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Objective:To establish a method for preparing ferritin-Prussian blue nanocomposites (ferritin-PB NPs) and evaluate their photothermal conversion performance and photothermally responsive tumor cell killing effect.Methods:Prussian blue nanomaterials were prepared by the precipitation method and then loaded into the ferritin cavity to construct ferritin-PB NPs. The composition of ferritin-PB NPs was tested by infrared spectroscopy and UV-vis absorption spectroscopy. The size and morphology of ferritin-PB NPs were measured by dynamic light scattering and transmission electron microscopy. The photothermal heating effect and photothermal stability effect of the ferritin-PB NPs material were tested by a thermal imager. The uptake effect of ferritin-PB NPs in HeLa and HepG2 tumor cells was observed by laser confocal microscopy. The photothermal killing effect of ferritin-PB NPs on HeLa tumor cells was tested by the MTT assay.Results:The morphology of the ferritin-PB NPs is a composite structure of ferritin coated with PB NPs, which can rapidly convert light energy into heat energy in response to 730 nm laser irradiation, resulting in a significant increase in the temperature of the test solution. The ferritin-PB NPs were rapidly taken up by HeLa and HepG2 tumor cells and significantly inhibited the proliferation of HeLa cells under 730 nm light irradiation.Conclusions:The ferritin-PB NPs were obtained by a simple preparation method, which has good biocompatibility and photothermal cytotoxicity and is expected to be used for in vivo tumor therapy in the extended research.
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Although tumor treatment models have been continuously improved in clinical practice, cancer remains a serious threat to human health. The effect of probiotics on tumor therapy has received extensive attention. As a common colonizer of the intestinal mucosa, Akkermansia muciniphila(AKK) has a well-defined role in metabolic diseases, but its complex role in tumor development and therapeutic efficacy has not been fully elucidated. The unique properties and physiological roles of AKK play an important role in different solid tumors and it may be a potential biomarker. This article provides a review of previous studies and proposes clinical strategies to influence the abundance of AKK to provide a theoretical reference for the development of next-generation probiotics and the reshaping of the tumor treatment landscape.
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Tumor microenvironment (TME) is composed of endothelial cells, pericytes, immune cells, cancer-associated fibroblasts (CAFs), cancer stem cells (CSCs), extracellular matrix (ECM) and other components of the complex biological environment. TME interacts with the tumor cells through a large amount of signaling pathways, participates in the process of tumor progression, invasion, and metastasis. Hence, TME has become a potential therapeutic target for cancer treatment, exhibiting excellent therapeutic potential and research value in the field of cancer treatment. Currently, the novel nanotechnology has been widely applied in anticancer therapy, and nanotechnology-mediated drug delivery system is being explored to apply in TME modulation to inhibit tumor progression. Nanotechnology-mediated drug delivery has many advantages over traditional therapeutic modalities, including longer circulation times, improved bioavailability, and reduced toxicity. This review summarized the research of targeted nano-drug delivery based on TME regulation, including regulation strategies based on CSCs, CAFs, immune cells, ECM, tumor vascularization, exosomes, and microbiota. In addition, we summarized the advantages, opportunities, and challenges of TME regulation strategy compared with traditional treatment strategy, which provides a reference for the application of nano-drug delivery system based on TME regulation strategy in tumor precision therapy.
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Carbonic anhydrase IX (CAIX) is a transmembrane protein that is specifically overexpressed on the surface of hypoxic tumor cells. With the function of regulating the acidity of tumor cells both inside and outside, CAIX is closely related to tumor proliferation, invasion and metastasis. Therefore, CAIX is a promising target for tumor imaging and therapy. Herein, we summarized recent advances in CAIX-based tumor imaging, therapy and theranostics, and prospected future applications of using CAIX as an anti-tumor target.
Subject(s)
Carbonic Anhydrase IX , Carbonic Anhydrases/metabolism , Cell Line, TumorABSTRACT
Hazardous environmental factors as well as occupational factors can lead to elevated incidence of diseases including tumors, and specific molecular biomarkers are needed to guide the diagnosis and treatment of diseases. In recent years, ubiquitin-specific protease 14 (USP14) has gradually attracted the attention of researchers. USP14 is widely expressed in various organs of human body and regulates the stability and degradation of important proteins in various signaling pathways. Studies have shown that its abnormal expression is highly correlated with tumors, neurodegenerative diseases, autophagy, immune response, and viral infections, and is involved in the regulation of various classic signaling pathways. It has been shown to play a key role in the development of various human diseases and can be used as a diagnostic and prognostic molecular biomarker and therapeutic target in the development of tumors. This paper reviewed the current status of research on the structure and regulation of USP14 and its function in physiological and pathological processes, with the aim of providing a reference for research on diseases or injuries caused by environmental and occupational factors.
