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1.
Org Biomol Chem ; 21(8): 1814-1820, 2023 Feb 22.
Article in English | MEDLINE | ID: mdl-36748884

ABSTRACT

A protocol for metal and oxidant free photoredox catalyzed trifluoromethylation of 2H-indazoles was developed by using Eosin Y as the photocatalyst and recoverable ionic liquids as the solvents. A series of trifluoromethylated products were obtained in moderate to good yields in this protocol under mild conditions. The reaction proceeded via a free-radical mechanism with a broad substrate range, excellent regioselectivity, and good functional group tolerance. Furthermore, the utility of this protocol was demonstrated by the synthesis of a highly selective ligand for estrogen receptor beta (ERß) and the drug granisetron. The protocol provides a mild and environmentally friendly solution for trifluoromethylation reaction.

2.
Adv Healthc Mater ; 11(10): e2102712, 2022 05.
Article in English | MEDLINE | ID: mdl-34981660

ABSTRACT

Here, the authors propose a light-activated reactive oxygen species (ROS)-responsive nanoplatform that can boost immunogenic cell death (ICD) to release "eat me" signals, and improve CD47-blocking immunotherapy by tumor-targeted codelivery of photosensitizer IR820 and anti-CD47 antibody (αCD47). Human serum albumin and αCD47 are first constructed into a single nanoparticle using ROS-responsive linkers, which are further conjugated with photosensitizer IR820 via a matrix metalloproteinase-sensitive peptide as linker and then modified with poly(ethylene glycol) on the surface of the obtained nanoparticles. When exposed to the first wave of near-infrared (NIR) laser irradiation, the obtained nanoplatform (M-IR820/αCD47@NP) can generate ROS, which triggers nanoparticles dissociation and thus, facilitates the release of αCD47 and IR820. The second wave of NIR laser irradiation is subsequently used to perform phototherapy and induce ICD of tumor cells. An in vitro cellular study shows that M-IR820/αCD47@NP can stimulate dendritic cells activation while simultaneously enhancing the phagocytic activity of macrophage against tumor cells. In 4T1 tumor-bearing mice, M-IR820/αCD47@NP-mediated combination of phototherapy and CD47 blockade can effectively induce the synergistic antitumor immune responses to inhibit the growth of tumors and prevent local tumor recurrence. This work offers a promising strategy to improve the CD47-blocking immunotherapy efficacy using αCD47 nanomedicine.


Subject(s)
Nanoparticles , Neoplasms , Animals , CD47 Antigen , Cell Line, Tumor , Immunologic Factors , Immunotherapy , Mice , Photosensitizing Agents/pharmacology , Reactive Oxygen Species
3.
Acta Biomater ; 119: 337-348, 2021 01 01.
Article in English | MEDLINE | ID: mdl-33166712

ABSTRACT

Nanomedicine-based chemoimmunotherapy has shown a great potential for cancer therapies application in recent years. However, most nanoparticles still face a problem of low accumulation and limited penetration of chemotherapeutic drugs and immunotherapeutic drugs into solid tumors. Here, we developed a tumor microenvironment (TME)-activable therapeutic peptide-conjugated prodrug nanoparticle for enhanced tumor penetration and synergistic antitumor effects of chemotherapy and immune checkpoint blockade therapy. The prodrug nanoparticle is composed of a short D-peptide antagonist of PD-L1 (DPPA) conjugated doxorubicin (DOX) prodrug and a PEGylated DOX prodrug, which can dissociate into small DOX nanoparticles (<30 nm) and release DPPA antagonist in TME. The prodrug nanoparticles could co-deliver DOX and DPPA antagonist by one nanocarrier and improve tumor accumulation and penetration of the prodrug nanoparticels via a transcytosis process. It is demonstrated that co-delivery of DOX and DPPA antagonist directly killed tumor cells, promoted the tumor-infiltrating cytotoxic T lymphocytes, reduced the tumor-infiltrating regulatory T cells, and elicited a long-term immune memory effect to prevent tumor recurrence and metastasis. This TME-activable prodrug nanoparticle holds promise as a co-delivery nanoplatform for the improved chemoimmunotherapy of solid tumors.


