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1.
Nano Lett ; 23(1): 353-362, 2023 01 11.
Article in English | MEDLINE | ID: mdl-36394269

ABSTRACT

Growing evidence indicates that the tumor microenvironment (TME) can be combined with other therapeutic modalities, including cytotoxic chemotherapy and targeted therapies, to produce unanticipated results in oncology treatment. Here, we proposed a novel bacterial nanomaterial capable of targeting peritumoral biofilm and modulating TME. It was based on tetrahedral framework nucleic acids (T) that were chemically attached to aptamer AS1411 and 5-fluorouracil (AT5). Additionally, the oral pathogenic bacterium Streptococcus mutans (S.m) was employed as a biocarrier for synergetic biofilm targeting and immunomodulation. In this article, the effect of AT5-coupled S.m-derived nanocells (S.m-AT5) was investigated in vitro and in vivo. Due to bacteria aggregation in the tumor-specific biofilm, these nanocells released greater medication concentrations. Furthermore, they exerted an immunomodulatory effect by stimulating the maturation of dendritic cells (DCs) and regulation of T cells. This chemo-immunostimulation combination has a powerful antitumor impact. It may also be an advanced approach for boosting the survival rate of cancer patients.


Subject(s)
Immunomodulation , Neoplasms , Humans , Neoplasms/drug therapy , Neoplasms/metabolism , Biofilms , Streptococcus mutans/metabolism , Tumor Microenvironment
2.
Cancer Immunol Immunother ; 72(7): 2045-2056, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36795124

ABSTRACT

Immunotherapy based on immune checkpoint inhibitors (ICIs) has provided revolutionary results in treating various cancers. However, its efficacy in colorectal cancer (CRC), especially in microsatellite stability-CRC, is limited. This study aimed to observe the efficacy of personalized neoantigen vaccine in treating MSS-CRC patients with recurrence or metastasis after surgery and chemotherapy. Candidate neoantigens were analyzed from whole-exome and RNA sequencing of tumor tissues. The safety and immune response were assessed through adverse events and ELISpot. The clinical response was evaluated by progression-free survival (PFS), imaging examination, clinical tumor marker detection, circulating tumor DNA (ctDNA) sequencing. Changes in health-related quality of life were measured by the FACT-C scale. A total of six MSS-CRC patients with recurrence or metastasis after surgery and chemotherapy were administered with personalized neoantigen vaccines. Neoantigen-specific immune response was observed in 66.67% of the vaccinated patients. Four patients remained progression-free up to the completion of clinical trial. They also had a significantly longer progression-free survival time than the other two patients without neoantigen-specific immune response (19 vs. 11 months). Changes in health-related quality of life improved for almost all patients after the vaccine treatment. Our results shown that personalized neoantigen vaccine therapy is likely to be a safe, feasible and effective strategy for MSS-CRC patients with postoperative recurrence or metastasis.


Subject(s)
Cancer Vaccines , Colorectal Neoplasms , Humans , Antigens, Neoplasm , Cancer Vaccines/therapeutic use , Colorectal Neoplasms/genetics , Immunotherapy/methods , Immunotherapy, Active , Microsatellite Repeats , Quality of Life
3.
Int J Mol Sci ; 24(4)2023 Feb 08.
Article in English | MEDLINE | ID: mdl-36834783

ABSTRACT

Gene therapy has attracted much attention because of its unique mechanism of action, non-toxicity, and good tolerance, which can kill cancer cells without damaging healthy tissues. siRNA-based gene therapy can downregulate, enhance, or correct gene expression by introducing some nucleic acid into patient tissues. Routine treatment of hemophilia requires frequent intravenous injections of missing clotting protein. The high cost of combined therapy causes most patients to lack the best treatment resources. siRNA therapy has the potential of lasting treatment and even curing diseases. Compared with traditional surgery and chemotherapy, siRNA has fewer side effects and less damage to normal cells. The available therapies for degenerative diseases can only alleviate the symptoms of patients, while siRNA therapy drugs can upregulate gene expression, modify epigenetic changes, and stop the disease. In addition, siRNA also plays an important role in cardiovascular diseases, gastrointestinal diseases, and hepatitis B. However, free siRNA is easily degraded by nuclease and has a short half-life in the blood. Research has found that siRNA can be delivered to specific cells through appropriate vector selection and design to improve the therapeutic effect. The application of viral vectors is limited because of their high immunogenicity and low capacity, while non-viral vectors are widely used because of their low immunogenicity, low production cost, and high safety. This paper reviews the common non-viral vectors in recent years and introduces their advantages and disadvantages, as well as the latest application examples.