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Pyroptosis， an atypical new cell death mode other than apoptosis and necrosis， has been discovered in recent years. Pyroptosis depends on the cleavage of gasdermins （GSDMs） by Caspases. The activated GSDMs act on the plasma membrane to form a perforation， which results in cell lysis and triggers inflammation and immune response. Pyroptosis can be induced by four distinct signaling pathways， including canonical and non-canonical inflammasome pathways， apoptosis-associated Caspases-mediated pathway， and granzyme pathway. In these signaling pathways， GSDMs are the executors of pyroptosis. Pyroptosis is associated with the death of tumor cells and the inflammatory damage of normal tissues. Recent studies have demonstrated that moderate pyroptosis can lead to tumor cell death to exert an anti-tumor effect， and meanwhile stimulate the tumor immune microenvironment， while it can promote tumor development. Despite the good performance， drug-based anti-tumor therapies such as tumor immunotherapy， chemotherapy， and targeted therapy have some shortcomings such as drug resistance， recurrence， and damage to normal tissues. The latest research shows that a variety of natural compounds have anti-tumor effects in the auxiliary treatment of tumors by mediating the pyroptosis pathways in a multi-target and multi-pathway manner， which provide new ideas for the study of anti-tumor therapy. We reviewed the molecular mechanism of pyroptosis and the regulatory role of pyroptosis in tumors and tumor immune microenvironment， and summarized the recent research progress in the natural medicinal components regulating pyroptosis in anti-tumor therapy， with a view to providing ideas for the research on the anti-tumor therapy based on pyroptosis.
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In recent years, basic scientific research and clinical studies on mesenchymal stem cell-derived exosome (MSC-Exo) have developed rapidly. MSC-Exo has shown good anti-tumor effects in preclinical and clinical studies. However, due to its diverse sources and functions, MSC-Exo therapy still faces many ethical issues in clinical conversion and application, including the unclear tumor types and mechanisms of action applicable to MSC-Exo, the risk/benefit issues in the process of clinical research, the lack of safety/effectiveness evaluation standards, lax access standards, and the incomplete regulatory systems. The technical guidelines and regulatory policies related to the clinical transformation and application of stem cell therapy are constantly improving. Therefore, to effectively avoid ethical risks, regulate the research and treatment related to the clinical transformation and application of MSC-Exo therapy, and improve the safety and efficacy of MSC-Exo therapy in tumor therapy, it is proposed to deepen clinical research on the relationship between MSC-Exo and tumor regulation, strengthen the risk/benefit analysis, supervise and improve the professional quality of researcher, deeply root in the principle of subjects not to be harmed, construct and perfect the relevant regulatory system, and improve the reviewing ability of the ethics committee, so as to promote the rapid clinical transformation of MSC-Exo and bring good news to cancer patients.
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Alternative splicing is the key to human gene expression regulation and plays a decisive role in enlarging the diversity of functional proteins. Alternative splicing is an important biomarker in tumor progression, which is closely related to the development of tumors. Tumor cells tend to produce alternative spliceosome that are conducive to their progression. Therefore, targeting regulation of tumor-specific alternative spliceosomes is a potential strategy for tumor therapy. Herein, we provide a brief review of the complex relationship between alternative splicing and tumors. Alternative splicing works by removing non-coding sequences of pre-mRNA and assembling protein-coding fragments in different combinations, ultimately producing proteins with different or even opposite functions. Alternative splicing events can promote the transformation of tumor cells through apoptosis, invasion, metastasis, angiogenesis, and metabolism; they can also influence the effectiveness of cancer immunotherapy by affecting genes that play a key role in the immune pathway. We proposed that direct or indirect targeting of alternative splicing factors and oligonucleotide-based therapies are the main strategies to reverse tumor alternative splicing events. These findings will help us to better understand tumor-related alternative splicing and to develop new strategies for tumor treatment.
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Pancreatic neuroendocrine neoplasms (pNENs) is one of the gastrointestinal malignancies of significantly heterogeneous, pathologically classified into well differentiated pancreatic neuro-endocrine tumors (pNETs) and poorly differentiated pancreatic neuroendocrine carcinomas. The prognosis and treatment response of pNETs are primely determined by tumor-intrinsic biolo-gical behavior. Accordingly, surgeons need to operate debulking surgery for low-risk patients, as well as implement adjuvant therapies for those at high-risk of relapse and metastasis after curative resection. Notably, as to two distinct subtypes of patients who suffer primary tumor with diameter less than 2 cm and functional pNETs, oncological benefits and functionally symptomatic control should be considered when formulating surgical strategies. In recent years, advances in next-generation sequencing and organoid technologies have provided practical tools for revealing the gene mutations and tumor microenvironment of pNETs. The four signalling pathways, including mTOR signalling, histone modification, altered telomere length and DNA damage repair pathways, are related to the occurrence and development of pNETs and can be used for the personalization precision therapy of pNETs and guiding the development of new drugs. Empirical therapy and clinical trial studies of pNETs are a continuum of contradictions. Therefore, clinicians need to summarize the rules in treatment and develop disciplines in the summary. Based on relevant literatures, the authors explore the hot issues related to pNENs in recent years, in order to provide reference for the diagnosis and treatment of this disease.
