Purpose: To establish a HPLC testing method of the content of bulk picoplatin and its impurities. Method: the separation was perform on a C18 column(4.6 mm×250 mm, 5 m) with potassium dihydrogen phosphate-aceton-...Purpose: To establish a HPLC testing method of the content of bulk picoplatin and its impurities. Method: the separation was perform on a C18 column(4.6 mm×250 mm, 5 m) with potassium dihydrogen phosphate-aceton-itrile as the mobile phase at a flow rate of 1.0 mL/min. The detecting wavelength was set at 210 nm, and the column temperature was set at 30℃. Result: in the method validation, the linear relationship modulus of picoplatin is 0.9999, the systemic precision is 0.44%, the method precision is 0.74%, the average recovery rate is 99.62%, the LOD and LOQ of picoplatin is 0.2 ng and 1.0 ng. The average resolution of picoplatin and its impurities is more than 2. Conclusion: The established method is good specificity, high sensitivity, and good repeatability which could provide scientific evidence for the quality control of picoplatin and its impurities.展开更多
In order to control the silver content in the preparation process of platinum group anti-cancer drugs, we put two kinds of color reagent to color in the production process of the platinum anti-cancer drugs by UV spect...In order to control the silver content in the preparation process of platinum group anti-cancer drugs, we put two kinds of color reagent to color in the production process of the platinum anti-cancer drugs by UV spectra measurement to control drugs production of platinum anticancer, thus we could control the silver content in the drugs so that it meets the pharmacopoeia standards of US and展开更多
RP215 is one of the three thousand monoclonal antibodies (Mabs) which were generated against the OC-3-VGH ovarian cancer cell line. RP215 was shown to react with a carbohydrate-associated epitope located specifically ...RP215 is one of the three thousand monoclonal antibodies (Mabs) which were generated against the OC-3-VGH ovarian cancer cell line. RP215 was shown to react with a carbohydrate-associated epitope located specifically on glycoproteins, known as CA215, from cancer cells. Further molecular analysis by matrix adsorption laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) revealed that CA215 consists mainly of immunoglobulin super-family (IgSF) proteins, including immunoglobulins, T-cell receptors, and cell adhesion molecules, as well as several other unrelated proteins. Peptide mappings and glycoanalysis were performed with CA215 and revealed high-mannose and complex bisecting structures with terminal sialic acid in N-glycans. As many as ten O-glycans, which are structurally similar to those of mucins, were also identified. In addition, two additional O-linked glycans were exclusively detected in cancerous immunoglobulins but not in normal B cell-derived immunoglobulins. Immunizations of mice with purified CA215 resulted in the predominant generation of RP215-related Mabs, indicating the immunodominance of this carbohydrate-associated epitope. Anti-idiotype (anti-id) Mabs of RP215, which were generated in the rat, were shown to contain the internal images of the carbohydrate-associated epitope. Following immunizations of these anti-id Mabs in mice, the resulting anti-anti-id (Ab3) responses in mice were found to be immunologically similar to that of RP215. Judging from these observations, anti-id Mabs, which carry the internal image of the RP215-specific epitope, may be suitable candidates for anticancer vaccine development in humans.展开更多
Cancer-beating molecules (CBMs) are abundant in many types of food and potentially anti-cancer therapeutic agents. In the previous work, researchers introduced a network-based machine learning platform to identify the...Cancer-beating molecules (CBMs) are abundant in many types of food and potentially anti-cancer therapeutic agents. In the previous work, researchers introduced a network-based machine learning platform to identify the cancer-beating molecules, for example,?comparing the similarities in the molecular network between approved anticancer drug and food molecules. Herein, we aim to build on this work to enhance the accuracy of predicting food molecules. In this project, we improve supervised learning approaches by applying Soft Voting algorithm to seven machine learning algorithms: Support Vector Machine with Radial Basis Function (SVM with RBF kernel), multilayer perceptron neural network?(MLP), Random forest, Decision trees,?Gaussian Naive Bayes, Adaboosting, and Bagging. As a result, the accuracy in the dataset of 50 food molecules utilized increased from 82% to 87%, achieving a significant improvement in the precision of?predicting anti-cancer molecules.展开更多
Cancer constitutes a heterogenic cellular system with a high level of spatio-temporal complexity.Recent discoveries by systems biologists have provided emerging evidence that cellular responses to anti-cancer modaliti...Cancer constitutes a heterogenic cellular system with a high level of spatio-temporal complexity.Recent discoveries by systems biologists have provided emerging evidence that cellular responses to anti-cancer modalities are stochastic in nature.To uncover the intricacies of cell-to-cell variability and its relevance to cancer therapy,new analytical screening technologies are needed.The last decade has brought forth spectacular innovations in the field of cytometry and single cell cytomics,opening new avenues for systems oncology and high-throughput real-time drug screening routines.The up-and-coming microfluidic Lab-on-a-Chip(LOC)technology and micrototal analysis systems(μTAS)are arguably the most promising platforms to address the inherent complexity of cellular systems with massive experimental parallelization and 4D analysis on a single cell level.The vast miniaturization of LOC systems and multiplexing enables innovative strategies to reduce drug screening expenditures while increasing throughput and content of information from a given sample.Small cell numbers and operational reagent volumes are sufficient for microfluidic analyzers and,as such,they enable next generation high-throughput and high-content screening of anticancer drugs on patient-derived specimens.Herein we highlight the selected advancements in this emerging field of bioengineering,and provide a snapshot of developments with relevance to anti-cancer drug screening routines.展开更多