Subject(s)
Hepatitis B , Nucleic Acids , Humans , RNA, Small Interfering/genetics , Genetic Therapy/methods , Hepatitis B/drug therapy , Half-Life , Genetic Vectors
4.
J Integr Neurosci ; 21(1): 32, 2022 Jan 28.
Article in English | MEDLINE | ID: mdl-35164468

ABSTRACT

Evidence suggests that there is a close association between myeloperoxidase (MPO) gene rs2333227 G>A polymorphism with Alzheimer's disease (AD) susceptibility. We conducted a meta-analysis to explore the precise association between MPO rs2333227 G>A polymorphism and AD susceptibility. Online databases were searched and the relevant information was collected. Crudeodds ratios with 95% confidence intervals were calculated. Trial sequential analysis (TSA), heterogeneity analyses, accumulative analyses, sensitivity analyses, and publication biasestests were performed. Overall, nine publications (ten independent case-controls) were included in this meta-analysis, involving 3260 participants. Pooled results revealed no significant association between MPO rs2333227 G>A polymorphism and AD susceptibility was observed. TSA showed that the present meta-analysis remained inconclusive due to insufficient evidence. In summary, the current meta-analysis indicated that the MPO rs2333227 G>A polymorphism may not be acausalfactor in the development of AD.


Subject(s)
Alzheimer Disease/genetics , Peroxidase/genetics , Genetic Predisposition to Disease , Humans , Risk
5.
Nano Lett ; 19(7): 4505-4517, 2019 07 10.
Article in English | MEDLINE | ID: mdl-31185573

ABSTRACT

DNA nanorobots have emerged as new tools for nanomedicine with the potential to ameliorate the delivery and anticancer efficacy of various drugs. DNA nanostructures have been considered one of the most promising nanocarriers. In the present study, we report a DNA framework-based intelligent DNA nanorobot for selective lysosomal degradation of tumor-specific proteins on cancer cells. We site-specifically anchored an anti-HER2 aptamer (HApt) on a tetrahedral framework nucleic acid (tFNA). This DNA nanorobot (HApt-tFNA) could target HER2-positive breast cancer cells and specifically induce the lysosomal degradation of the membrane protein HER2. An injection of the DNA nanorobot into a mouse model revealed that the presence of tFNA enhanced the stability and prolonged the blood circulation time of HApt, and HApt-tFNA could therefore drive HER2 into lysosomal degradation with a higher efficiency. The formation of the HER2-HApt-tFNA complexes resulted in the HER2-mediated endocytosis and digestion in lysosomes, which effectively reduced the amount of HER2 on the cell surfaces. An increased HER2 digestion through HApt-tFNA further induced cell apoptosis and arrested cell growth. Hence, this novel DNA nanorobot sheds new light on targeted protein degradation for precision breast cancer therapy.


Subject(s)
Aptamers, Nucleotide , Breast Neoplasms , DNA , Drug Delivery Systems , Lysosomes/metabolism , Proteolysis/drug effects , Receptor, ErbB-2/metabolism , Robotics , Animals , Aptamers, Nucleotide/chemistry , Aptamers, Nucleotide/pharmacology , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , DNA/chemistry , DNA/pharmacology , Endocytosis/drug effects , Female , Humans , Lysosomes/pathology , MCF-7 Cells , Mice , Mice, Nude , Xenograft Model Antitumor Assays
6.
Nano Lett ; 18(9): 5652-5659, 2018 09 12.
Article in English | MEDLINE | ID: mdl-30088771

