping to determine suitable approaches. The triple-negative breast cancer (TNBC) is among the most aggressive category in breast malignancy, therefore, requiring more specific molecular pathway blocking to exhaust the cells. However, large-scale epidemiological investigation on its rate among BC remains unavailable to date. This study aimed to describe the prevalence of TNBC in the SEA and SA continents since it may guide the future direction of oncologic research and trials. This review focuses on observational studies from the SEA and SA continents from the last decade. Each study represents its country or cities, period of observation, population size, and the TNBC-BC rate as the main outcomes. Therefore, we may also limit the reporting bias originated from same-patient data on the specific occasions. The analysis will be derived to SEA-SA comparison, plus SEA/SA-specific session as processed in Comprehensive Meta-Analysis (CMA) version 3.0. The statistical analysis will be performed in random effects model (REM) within 95% confidence interval (CI). From 46 studies included in the final analysis with a total enlisted population of 34,346 unique individuals with BC, the TNBC rate was higher in the SEA compared to the SA region (19.3% vs. 15.7%; P < 0.05 in 95% CI), with the highest prevalence observed in Vietnam (22.4%) and Peru (17.8%), if it was restricted on countries with two or more studies. Interestingly, both Laos and Argentina possessed significant differences compared to other countries within their respective continents, with the highest and lowest TNBC rates (P < 0.05). The IHC characteristics in SEA differ from those in the SA continent as mainly represented by TNBC prevalence, possibly shaping the course of future trials in the respective region based on IHC expressivity status.

Development of a PAK4-targeting PROTAC for renal carcinoma therapy: concurrent inhibition of cancer cell proliferation and enhancement of immune cell response

Development of a PAK4-targeting PROTAC for renal carcinoma therapy: concurrent inhibition of cancer cell proliferation and enhancement of immune cell response