A new approach for producing polymer nanoparticles made of bovine serum albumin-poly(methy methacrylate) conjugate by precipitating in supercritical CO2 is reported. The nanoparticles were loaded with the anti-tumor d...A new approach for producing polymer nanoparticles made of bovine serum albumin-poly(methy methacrylate) conjugate by precipitating in supercritical CO2 is reported. The nanoparticles were loaded with the anti-tumor drug camptothecin. With albumin serving as a nutrient to cells, the drug-encapsulated nanoparticle shows an enhanced ability to kill cancer cells compared to that of the free drug in solution both in vitro and in vivo.展开更多
The rivalry between T cells and tumor cells somewhat mimics the scene of 'Tom and Jerry,' an animated series in which Tom (a house cat) rarely succeeds in catching Jerry (a mouse), mainly because of Jerry’s c...The rivalry between T cells and tumor cells somewhat mimics the scene of 'Tom and Jerry,' an animated series in which Tom (a house cat) rarely succeeds in catching Jerry (a mouse), mainly because of Jerry’s cleverness and cunning abilities. In a way, tumor cells are like Jerry, in terms of their crafty and sneaky features.展开更多
In the last few decades numbers of review and research articles have been published on niosomes. This shows the relevant interest of academias & researchers in niosomes because of the advantages sponsored by them ...In the last few decades numbers of review and research articles have been published on niosomes. This shows the relevant interest of academias & researchers in niosomes because of the advantages sponsored by them over other colloidal drug delivery systems. Niosomes formation occurs when non-ionic surfactant vesicles assemble themselves. Various antineoplastic agents are used in chemotherapy, but they have some drawbacks that these agents cause cell death in normal tissues as well. There are two approaches to overcome this limitation. First, to modify the structure of existing drugs, but this will not possible because it changes the properties of drugs. Second, the development of nano-carriers like liposomes, dendrimers, nanoparticles, niosomes et al. Among all, niosomes (non-ionic surfactant vesicles) have more advantages besides all nano-carriers. Drugs either hydrophilic in nature or hydrophobic in nature, both can be incorporated in niosomes. And by embedding specific ligands over vesicular surface enables us to target the drug to specific cancer cells.展开更多
Sterile α motif and histidine/aspartic acid domain containing protein 1 (SAMHD1) is a deoxynucleoside triphosphate (dNTPs) triphosphohydrolase that can hydrolyze dNTPs into deoxynucleosides and triphosphates to keep ...Sterile α motif and histidine/aspartic acid domain containing protein 1 (SAMHD1) is a deoxynucleoside triphosphate (dNTPs) triphosphohydrolase that can hydrolyze dNTPs into deoxynucleosides and triphosphates to keep the balance of the intracellular dNTPs pool. Moreover, it has been reported that SAMHD1 plays a role in regulating cell proliferation and the cell cycle, maintaining genome stability and inhibiting innate immune responses. SAMHD1 activity is regulated by phosphorylation, oxidation, SUMOylation, and O-GlcNAcylation. SAMHD1 mutations have been reported to cause diseases, including chronic lymphocytic leukemia and mantle cell lymphoma. SAMHD1 expression in acute myeloid leukemia predicts inferior prognosis. Recently, it has been revealed that SAMHD1 mediates the resistance to anti-cancer drugs. This review will focus on SAMHD1 function and regulation, the association between SAMHD1 and hematological malignancies and will provide updated information on SAMHD1 mediating resistance to nucleoside analogue antimetabolites, topoisomerase inhibitors, platinum-derived agents and DNA hypomethylating agents. Furthermore, histone deacetylase inhibitors and tyrosine kinase inhibitors indirectly increase anti-cancer drug resistance by increasing SAMDH1 activity. We herein highlight the importance of the development of novel agents targeting SAMHD1 to overcome treatment resistance of hematological malignancies, which would be an opportunity to improve the outcome of patients with refractory hematological malignancies.展开更多
Cancer stands as one of the major threats to human life.Ensuring the safety of drugs is paramount,and the impact of adverse reactions on patients’quality of life and prognosis should not be underestimated.Diarrhea is...Cancer stands as one of the major threats to human life.Ensuring the safety of drugs is paramount,and the impact of adverse reactions on patients’quality of life and prognosis should not be underestimated.Diarrhea is a common clinical adverse event,and despite the absence of specific anti-diarrhea drugs,there is a pressing need for improvement.This article aims to provide a valuable reference for researchers in clinical drug use and scientific tumor treatment.It summarizes recent advancements in drug mechanisms and adverse reactions,whether in preclinical research or clinical diagnosis and therapy.展开更多
In a recent study published in Nature Cancer,Shi et al.reported the identification of the small molecule YC-1 as the selective drug against primary liver tumor cells due to the specific expression of sulfotransferase ...In a recent study published in Nature Cancer,Shi et al.reported the identification of the small molecule YC-1 as the selective drug against primary liver tumor cells due to the specific expression of sulfotransferase family 1A member 1(SULT1A1)in hepatocytelineage cells.1 This study offered new insights into repurposing an old anti-cancer drug via harnessing hepatocyte-specific metabolic enzymes to treat primary liver tumors.展开更多