ABSTRACT

One of the biggest obstacles for the use of antisense oligonucleotides as antibacterial therapeutics is their limited uptake by bacterial cells without a suitable carrier, especially in multi-drug-resistant bacteria with a drug efflux mechanism. Existing vectors, such as cell-penetrating peptides, are inefficient and nontargeting, and accordingly are not ideal carriers. A noncytotoxic tetrahedral DNA nanostructure (TDN) with a controllable conformation has been developed as a delivery vehicle for antisense oligonucleotides. In this study, antisense peptide nucleic acids (asPNAs) targeting a specific gene ( ftsZ) were efficiently transported into methicillin-resistant Staphylococcus aureus cells by TDNs, and the expression of ftsZ was successfully inhibited in an asPNA-concentration-dependent manner. The delivery system specifically targeted the intended gene. This novel delivery system provides a better platform for future applications of antisense antibacterial therapeutics and provides a basis for the development of a new type of antibacterial drug for multi-drug-resistant bacterial infections.


Subject(s)
Anti-Bacterial Agents/pharmacology , DNA, Antisense/pharmacology , Methicillin-Resistant Staphylococcus aureus/drug effects , Nanostructures/chemistry , Peptide Nucleic Acids/pharmacology , Staphylococcal Infections/drug therapy , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Bacterial Proteins/genetics , Cytoskeletal Proteins/genetics , DNA, Antisense/administration & dosage , DNA, Antisense/chemistry , Down-Regulation/drug effects , Drug Carriers/chemistry , Humans , Peptide Nucleic Acids/administration & dosage , Peptide Nucleic Acids/chemistry , Staphylococcal Infections/genetics
7.
J Am Chem Soc ; 140(37): 11820-11828, 2018 09 19.
Article in English | MEDLINE | ID: mdl-30203972

ABSTRACT

A significant challenge for solid tumor treatment is ensuring that a sufficient concentration of therapeutic agent is delivered to the tumor site at doses that can be tolerated by the patient. Biomolecular targeting can bias accumulation in tumors by taking advantage of specific interactions with receptors overexpressed on cancerous cells. However, while antibody-based immunoconjugates show high binding to specific cells, their low dissociation constants ( KD) and large Stokes radii hinder their ability to penetrate deep into tumor tissue, leading to incomplete cell killing and tumor recurrence. To address this, we demonstrate the design and production of a photo-cross-linkable affibody that can form a covalent bond to epidermal growth factor receptor (EGFR) under near UV irradiation. Twelve cysteine mutations were created of an EGFR affibody and conjugated with maleimide-benzophenone. Of these only one exhibited photoconjugation to EGFR, as demonstrated by SDS-PAGE and Western blot. Next this modified affibody was shown to not only bind EGFR expressing cells but also show enhanced retention in a 3D tumor spheroid model, with minimal loss up to 24 h as compared to either unmodified EGFR-binding affibodies or nonbinding, photo-cross-linkable affibodies. Finally, in order to show utility of photo-cross-linking at clinically relevant wavelengths, upconverting nanoparticles (UCNPs) were synthesized that could convert 980 nm light to UV and blue light. In the presence of UCNPs, both direct photoconjugation to EGFR and enhanced retention in tumor spheroids could be obtained using near-infrared illumination. Thus, the photoactive affibodies developed here may be utilized as a platform technology for engineering new therapy conjugates that can penetrate deep into tumor tissue and be retained long enough for effective tumor therapy.


Subject(s)
Antineoplastic Agents/pharmacology , Cross-Linking Reagents/pharmacology , Mammary Neoplasms, Animal/drug therapy , Protein Kinase Inhibitors/pharmacology , Animals , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cross-Linking Reagents/chemistry , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/biosynthesis , ErbB Receptors/metabolism , Female , Humans , Mammary Neoplasms, Animal/metabolism , Mammary Neoplasms, Animal/pathology , Mice , Photochemical Processes , Protein Kinase Inhibitors/chemistry , Ultraviolet Rays
8.
Opt Express ; 26(10): 13289-13300, 2018 May 14.
Article in English | MEDLINE | ID: mdl-29801354