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With the deepening research of comprehensive treatment for gastric cancer, the FLOT regimen has begun to be used for the treatment of gastric cancer patients. FLOT neoadjuvant regimen can significantly improve the R 0 resection rate and prolong the overall survival time of locally advanced gastric cancer patients. FLOT regimen combined with immune-checkpoint inhibi-tors, targeted therapy and hyperthermic intraperitoneal chemotherapy have great potential in neo-adjuvant therapy for gastric cancer. The authors systematically analyse the development history and latest clinical research progress of FLOT neoadjuvant regimen for gastric cancer based on their clinical practice experience.
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Metal-organic frameworks (MOFs) are mixed porous materials which are composed of metal clusters or ions and organic pillars. Given their channel tunability, high porosity, large specific surface area, and good biocompatibility, MOFs can be combined with various biological macromolecules. In recent years, they have been widely studied in the field of biomedicine, especially in the loading of anti-tumor drugs, showing great application prospects. Multifunctional anti-tumor MOF combined with different therapeutic methods provides a new idea and method for tumor treatment. On the basis of the structure of MOF, this paper introduces the advantages of using MOF to load anti-tumor drugs and reviews the application of MOF in tumor therapy.
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Nanotechnology has shown broad application prospects in the diagnosis and treatment of cancer. Currently, nearly 80 cancer nanomedicines are under clinical investigation, and many have been approved with enhanced anti-tumor efficacy and decreased side effects. However, the presence of various barriers in related basic research, process control and clinical trials lead to extremely low translation rate. From the perspective of clinical commercialization, we summarized the progress, clinical status, challenges and opportunities of cancer nanomedicine, and presented a cutting-edge prospect on the rational design of nanomedicine and clinical trial strategies.
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Accurately delineating tumor boundaries is key to predicting survival rates of cancer patients and assessing response of tumor microenvironment to various therapeutic techniques such as chemotherapy and radiotherapy. This review discusses various strategies that have been deployed to accurately delineate tumor boundaries with particular emphasis on the potential of chemotherapeutic nanomaterials in tumor boundary delineation. It also compiles the types of tumors that have been successfully delineated by currently available strategies. Finally, the challenges that still abound in accurate tumor boundary delineation are presented alongside possible perspective strategies to either ameliorate or solve the problems. It is expected that the information communicated herein will form the first compendious baseline information on tumor boundary delineation with chemotherapeutic nanomaterials and provide useful insights into future possible paths to advancing current available tumor boundary delineation approaches to achieve efficacious tumor therapy.
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Mucin16 (MUC16), also known as carbohydrate antigen 125 (CA125), is a glycoprotein antigen that can be recognized by the monoclonal antibody OC125 detected from epithelial ovarian carcinoma antigen by Bast et al in 1981. CA125 is not present in normal ovarian tissue but is usually elevated in the serum of epithelial ovarian carcinoma patients. CA125 is the most commonly used serologic biomarker for the diagnosis and recurrence monitoring of epithelial ovarian carcinoma. MUC16 is highly expressed in varieties of tumors. MUC16 can interact with galectin-1/3, mesothelin, sialic acid-binding immunoglobulin-type lectins-9 (Siglec-9), and other ligands. MUC16 plays an important role in tumor genesis, proliferation, migration, invasion, and tumor immunity through various signaling pathways. Besides, therapies targeting MUC16 have some significant achievements. Related preclinical studies and clinical trials are in progress. MUC16 may be a potential novel target for tumor therapy. This article will review the mechanism of MUC16 in tumor genesis and progression, and focus on the research actuality of MUC16 in tumor therapy. This article also provides references for subsequent tumor therapy studies targeting MUC16. .
Subject(s)
Female , Humans , CA-125 Antigen/metabolism , Carcinoma, Ovarian Epithelial , Lung Neoplasms , Membrane Proteins/metabolism , Ovarian Neoplasms/pathologyABSTRACT
Liposome is an ideal drug carrier with many advantages such as excellent biocompatibility, non-immunogenicity, and easy functionalization, and has been used for the clinical treatment of many diseases including tumors. For the treatment of tumors, liposome has some passive targeting capability, but the passive targeting effect alone is very limited in improving the drug enrichment in tumor tissues, and active targeting is an effective strategy to improve the drug enrichment. Therefore, active targeting liposome drug-carriers have been extensively studied for decades. In this paper, we review the research progresses on active targeting liposome drug-carriers based on the specific binding of the carriers to the surface of tumor cells, and summarize the opportunities, challenges and future prospects in this field.