Prediction of the response of cancer patients to different treatments and identification of biomarkers of drug response are two major goals of individualized medicine.Here,we developed a deep learning framework called...Prediction of the response of cancer patients to different treatments and identification of biomarkers of drug response are two major goals of individualized medicine.Here,we developed a deep learning framework called TINDL,completely trained on preclinical cancer cell lines(CCLs),to predict the response of cancer patients to different treatments.TINDL utilizes a tissue-informed normalization to account for the tissue type and cancer type of the tumors and to reduce the statistical discrepancies between CCLs and patient tumors.Moreover,by making the deep learning black box interpretable,this model identifies a small set of genes whose expression levels are predictive of drug response in the trained model,enabling identification of biomarkers of drug response.Using data from two large databases of CCLs and cancer tumors,we showed that this model can distinguish between sensitive and resistant tumors for 10(out of 14)drugs,outperforming various other machine learning models.In addition,our small interfering RNA(siRNA)knockdown experiments on 10 genes identified by this model for one of the drugs(tamoxifen)confirmed that tamoxifen sensitivity is substantially influenced by all of these genes in MCF7 cells,and seven of these genes in T47D cells.Furthermore,genes implicated for multiple drugs pointed to shared mechanism of action among drugs and suggested several important signaling pathways.In summary,this study provides a powerful deep learning framework for prediction of drug response and identification of biomarkers of drug response in cancer.The code can be accessed at https://github.com/ddhostallero/tindl.展开更多
N6-Methyladenosine(m6 A) modification is the most pervasive modification of human mRNA molecules. It is reversible via regulation of m6 A modification methyltransferase, demethylase and proteins that preferentially re...N6-Methyladenosine(m6 A) modification is the most pervasive modification of human mRNA molecules. It is reversible via regulation of m6 A modification methyltransferase, demethylase and proteins that preferentially recognize m6 A modification as "writers", "erasers" and "readers", respectively. Altered expression levels of the m6 A modification key regulators substantially affect their function, leading to significant phenotype changes in the cell and organism. Recent studies have proved that the m6 A modification plays significant roles in regulation of metabolism, stem cell self-renewal, and metastasis in a variety of human cancers. In this review, we describe the potential roles of m6 A modification in human cancers and summarize their underlying molecular mechanisms. Moreover, we will highlight potential therapeutic approaches by targeting the key m6 A modification regulators for cancer drug development.& 2018 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).展开更多
Tauopathies,diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of fro ntotemporal dementia,make up the vast majority of dementia cases.Although there have been...Tauopathies,diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of fro ntotemporal dementia,make up the vast majority of dementia cases.Although there have been recent developments in tauopathy biomarkers and disease-modifying treatments,ongoing progress is required to ensure these are effective,economical,and accessible for the globally ageing population.As such,continued identification of new potential drug targets and biomarkers is critical."Big data"studies,such as proteomics,can generate information on thousands of possible new targets for dementia diagnostics and therapeutics,but currently remain underutilized due to the lack of a clear process by which targets are selected for future drug development.In this review,we discuss current tauopathy biomarkers and therapeutics,and highlight areas in need of improvement,particularly when addressing the needs of frail,comorbid and cognitively impaired populations.We highlight biomarkers which have been developed from proteomic data,and outline possible future directions in this field.We propose new criteria by which potential targets in proteomics studies can be objectively ranked as favorable for drug development,and demonstrate its application to our group's recent tau interactome dataset as an example.展开更多
Pterostilbene is a natural compound that can be found in various food plants such as blueberries,grapes,and peanuts.It has also been reported to be extracted from Pterocarpus indicus,a tree species native to India and...Pterostilbene is a natural compound that can be found in various food plants such as blueberries,grapes,and peanuts.It has also been reported to be extracted from Pterocarpus indicus,a tree species native to India and Southeast Asia.Pterostilbene exhibits various pharmacological activities such as antioxidants,anti-proliferation,anti-microbial,and anti-inflammatory activities with favorable pharmacokinetic properties,such as high oral bioavailability and longer half-life.The anti-inflammatory effect of pterostilbene has been reported to contribute to its therapeutic effects in many chronic inflammatory diseases.Besides,pterostilbene has anti-cancer activity on various types of cancers due to its ability to induce cell cycle arrest and apoptosis.Hence,in this review,we discuss the anti-inflammatory and anti-cancer activities of pterostilbene in preclinical studies.展开更多