ABSTRACT

Recently Zhang et al [ Phys. Rev. A95, 012333 (2017)] developed a new approach to estimate the failure probability for the decoy-state BB84 QKD system when taking finite-size key effect into account, which offers security comparable to Chernoff bound, while results in an improved key rate and transmission distance. Based on Zhang et al's work, now we extend this approach to the case of the measurement-device-independent quantum key distribution (MDI-QKD), and for the first time implement it onto the four-intensity decoy-state MDI-QKD system. Moreover, through utilizing joint constraints and collective error-estimation techniques, we can obviously increase the performance of practical MDI-QKD systems compared with either three- or four-intensity decoy-state MDI-QKD using Chernoff bound analysis, and achieve much higher level security compared with those applying Gaussian approximation analysis.

9.
Small ; 13(24)2017 06.
Article in English | MEDLINE | ID: mdl-28481463

ABSTRACT

DNA-mediated assembly of core-satellite structures composed of Zr(IV)-based porphyrinic metal-organic framework (MOF) and NaYF4 ,Yb,Er upconverting nanoparticles (UCNPs) for photodynamic therapy (PDT) is reported. MOF NPs generate singlet oxygen (1 O2 ) upon photoirradiation with visible light without the need for additional small molecule, diffusional photosensitizers such as porphyrins. Using DNA as a templating agent, well-defined MOF-UCNP clusters are produced where UCNPs are spatially organized around a centrally located MOF NP. Under NIR irradiation, visible light emitted from the UCNPs is absorbed by the core MOF NP to produce 1 O2 at significantly greater amounts than what can be produced from simply mixing UCNPs and MOF NPs. The MOF-UCNP core-satellite superstructures also induce strong cell cytotoxicity against cancer cells, which are further enhanced by attaching epidermal growth factor receptor targeting affibodies to the PDT clusters, highlighting their promise as theranostic photodynamic agents.


Subject(s)
DNA, Satellite/chemistry , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Nanoparticles/chemistry , Photochemotherapy/methods , Photosensitizing Agents/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Humans , Singlet Oxygen/chemistry
10.
J Surg Oncol ; 116(4): 533-544, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28743171

ABSTRACT

BACKGROUND AND OBJECTIVES: The study aimed to investigate the relationship between obesity and postsurgical gastroparesis syndrome (PGS), and to construct a scoring system and a risk model to identify patients at high risk. METHODS: A total of 634 patients were retrospectively analyzed. Clinical characteristics were evaluated via receiver operating characteristic (ROC) curve analysis. Logistic analysis was performed to determine the independent predictive indicators of PGS. A scoring system consisting of these indicators and a risk-rating model were constructed and evaluated via ROC curve analysis. RESULTS: Based on the ROC curves, the visceral fat area (VFA) cutoff value for PGS was 94.00. Logistic analysis showed that visceral obesity (VFA ≥ 94.00 cm2 ), the reconstruction technique, and tumor size were independent prognostic factors for PGS. The scoring system could predict PGS reliably with a high area under the ROC curve ([AUC] = 0.769). A high-risk rating had a high AUC (AUC I = 0.56, AUC II = 0.65, and AUC III = 0.77), indicating that the risk-rating model could effectively screen patients at high risk of PGS. CONCLUSIONS: Visceral obesity defined by VFA effectively predicted PGS. Our scoring system may be a reliable instrument for identifying patients most at risk of PGS.


Subject(s)
Gastrectomy/adverse effects , Gastroparesis/etiology , Stomach Neoplasms/surgery , Aged , Female , Gastroparesis/diagnosis , Humans , Male , Middle Aged , Obesity, Abdominal/complications , Postoperative Complications , Retrospective Studies , Risk Assessment , Stomach Neoplasms/pathology
11.
Front Oncol ; 13: 1036458, 2023.
Article in English | MEDLINE | ID: mdl-37434983