Subject(s)
Humans , Drug Carriers/therapeutic use , Drug Delivery Systems , Liposomes/therapeutic use , Neoplasms/drug therapyABSTRACT
@#Au nanoplates (Au NPLs), a kind of novel two-dimensional metal materials with nanometer scale thickness, have attracted much attention due to their excellent properties; and have been widely used in the fields of tumor diagnosis and treatment in recent years.This article introduces the characteristics and preparation methods of Au nanoplates and summarizes their application in tumor diagnosis and treatment in recent years, in order to provide reference and ideas for the research and application of Au nanoplates in tumor.
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In recent years, it has already run into a common view that "tumor is a metabolic disease", and the reprogramming of tumor metabolism has become the focus of current research. One-carbon metabolism involves folate cycle, methionine cycle and trans-sulfuration pathway. By utilizing these three ways, one carbon unit can regulate tumor growth and proliferation with the production of pyrimidine, thymidine, s-adenosine, glutathione, etc. This paper mainly describes the production and utilization of one carbon unit in tumor, as well as the interaction between one carbon metabolism and tumor development, providing new ideas for studying the mechanism of one-carbon metabolism in tumorigenesis and the treatment of nutrients in tumor.
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In recent years, neoadjuvant therapy, which can reduce the tumor stage, increase the surgical resection rate and the proportion of radical resection, reduce the risk of tumor recurrence and metastasis thus bringing survival benefit for local advanced gastric cancer patients, plays increasingly important roles in the comprehensive treatment of gastric cancer. In China, the early diagnosis rate of gastric cancer is particularly low and most patients with gastric cancer are diagnosed as locally advanced. Therefore, it is of crucial importance to discuss the current status and challenges of neoadjuvant therapy in gastric cancer. Combined with the existing clinical research results and guidelines and consensus, the authors analyze the application of neoadjuvant therapy in the comprehensive treatment of gastric cancer. Currently, more high-quality clinical trials are still needed to answer the questions related to neoadjuvant therapy of gastric cancer, such as the indication and regimen, and the optimal cycles and doses of agents, combination of targeted therapy or immunotherapy. Furthermore, how to tailor the individualized treatment strategies according to the pathological stages, molecular characteristics and gene polymophism of patients are still the problems unsolved nowadays. The authors comprehensively analyze the literature at home and abroad to deeply explore the current status and challenges of neoadjuvant therapy in gastric cancer.
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Objective:To prepare hollow copper selenide nanoparticles (Cu 2- xSe NPs), and investigate their photothermal properties and radiotherapy sensitization performance. Methods:Hollow copper selenide nanoparticles (Cu 2- xSe NPs) were prepared by sacrificial template method with Cu 2O NPs as sacrificial templates and with selenium powder as selenium source. The surface of copper selenide nanoparticles (Cu 2- xSe NPs) was modified with mercapto-ethylene glycol (mPEG-SH) to obtain Cu 2- xSe-PEG NPs. The morphology, particle size and ultraviolet spectrum of the Cu 2- xSe NPs were characterized by transmission electron microscopy, laser particle size analyzer and ultraviolet spectrophotometer. The photothermal properties and radiosensitization performance of the Cu 2- xSe-PEG NPs were investigated by infrared thermal imager and biological X-ray irradiator. Results:The obtained Cu 2- xSe NPs showed a hollow structure and good monodispersity, and the average diameter were (136.9±7.0) nm. The Cu 2- xSe NPs had absorption in the near-infrared region. When the Cu 2- xSe-PEG NPs sample with the mass concentration of 200 μg/ml were irradiated under 808 nm laser at 1.0 W/cm 2 for 10 min, the temperature raised to more than 55 ℃. The level of reactive oxygen species produced by the Cu 2- xSe-PEG NPs under X-ray irradiation was related to the concentration and radiation dose. Conclusions:The proposed preparation method can control the size of synthesized Cu 2- xSe NPs, and the Cu 2- xSe NPs had good photothermal properties and radiosensitization performance. This work will provide a certain theoretical basis for the application of Cu 2- xSe-PEG NPs in tumor thermoradiotherapy.
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@#Poly-adenosine diphosphate ribose polymerases (PARPs) play an important role in DNA repair and apoptosis.Among them, mono-(ADP-ribosyl) transferase (MARTs) can regulate various cell reactions by catalyzing and transferring single ADP-ribose.Most MARTs are highly expressed in cancers, which is closely related to the occurrence and progression of cancers.This review introduces the MARTs that are highly expressed in cancers, classifies them according to the differences of their structural domains, and reviews their known mechanism, their close relationship with cancers, their potential value in cancer therapy and the research progress of corresponding inhibitors.These targets are expected to provide new research ideas for cancer therapy in the era of precision medicine.