Nano-drug delivery systems(nanoDDS)have been extensively investigated clinically to improve the therapeutic effect of anticancer drugs.However,the complicated synthesis during the preparation as well as the potential ...Nano-drug delivery systems(nanoDDS)have been extensively investigated clinically to improve the therapeutic effect of anticancer drugs.However,the complicated synthesis during the preparation as well as the potential drug leakage during transportation has greatly limited their general application.In this work,a calixarene-integrated nanoDDS(CanD)that achieves tumor-targeted delivery and tracking of anti-cancer drugs in vivo is presented.The hypoxia-responsive calixarene(SAC4A)exhibits high binding affinity to a series of anti-cancer drugs and rhodamine B(RhB)under normoxic condition while decreasing the binding affinity under hypoxic condition,which leads to the drug release and fluorescence recovery simultaneously.Furthermore,the hypoxia-responsiveness of SAC4A conveys CanD with tumor-targeting ability,resulting in the enrichment of the drug in tumors and enhancement in tumor suppression in mice.Moreover,CanD could become a general platform allowing the delivery of a wide scope of anti-cancer drugs that have strong host-guest interaction with SAC4A.展开更多
Due to the nontoxicity and efficient anti-cancer activity, more and more attention has been paid to N-glycoside compounds. Laser photolysis of N-(α-D-glucopyranoside) salicyloyl hydrazine (NGSH) has been performed fo...Due to the nontoxicity and efficient anti-cancer activity, more and more attention has been paid to N-glycoside compounds. Laser photolysis of N-(α-D-glucopyranoside) salicyloyl hydrazine (NGSH) has been performed for the first time. The research results show that NGSH has high photosensitivity and is vulnerable to be photo-ionized via a monophotonic process with a quantum yield of 0.02, generating NGSH+· and hydrated electrons. Under the aerobic condition of cells, the hydrated electrons are very easy to combine with oxygen to generate 1O2 and O2-, both of which are powerful oxidants that can kill the cancer cells. In addition, NGSH+· can be changed into neutral radicals by deprotonation with a pKa value of 4.02 and its decay constant was determined to be 2.55×109dm3·mol-1·s-1. NGSH also can be oxidized by SO4-. with a rate constant of 1.76×109 dm3·mol-1.s-1, which further confirms the results of photoionization. All of these results suggest that this new N-glycoside compound might be useful for cancer treatment.展开更多
Taraxasterol(TS)is a naturally occurring pentacyclic triterpenoid extracted from the traditional Chinese herb Taraxacum mongolicum.Previous studies have highlighted its significant roles in exhibiting anti-inflammator...Taraxasterol(TS)is a naturally occurring pentacyclic triterpenoid extracted from the traditional Chinese herb Taraxacum mongolicum.Previous studies have highlighted its significant roles in exhibiting anti-inflammatory,anti-oxidant,and liver protective effects.In the present study,the anti-cancer potential of TS against cervical cancer was investigated,employing network pharmacology techniques,molecular docking,and in vitro experimental validation.TS exhibits its anticancer properties by modulating multiple targets,pathways,and biological processes.In vitro experiments demonstrated the potent inhibitory effects of TS on cancer cell growth and migration,while no significant impact on apoptosis was observed.The primary objective was to elucidate the anti-cancer potential of TS,which is a crucial lead compound in the treatment of cervical cancer.The findings may serve as a basis for the development of novel anticancer therapeutics and medicine-based interventions for cervical cancer.展开更多
BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis...BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis(HT).While single symptomatic drug treatment of the two diseases is less effective,combined drug treatment may improve efficacy.AIM To investigate the effect of a combination of vitamin D,selenium,and hypoglycemic agents in T2DM with HT.METHODS This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023.Fifty patients were assigned to the control group,test group A,and test group B according to different treatment methods.The control group received low-iodine diet guidance and hypoglycemic drug treatment.Test group A received the control treatment plus vitamin D treatment.Test group B received the group A treatment plus selenium.Blood levels of markers of thyroid function[free T3(FT3),thyroid stimulating hormone(TSH),free T4(FT4)],autoantibodies[thyroid peroxidase antibody(TPOAB)and thyroid globulin antibody(TGAB)],blood lipid index[low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triacylglycerol(TG)],blood glucose index[fasting blood glucose(FBG),and hemoglobin A1c(HbA1c)]were measured pre-treatment and 3 and 6 months after treatment.The relationships between serum 25-hydroxyvitamin D3[25(OH)D3]level and each of these indices were analyzed.RESULTS The levels of 25(OH)D3,FT3,FT4,and LDL-C increased in the order of the control group,test group A,and test group B(all P<0.05).The TPOAB,TGAB,TC,TG,FBG,HbA1c,and TSH levels increased in the order of test groups B,A,and the control group(all P<0.05).All the above indices were compared after 3 and 6 months of treatment.Pre-treatment,there was no divergence in serum 25(OH)D3 level,thyroid function-related indexes,autoantibodies level,blood glucose,and blood lipid index between the control group,test groups A and B(all P>0.05).The 25(OH)D3 levels in test groups A and B were negatively correlated with FT4 and TGAB(all P<0.05).CONCLUSION The combination drug treatment for T2DM with HT significantly improved thyroid function,autoantibody,and blood glucose and lipid levels.展开更多