ABSTRACT

Background: Metabolic syndrome (MetS) is associated with poor prognosis in many cancers. However, the relationship between metabolic syndrome and overall survival (OS) in patients with colorectal cancer (CRC) remains unclear. We aimed to comprehensively analyze whether MetS could affect postoperative complications and long-term survival in patients with CRC. Methods: We included patients who underwent CRC resection at our center between January 2016 and December 2018. Bias was reduced through propensity score matching analysis. Patients with CRC were divided into the MetS and non-MetS groups based on whether they had MetS. Univariate and multivariate analyses were used to identify risk factors affecting OS. Results: We included 268 patients; among them, 120 were included for further analysis after propensity score matching. There were no significant between-group differences in the clinicopathological features after matching. Compared with the non-MetS group, the MetS group had a shorter OS (P = 0.027); however, there was no significant between-group difference in postoperative complications. Multivariate analysis revealed that MetS (hazard ratio [HR] = 1.997, P = 0.042), tumor-node-metastasis stage (HR = 2.422, P = 0.003), and intestinal obstruction (HR = 2.761, P = 0.010) were independent risk factors for OS. Conclusions: MetS affects the long-term survival of patients with CRC without affecting postoperative complications.

12.
J Mater Chem B ; 10(37): 7450-7459, 2022 09 28.
Article in English | MEDLINE | ID: mdl-35894786

ABSTRACT

Mitochondria play a critical role in cell growth and metabolism. And mitochondrial dysfunction is closely related to various diseases, such as cancers, and neurodegenerative and cardiovascular diseases. Therefore, it is of vital importance to monitor mitochondrial dynamics and function. One of the most widely used methods is to use nanotechnology-mediated mitochondria targeting and imaging. It has gained increasing attention in the past few years because of the flexibility, versatility and effectiveness of nanotechnology. In the past few years, researchers have implemented various types of design and construction of the mitochondrial structure dependent nanoprobes following assorted nanotechnology pathways. This review presents an overview on the recent development of mitochondrial structure dependent target imaging probes and classifies it into two main sections: mitochondrial membrane targeting and mitochondrial microenvironment targeting. Also, the significant impact of previous research as well as the application and perspectives will be demonstrated.


Subject(s)
Mitochondria , Neoplasms , Humans , Mitochondria/metabolism , Nanotechnology/methods , Neoplasms/metabolism , Tumor Microenvironment
13.
ACS Appl Mater Interfaces ; 14(35): 39819-39829, 2022 Sep 07.
Article in English | MEDLINE | ID: mdl-36001395

ABSTRACT

Triple-negative breast cancer (TNBC) is a subtype of breast cancer, and it has aggressive and more frequent tissue metastases than other breast cancer subtypes. Because the proliferation of TNBC tumor cells does not depend on estrogen receptor (ER), progesterone receptor (PR), and Erb-B2 receptor tyrosine kinase 2 (HER2) and lacks accurate drug targets, conventional chemotherapy is challenging to be effective, and adverse reactions are severe. At present, the treatment strategy for TNBC generally depends on a combination of surgery, radiotherapy, and chemotherapy. Conventional administration methods have minimal effects on TNBC and cause severe damage to normal tissues. Therefore, it is an urgent task to develop an efficient and practical way of drug delivery and open up a new horizon of targeted therapy for TNBC. In our work, bovine serum albumin (BSA) acted as the protective film to prolong the circulation time of the tetrahedral framework nucleic acid (tFNA) delivery system and resist immune clearance in vivo. tFNA was used as a carrier loaded with DOX and AS1411 aptamers for the targeted treatment of triple-negative breast cancer. Compared with existing approaches, this optimized system exhibits stronger tumor-targeting so that tFNAs can be more concentrated around the tumor tissue, reducing DOX toxicity to other organs. This bionic delivery system exhibited effective tumor growth inhibition in the TNBC mice model, offering the clinical potential to promote the treatment of TNBC with great potential for clinical translation.


Subject(s)
Nucleic Acids , Triple Negative Breast Neoplasms , Albumins , Animals , Bionics , Humans , Mice , Nucleic Acids/therapeutic use , Triple Negative Breast Neoplasms/pathology
14.
Front Oncol ; 12: 1072127, 2022.
Article in English | MEDLINE | ID: mdl-36861109

ABSTRACT

Background: Few studies have compared the prognosis of different reconstruction methods after gastrectomy for gastric cancer (GC) patients with obesity. The aim of the present study was to compare postoperative complications and overall survival (OS) between the following reconstruction methods: Billroth I (B-I), Billroth II (B-II), and Roux-en-Y (R-Y) after gastrectomy for GC patients with visceral obesity (VO). Methods: We performed a double-institutional dataset study of 578 patients who underwent radical gastrectomy with B-I, B-II, and R-Y reconstructions between 2014 and 2016. VO was defined as a visceral fat area at the level of the umbilicus greater than 100 cm2. Propensity score-matching analysis was performed to balance the significant variables. Postoperative complications and OS were compared between the techniques. Results: VO was determined in 245 patients, of which 95, 36, and 114 underwent B-I, B-II, and R-Y reconstructions, respectively. B-II and R-Y were fused into the Non-B-I group due to the similar incidence of overall postoperative complications and OS. Therefore, 108 patients were enrolled after matching. The overall postoperative complications incidence and overall operative time in the B-I group were significantly lower than those in the non-B-I group. Further, multivariable analysis showed that B-I reconstruction was an independent protective factor for overall postoperative complications (odds ratio (OR) 0.366, P=0.017). However, no statistical difference in OS was found between the two groups (hazard ratio (HR) 0.644, P=0.216). Conclusions: B-I reconstruction was associated with decreased overall postoperative complications, rather than OS, in GC patients with VO who underwent gastrectomy.

15.
Magn Reson Imaging ; 94: 73-79, 2022 12.
Article in English | MEDLINE | ID: mdl-36116713

ABSTRACT

INTRODUCTION: Accurate noninvasive prenatal diagnosis of placenta accreta spectrum (PAS) disorder is critical for delivery management. PURPOSE: To evaluate the diagnostic ability of MRI features in predicting the PAS, invasive depth and postpartum hemorrhage (PPH) in high-risk gravid patients. MATERIALS AND METHODS: Between February 2019 and November 2020, women with ultrasound (US)-suspected PAS were enrolled. With the exclusion criteria, 80 women were included in the study. Two experienced genitourinary radiologists reviewed and recorded the MRI features. The chi square test was used to compare the effectiveness of MRI features. Relative risk ratios were computed to test the association of intraplacental T2-hypointense bands with poor outcomes of cesarean section. Receiver operating characteristic (ROC) analyses based on the number and area of intraplacental T2-hypointense bands were used to predict PAS, invasion depth, and PPH. RESULTS: PAS was diagnosed in 56 of 80 women (70%). At delivery, 24 of 80 women (30%) experienced PPH (≥1000 mL). Intraplacental T2-hypointense bands were detected at MRI in 28 of 56 women with PAS (50%). The relative risk ratio of intraplacental T2-hypointense bands was 1.51 for PAS, 3.17 for depth of PAS invasiveness and 4.74 for PPH. The largest areas of intraplacental T2-hypointense bands for predicting PAS, invasion depth and PPH were 0.66 cm2, 1.68 cm2 and 1.99 cm2, respectively. DISCUSSION: The appearance of intraplacental T2-hypointense bands has important diagnostic value for PAS, its invasion depth and PPH. The area of the largest T2-hypointense band in the placenta can predict poor outcomes of cesarean section.


Subject(s)
Placenta Accreta , Placenta Previa , Postpartum Hemorrhage , Humans , Female , Pregnancy , Placenta/diagnostic imaging , Postpartum Hemorrhage/diagnostic imaging , Cesarean Section , Placenta Accreta/diagnostic imaging , Magnetic Resonance Imaging , Retrospective Studies
16.
Curr Stem Cell Res Ther ; 16(1): 57-65, 2021.
Article in English | MEDLINE | ID: mdl-32321409