Veterinary drugs are substances(including pharmaceutical feed additives)used to prevent,treat,and diagnose diseases or regulate the physiological functions of animals.Veterinary drug poisoning in humans is relatively ...Veterinary drugs are substances(including pharmaceutical feed additives)used to prevent,treat,and diagnose diseases or regulate the physiological functions of animals.Veterinary drug poisoning in humans is relatively rare both in China and the rest of the world.Here,we report a case of death from veterinary drug poisoning from avermectin-closantel.Avermectin-closantel is a broad-spectrum antiparasitic drug,which has high efficacy against a variety of trematodes and nematodes.展开更多
文摘Purpose: To establish a HPLC testing method of the content of bulk picoplatin and its impurities. Method: the separation was perform on a C18 column(4.6 mm×250 mm, 5 m) with potassium dihydrogen phosphate-aceton-itrile as the mobile phase at a flow rate of 1.0 mL/min. The detecting wavelength was set at 210 nm, and the column temperature was set at 30℃. Result: in the method validation, the linear relationship modulus of picoplatin is 0.9999, the systemic precision is 0.44%, the method precision is 0.74%, the average recovery rate is 99.62%, the LOD and LOQ of picoplatin is 0.2 ng and 1.0 ng. The average resolution of picoplatin and its impurities is more than 2. Conclusion: The established method is good specificity, high sensitivity, and good repeatability which could provide scientific evidence for the quality control of picoplatin and its impurities.
文摘In order to control the silver content in the preparation process of platinum group anti-cancer drugs, we put two kinds of color reagent to color in the production process of the platinum anti-cancer drugs by UV spectra measurement to control drugs production of platinum anticancer, thus we could control the silver content in the drugs so that it meets the pharmacopoeia standards of US and
文摘RP215 is one of the three thousand monoclonal antibodies (Mabs) which were generated against the OC-3-VGH ovarian cancer cell line. RP215 was shown to react with a carbohydrate-associated epitope located specifically on glycoproteins, known as CA215, from cancer cells. Further molecular analysis by matrix adsorption laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) revealed that CA215 consists mainly of immunoglobulin super-family (IgSF) proteins, including immunoglobulins, T-cell receptors, and cell adhesion molecules, as well as several other unrelated proteins. Peptide mappings and glycoanalysis were performed with CA215 and revealed high-mannose and complex bisecting structures with terminal sialic acid in N-glycans. As many as ten O-glycans, which are structurally similar to those of mucins, were also identified. In addition, two additional O-linked glycans were exclusively detected in cancerous immunoglobulins but not in normal B cell-derived immunoglobulins. Immunizations of mice with purified CA215 resulted in the predominant generation of RP215-related Mabs, indicating the immunodominance of this carbohydrate-associated epitope. Anti-idiotype (anti-id) Mabs of RP215, which were generated in the rat, were shown to contain the internal images of the carbohydrate-associated epitope. Following immunizations of these anti-id Mabs in mice, the resulting anti-anti-id (Ab3) responses in mice were found to be immunologically similar to that of RP215. Judging from these observations, anti-id Mabs, which carry the internal image of the RP215-specific epitope, may be suitable candidates for anticancer vaccine development in humans.
文摘Cancer-beating molecules (CBMs) are abundant in many types of food and potentially anti-cancer therapeutic agents. In the previous work, researchers introduced a network-based machine learning platform to identify the cancer-beating molecules, for example,?comparing the similarities in the molecular network between approved anticancer drug and food molecules. Herein, we aim to build on this work to enhance the accuracy of predicting food molecules. In this project, we improve supervised learning approaches by applying Soft Voting algorithm to seven machine learning algorithms: Support Vector Machine with Radial Basis Function (SVM with RBF kernel), multilayer perceptron neural network?(MLP), Random forest, Decision trees,?Gaussian Naive Bayes, Adaboosting, and Bagging. As a result, the accuracy in the dataset of 50 food molecules utilized increased from 82% to 87%, achieving a significant improvement in the precision of?predicting anti-cancer molecules.
文摘Cancer constitutes a heterogenic cellular system with a high level of spatio-temporal complexity.Recent discoveries by systems biologists have provided emerging evidence that cellular responses to anti-cancer modalities are stochastic in nature.To uncover the intricacies of cell-to-cell variability and its relevance to cancer therapy,new analytical screening technologies are needed.The last decade has brought forth spectacular innovations in the field of cytometry and single cell cytomics,opening new avenues for systems oncology and high-throughput real-time drug screening routines.The up-and-coming microfluidic Lab-on-a-Chip(LOC)technology and micrototal analysis systems(μTAS)are arguably the most promising platforms to address the inherent complexity of cellular systems with massive experimental parallelization and 4D analysis on a single cell level.The vast miniaturization of LOC systems and multiplexing enables innovative strategies to reduce drug screening expenditures while increasing throughput and content of information from a given sample.Small cell numbers and operational reagent volumes are sufficient for microfluidic analyzers and,as such,they enable next generation high-throughput and high-content screening of anticancer drugs on patient-derived specimens.Herein we highlight the selected advancements in this emerging field of bioengineering,and provide a snapshot of developments with relevance to anti-cancer drug screening routines.
文摘A new approach for producing polymer nanoparticles made of bovine serum albumin-poly(methy methacrylate) conjugate by precipitating in supercritical CO2 is reported. The nanoparticles were loaded with the anti-tumor drug camptothecin. With albumin serving as a nutrient to cells, the drug-encapsulated nanoparticle shows an enhanced ability to kill cancer cells compared to that of the free drug in solution both in vitro and in vivo.
文摘The rivalry between T cells and tumor cells somewhat mimics the scene of 'Tom and Jerry,' an animated series in which Tom (a house cat) rarely succeeds in catching Jerry (a mouse), mainly because of Jerry’s cleverness and cunning abilities. In a way, tumor cells are like Jerry, in terms of their crafty and sneaky features.
文摘In the last few decades numbers of review and research articles have been published on niosomes. This shows the relevant interest of academias & researchers in niosomes because of the advantages sponsored by them over other colloidal drug delivery systems. Niosomes formation occurs when non-ionic surfactant vesicles assemble themselves. Various antineoplastic agents are used in chemotherapy, but they have some drawbacks that these agents cause cell death in normal tissues as well. There are two approaches to overcome this limitation. First, to modify the structure of existing drugs, but this will not possible because it changes the properties of drugs. Second, the development of nano-carriers like liposomes, dendrimers, nanoparticles, niosomes et al. Among all, niosomes (non-ionic surfactant vesicles) have more advantages besides all nano-carriers. Drugs either hydrophilic in nature or hydrophobic in nature, both can be incorporated in niosomes. And by embedding specific ligands over vesicular surface enables us to target the drug to specific cancer cells.
基金supported by the funding of National Natural Science Foundation of China (No. 81770209).
文摘Sterile α motif and histidine/aspartic acid domain containing protein 1 (SAMHD1) is a deoxynucleoside triphosphate (dNTPs) triphosphohydrolase that can hydrolyze dNTPs into deoxynucleosides and triphosphates to keep the balance of the intracellular dNTPs pool. Moreover, it has been reported that SAMHD1 plays a role in regulating cell proliferation and the cell cycle, maintaining genome stability and inhibiting innate immune responses. SAMHD1 activity is regulated by phosphorylation, oxidation, SUMOylation, and O-GlcNAcylation. SAMHD1 mutations have been reported to cause diseases, including chronic lymphocytic leukemia and mantle cell lymphoma. SAMHD1 expression in acute myeloid leukemia predicts inferior prognosis. Recently, it has been revealed that SAMHD1 mediates the resistance to anti-cancer drugs. This review will focus on SAMHD1 function and regulation, the association between SAMHD1 and hematological malignancies and will provide updated information on SAMHD1 mediating resistance to nucleoside analogue antimetabolites, topoisomerase inhibitors, platinum-derived agents and DNA hypomethylating agents. Furthermore, histone deacetylase inhibitors and tyrosine kinase inhibitors indirectly increase anti-cancer drug resistance by increasing SAMDH1 activity. We herein highlight the importance of the development of novel agents targeting SAMHD1 to overcome treatment resistance of hematological malignancies, which would be an opportunity to improve the outcome of patients with refractory hematological malignancies.
文摘Cancer stands as one of the major threats to human life.Ensuring the safety of drugs is paramount,and the impact of adverse reactions on patients’quality of life and prognosis should not be underestimated.Diarrhea is a common clinical adverse event,and despite the absence of specific anti-diarrhea drugs,there is a pressing need for improvement.This article aims to provide a valuable reference for researchers in clinical drug use and scientific tumor treatment.It summarizes recent advancements in drug mechanisms and adverse reactions,whether in preclinical research or clinical diagnosis and therapy.
文摘In a recent study published in Nature Cancer,Shi et al.reported the identification of the small molecule YC-1 as the selective drug against primary liver tumor cells due to the specific expression of sulfotransferase family 1A member 1(SULT1A1)in hepatocytelineage cells.1 This study offered new insights into repurposing an old anti-cancer drug via harnessing hepatocyte-specific metabolic enzymes to treat primary liver tumors.
基金supported by the New Frontiers in Research Fund(NFRF)of Government of Canada(Grant No.NFRFE-2019-01290 to Amin Emad and Junmei Cairns)the Natural Sciences and Engineering Research Council of Canada(NSERC)(Grant No.RGPIN-2019-04460 to Amin Emad)the McGill Initiative in Computational Medicine(MiCM)to Amin Emad.