ABSTRACT

As the proportion of the elderly population increases, more and more people suffer from aging-related diseases. Even if aging is inevitable, prolonging the time of healthy aging, delaying the progression of aging-related diseases, and the incidence of morbidity can greatly alleviate the pressure on individuals and society. Current research and exploration in the field of materials related to aging are expanding tremendously. Here, we present a summary of recent research in the field of nanomaterials relevant to aging. Some nanomaterials, such as silica nanomaterials (NMs) and carbon nanotubes, cause damage to the cells similar to aging processes. Other nanomaterials such as fullerenes and metalbased nanomaterials can protect the body from endogenous and exogenous harmful substances such as ROS by virtue of their excellent reducing properties. Another new type of nucleic acid nanomaterial, tetrahedral framework nucleic acids, works effectively against cell damage. This material selectively clears existing senescent cells in the tissue and thus prevents the development of the chronic inflammatory environment caused by senescent cells secreting senescence-associated secretory phenotype to the surroundings. We believe that nanomaterials have tremendous potential to advance the understanding and treatment of aging-related disorders, and today's research only represents the beginning stages.


Subject(s)
Aging/physiology , Nanostructures/chemistry , Aging/genetics , Animals , Cellular Senescence , Epigenesis, Genetic , Genomic Instability , Humans
17.
Signal Transduct Target Ther ; 6(1): 351, 2021 10 08.
Article in English | MEDLINE | ID: mdl-34620843

ABSTRACT

DNA, a genetic material, has been employed in different scientific directions for various biological applications as driven by DNA nanotechnology in the past decades, including tissue regeneration, disease prevention, inflammation inhibition, bioimaging, biosensing, diagnosis, antitumor drug delivery, and therapeutics. With the rapid progress in DNA nanotechnology, multitudinous DNA nanomaterials have been designed with different shape and size based on the classic Watson-Crick base-pairing for molecular self-assembly. Some DNA materials could functionally change cell biological behaviors, such as cell migration, cell proliferation, cell differentiation, autophagy, and anti-inflammatory effects. Some single-stranded DNAs (ssDNAs) or RNAs with secondary structures via self-pairing, named aptamer, possess the ability of targeting, which are selected by systematic evolution of ligands by exponential enrichment (SELEX) and applied for tumor targeted diagnosis and treatment. Some DNA nanomaterials with three-dimensional (3D) nanostructures and stable structures are investigated as drug carrier systems to delivery multiple antitumor medicine or gene therapeutic agents. While the functional DNA nanostructures have promoted the development of the DNA nanotechnology with innovative designs and preparation strategies, and also proved with great potential in the biological and medical use, there is still a long way to go for the eventual application of DNA materials in real life. Here in this review, we conducted a comprehensive survey of the structural development history of various DNA nanomaterials, introduced the principles of different DNA nanomaterials, summarized their biological applications in different fields, and discussed the current challenges and further directions that could help to achieve their applications in the future.


Subject(s)
Antineoplastic Agents , DNA , Drug Delivery Systems , Nanostructures , Neoplasms/drug therapy , Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , DNA/chemistry , DNA/therapeutic use , Humans , Nanostructures/chemistry , Nanostructures/therapeutic use
18.
Front Oncol ; 11: 750768, 2021.
Article in English | MEDLINE | ID: mdl-34804939

ABSTRACT

BACKGROUND: Asians have the highest incidence of gastric cancer (GC), and the prognosis of Asian GC is poor. Furthermore, the therapeutics for Asian GC is limited because of genetic heterogeneity and screening difficulty at the early stage. This study aimed to develop an immune-related gene (IRG)-based prognostic signature and to explore prognosis-related regulatory mechanism and therapeutic target for Asian GC. METHODS: To elucidate the prognostic value of IRGs in Asian GC, a comprehensive analysis of IRG expression profiles and overall survival times in 364 Asian GC patients from the Asian Cancer Research Group (ACRG) and The Cancer Genome Atlas (TCGA) databases was performed, and a novel prognostic index was established. To further explore regulatory prognosis mechanisms and therapeutic targets, a tumor immunogenomic landscape analysis, including stromal and immune subcomponents, cell types, panimmune gene sets, and immunomodulatory genes, was performed. RESULT: Our analysis allowed the creation of an optimal risk assessment model, the Asian-specific IRG-based prognostic index (ASIRGPI), which showed a high accuracy in predicting survival in Asian GC. We also developed an ASIRGPI-based nomogram to predict the 3- and 5-year overall survival (OS) of Asian GC patients. The impact of the ASIRGPI on the worse prognosis of Asian GC was possibly related to the stromal component remodeling. Specifically, TGFß gene sets were significantly associated with the ASIRGPI and worse prognosis. Immunomodulatory gene analysis further revealed that TGFß1 and EDNRB may be the novel potential therapeutic targets for Asian GC. CONCLUSIONS: As a tumor microenvironment-relevant gene set-based prognostic signature, the ASIRGPI model provides an effective approach for evaluating the prognosis of Asian GC and may even prolong OS by enabling the selection of individualized therapy with the novel targets.