文摘Prediction of the response of cancer patients to different treatments and identification of biomarkers of drug response are two major goals of individualized medicine.Here,we developed a deep learning framework called TINDL,completely trained on preclinical cancer cell lines(CCLs),to predict the response of cancer patients to different treatments.TINDL utilizes a tissue-informed normalization to account for the tissue type and cancer type of the tumors and to reduce the statistical discrepancies between CCLs and patient tumors.Moreover,by making the deep learning black box interpretable,this model identifies a small set of genes whose expression levels are predictive of drug response in the trained model,enabling identification of biomarkers of drug response.Using data from two large databases of CCLs and cancer tumors,we showed that this model can distinguish between sensitive and resistant tumors for 10(out of 14)drugs,outperforming various other machine learning models.In addition,our small interfering RNA(siRNA)knockdown experiments on 10 genes identified by this model for one of the drugs(tamoxifen)confirmed that tamoxifen sensitivity is substantially influenced by all of these genes in MCF7 cells,and seven of these genes in T47D cells.Furthermore,genes implicated for multiple drugs pointed to shared mechanism of action among drugs and suggested several important signaling pathways.In summary,this study provides a powerful deep learning framework for prediction of drug response and identification of biomarkers of drug response in cancer.The code can be accessed at https://github.com/ddhostallero/tindl.
基金supported in part by a grant from the National Natural Science Foundation of China (No. 31701114)the Fundamental Research Funds for University-Key Cultivation Project of Young Teacher in Sun Yat-Sen University (No. 17ykzd11)
文摘N6-Methyladenosine(m6 A) modification is the most pervasive modification of human mRNA molecules. It is reversible via regulation of m6 A modification methyltransferase, demethylase and proteins that preferentially recognize m6 A modification as "writers", "erasers" and "readers", respectively. Altered expression levels of the m6 A modification key regulators substantially affect their function, leading to significant phenotype changes in the cell and organism. Recent studies have proved that the m6 A modification plays significant roles in regulation of metabolism, stem cell self-renewal, and metastasis in a variety of human cancers. In this review, we describe the potential roles of m6 A modification in human cancers and summarize their underlying molecular mechanisms. Moreover, we will highlight potential therapeutic approaches by targeting the key m6 A modification regulators for cancer drug development.& 2018 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).
基金supported by funding from the Bluesand Foundation,Alzheimer's Association(AARG-21-852072 and Bias Frangione Early Career Achievement Award)to EDan Australian Government Research Training Program scholarship and the University of Sydney's Brain and Mind Centre fellowship to AH。
文摘Tauopathies,diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of fro ntotemporal dementia,make up the vast majority of dementia cases.Although there have been recent developments in tauopathy biomarkers and disease-modifying treatments,ongoing progress is required to ensure these are effective,economical,and accessible for the globally ageing population.As such,continued identification of new potential drug targets and biomarkers is critical."Big data"studies,such as proteomics,can generate information on thousands of possible new targets for dementia diagnostics and therapeutics,but currently remain underutilized due to the lack of a clear process by which targets are selected for future drug development.In this review,we discuss current tauopathy biomarkers and therapeutics,and highlight areas in need of improvement,particularly when addressing the needs of frail,comorbid and cognitively impaired populations.We highlight biomarkers which have been developed from proteomic data,and outline possible future directions in this field.We propose new criteria by which potential targets in proteomics studies can be objectively ranked as favorable for drug development,and demonstrate its application to our group's recent tau interactome dataset as an example.
基金the Ministry of Higher Education(MOHE)Malaysia through the Fundamental Research Grant Scheme(FRGS)with grant number:FRGS/1/2019/SKK10/UKM/01/1.
文摘Pterostilbene is a natural compound that can be found in various food plants such as blueberries,grapes,and peanuts.It has also been reported to be extracted from Pterocarpus indicus,a tree species native to India and Southeast Asia.Pterostilbene exhibits various pharmacological activities such as antioxidants,anti-proliferation,anti-microbial,and anti-inflammatory activities with favorable pharmacokinetic properties,such as high oral bioavailability and longer half-life.The anti-inflammatory effect of pterostilbene has been reported to contribute to its therapeutic effects in many chronic inflammatory diseases.Besides,pterostilbene has anti-cancer activity on various types of cancers due to its ability to induce cell cycle arrest and apoptosis.Hence,in this review,we discuss the anti-inflammatory and anti-cancer activities of pterostilbene in preclinical studies.
基金National Key Research and Development Programs of China(No.2018YFA0209700)National Natural Science Foundation of China(NSFC,No.22077073)+1 种基金Frontiers Science Center for New Organic Matter(No.63181206)Fundamental Research Funds for the Central Universities(Nankai University,No.63206015).