19.
Oncol Lett ; 21(5): 402, 2021 May.
Article in English | MEDLINE | ID: mdl-33777225

ABSTRACT

Recognized as a group I carcinogen for gastric cancer (GC) and a factor involved in the development of GC, Helicobacter pylori serves a major part in GC research. However, most studies have focused on H. pylori itself, ignoring the complicated pathogenic microbiological environment of GC and neglecting the synergistic or antagonistic effects of H. pylori with other pathogenic microorganisms. Increasing evidence has revealed that the human cytomegalovirus (HCMV) is present in several types of tumors and serves an important role in the neoplastic process of certain human malignant tumors, including GC. The aim of the present study was to explore the role of HCMV and H. pylori co-infection in GC. HCMV and H. pylori infection was analyzed in paired gastric tumor and peri-tumoral tissues from 134 (98 male and 36 female) patients using PCR. The results revealed that a total of 74 (55.2%) patients had H. pylori infection, 58 patients (43.3%) had HCMV infection, and 34 (25.4%) patients had both HCMV and H. pylori infection. Univariate and multivariate analyses demonstrated that H. pylori infection was independently associated with advanced lymphatic metastasis [P=0.007; odds ratio (OR)=3.51]. Furthermore, compared with HCMV-/H. pylori -, neither HCMV+/H. pylori - nor HCMV+/H. pylori + were associated with metastasis, but HCMV-/H. pylori + co-infection status was an independent risk factor for advanced lymphatic metastasis (P=0.005; OR=6.00). In conclusion, GC co-infected with HCMV and H. pylori exhibited a low tendency of lymph node metastasis. HCMV may interact with H. pylori to inhibit the process of lymphatic metastasis, and the mechanism requires further investigation.

20.
J Cancer ; 12(7): 2113-2121, 2021.
Article in English | MEDLINE | ID: mdl-33754010

ABSTRACT

Background: Laparoscopic gastrectomy for gastric cancer shortens the recovery period without decreasing long-term survival. However, clinical evidence on whether laparoscopic radical gastrectomy reduces the surgical stress and improves the short- and long-term outcomes of obese patients with gastric cancer is lacking. We compared the short- and long-term outcomes of gastric cancer patients with visceral obesity (VO) who underwent laparoscopic gastrectomy (LG) or open gastrectomy (OG). Methods: We prospectively collected data from 578 patients who underwent radical gastrectomy in two centers between January 2014 and December 2016. The visceral fat area (VFA) was measured on the umbilicus level, and VFA ≥100 cm2 was defined as VO. The section bias was reduced by conducting a propensity score matching analysis. The short- and long-term outcomes were further compared between patients who underwent OG and those who underwent LG. Results: Overall, 245 patients (42.61%) were classified as having VO, of whom 102 were included for further analysis after matching. There were no significant differences in clinical characteristics between the two groups in the matched cohort. The LG group had significantly fewer overall complications (P<0.001) and shorter postoperative hospital stays (P<0.001). Subgroup analysis of postoperative complications also showed that the incidence of surgical complications was lower in the LG group (P=0.002). Further survival analysis showed the LG group had significantly better long-term overall survival (P=0.017). Conclusions: Compared with open radical gastrectomy, laparoscopy would reduce the rate of postoperative complications in patients with VO, as well as prolong their overall survival.

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