文摘Nano-drug delivery systems(nanoDDS)have been extensively investigated clinically to improve the therapeutic effect of anticancer drugs.However,the complicated synthesis during the preparation as well as the potential drug leakage during transportation has greatly limited their general application.In this work,a calixarene-integrated nanoDDS(CanD)that achieves tumor-targeted delivery and tracking of anti-cancer drugs in vivo is presented.The hypoxia-responsive calixarene(SAC4A)exhibits high binding affinity to a series of anti-cancer drugs and rhodamine B(RhB)under normoxic condition while decreasing the binding affinity under hypoxic condition,which leads to the drug release and fluorescence recovery simultaneously.Furthermore,the hypoxia-responsiveness of SAC4A conveys CanD with tumor-targeting ability,resulting in the enrichment of the drug in tumors and enhancement in tumor suppression in mice.Moreover,CanD could become a general platform allowing the delivery of a wide scope of anti-cancer drugs that have strong host-guest interaction with SAC4A.
基金the National Natural Science Foundation of China (Grant Nos. 30570376 and 50673078)Shanghai Project (Grant Nos. 06JC14068 and 08ZZ21)
文摘Due to the nontoxicity and efficient anti-cancer activity, more and more attention has been paid to N-glycoside compounds. Laser photolysis of N-(α-D-glucopyranoside) salicyloyl hydrazine (NGSH) has been performed for the first time. The research results show that NGSH has high photosensitivity and is vulnerable to be photo-ionized via a monophotonic process with a quantum yield of 0.02, generating NGSH+· and hydrated electrons. Under the aerobic condition of cells, the hydrated electrons are very easy to combine with oxygen to generate 1O2 and O2-, both of which are powerful oxidants that can kill the cancer cells. In addition, NGSH+· can be changed into neutral radicals by deprotonation with a pKa value of 4.02 and its decay constant was determined to be 2.55×109dm3·mol-1·s-1. NGSH also can be oxidized by SO4-. with a rate constant of 1.76×109 dm3·mol-1.s-1, which further confirms the results of photoionization. All of these results suggest that this new N-glycoside compound might be useful for cancer treatment.
基金This study was supported by local special projects in major health of Hubei Provincial Science and Technology Department(2022BCE054)key scientific research projects of Hubei polytechnic University(23xjz08A).
文摘Taraxasterol(TS)is a naturally occurring pentacyclic triterpenoid extracted from the traditional Chinese herb Taraxacum mongolicum.Previous studies have highlighted its significant roles in exhibiting anti-inflammatory,anti-oxidant,and liver protective effects.In the present study,the anti-cancer potential of TS against cervical cancer was investigated,employing network pharmacology techniques,molecular docking,and in vitro experimental validation.TS exhibits its anticancer properties by modulating multiple targets,pathways,and biological processes.In vitro experiments demonstrated the potent inhibitory effects of TS on cancer cell growth and migration,while no significant impact on apoptosis was observed.The primary objective was to elucidate the anti-cancer potential of TS,which is a crucial lead compound in the treatment of cervical cancer.The findings may serve as a basis for the development of novel anticancer therapeutics and medicine-based interventions for cervical cancer.
基金Supported by Science and Technology Plan Project of Shaoyang City,No.2022GX4139.
文摘BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis(HT).While single symptomatic drug treatment of the two diseases is less effective,combined drug treatment may improve efficacy.AIM To investigate the effect of a combination of vitamin D,selenium,and hypoglycemic agents in T2DM with HT.METHODS This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023.Fifty patients were assigned to the control group,test group A,and test group B according to different treatment methods.The control group received low-iodine diet guidance and hypoglycemic drug treatment.Test group A received the control treatment plus vitamin D treatment.Test group B received the group A treatment plus selenium.Blood levels of markers of thyroid function[free T3(FT3),thyroid stimulating hormone(TSH),free T4(FT4)],autoantibodies[thyroid peroxidase antibody(TPOAB)and thyroid globulin antibody(TGAB)],blood lipid index[low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triacylglycerol(TG)],blood glucose index[fasting blood glucose(FBG),and hemoglobin A1c(HbA1c)]were measured pre-treatment and 3 and 6 months after treatment.The relationships between serum 25-hydroxyvitamin D3[25(OH)D3]level and each of these indices were analyzed.RESULTS The levels of 25(OH)D3,FT3,FT4,and LDL-C increased in the order of the control group,test group A,and test group B(all P<0.05).The TPOAB,TGAB,TC,TG,FBG,HbA1c,and TSH levels increased in the order of test groups B,A,and the control group(all P<0.05).All the above indices were compared after 3 and 6 months of treatment.Pre-treatment,there was no divergence in serum 25(OH)D3 level,thyroid function-related indexes,autoantibodies level,blood glucose,and blood lipid index between the control group,test groups A and B(all P>0.05).The 25(OH)D3 levels in test groups A and B were negatively correlated with FT4 and TGAB(all P<0.05).CONCLUSION The combination drug treatment for T2DM with HT significantly improved thyroid function,autoantibody,and blood glucose and lipid levels.
文摘Veterinary drugs are substances(including pharmaceutical feed additives)used to prevent,treat,and diagnose diseases or regulate the physiological functions of animals.Veterinary drug poisoning in humans is relatively rare both in China and the rest of the world.Here,we report a case of death from veterinary drug poisoning from avermectin-closantel.Avermectin-closantel is a broad-spectrum antiparasitic drug,which has high efficacy against a variety of trematodes and nematodes.