Subject(s)
Nanoparticles , Neoplasms , Prodrugs , Cell Line, Tumor , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Drug Delivery Systems , Humans , Neoplasms/drug therapy , Peptides/pharmacology , Peptides/therapeutic use , Prodrugs/pharmacology , Prodrugs/therapeutic use , T-Lymphocytes , Tumor Microenvironment
4.
Zhongguo Zhong Yao Za Zhi ; 45(16): 3988-3996, 2020 Aug.
Article in Chinese | MEDLINE | ID: mdl-32893599

ABSTRACT

This paper explores Mongolian medicine processing methods and the use regularity of excipient by text mining techniques. Relevant books of Mongolian medicine processing were consulted to collect data on Mongolian medicine processing methods and excipient, and select data based on processing methods and excipient noun frequency statistics. Microsoft Excel 2010 software was used for statistical analysis and mining for the usage regularity of different types of Mongolian medicinal materials in different periods. And Cytoscape 3.6.1 software was used for visual presentation. The topological analysis showed the top five processing methods were net production, development, frying, calcining and cooking, and the top five processing excipient were fresh milk, wine, urine, cream and mineral borax. Frequency analysis showed that the plant medicinal materials were mostly recorded in the 18~(th) and 21~(st) centuries, especially in the 21 st century; the processing methods mostly contained water processing, repair processing and other methods. The mineral medicinal materials were mostly recorded in the 18~(th), 19~(th) and 21~(st) centuries; most of the processing methods were the fire processing method. The animal medicinal materials were recorded in the 18~(th), 19~(th) and 21~(st) century; the fire processing method occupied a major position, and the repair processing and the grinding processing were markedly increased in the 21~(st) century. In the use of excipient, liquid excipient were mostly used in plant medicines. Solid excipient were most commonly used in the 18~(th) century. Animal excipient were mostly used during the processing in the 18~(th) century. The use of liquid excipient gradually increased in the 19~(th) and 21~(st) centuries. This study summarizes the traditional processing methods of Mongolian medicine and the usage regularity of excipient, defines the characteristics of Mongolian medicine processing methods and excipient, and the characteristics of the combination of medicinal materials and excipient, so as to provide reference for the clinical use of Mongolian medicine.


Subject(s)
Excipients , Medicine, Mongolian Traditional , Data Mining , Records , Software
5.
Biomaterials ; 242: 119933, 2020 Mar 02.
Article in English | MEDLINE | ID: mdl-32151859

ABSTRACT

Nanomedicine-based phototherapy in combination with immune checkpoint blockade therapy has been reported as a promising strategy for improved cancer immunotherapy. However, tumor penetration of nanomedicine into solid tumor is still an unresolved obstacle to an effective drug delivery, leading to limitations in their applications. Here, we developed a tumor microenvironment-responsive prodrug nanoplatform for efficient penetration and photo-immunotherapy of cancer. The prodrug nanoplatform is performed by integrating PEGylated indoleamine-2,3-dioxygenase (IDO) inhibitor (Epacadostat) and photosensitizer (Indocyanine green, ICG) into a core-shell nanostructure via intermolecular interactions, which can transform into small dual-drug complexes (<40 nm) at tumor microenvironment. The resulting small dual-drug complexes could undergo caveolae-mediated endocytosis, enhance cellular uptake, directly kill tumor cells, in situ trigger antitumor immune response and modulate IDO-mediated immunosuppression. More significantly, the prodrug nanoplatform in combination with PD-L1 checkpoint blockade synergistically promoted the antitumor immunity and efficiently inhibited the growth of both primary and abscopal tumors. The present study provides a novel delivery strategy for nanoenabled phototherapy and IDO inhibition to combine PD-L1 checkpoint blockade for achieving more effective therapy of solid tumors.

6.
Adv Healthc Mater ; 8(21): e1900660, 2019 11.
Article in English | MEDLINE | ID: mdl-31583853

ABSTRACT

Particle-based antigen carriers as adjuvants play an important role in vaccine development. Herein, an antigen-inorganic hybrid flower-like particle is developed as a novel vaccine carrier. Model antigen ovalbumin (OVA)-copper (II) sulfate hybrid vaccines (OVA-Cu-HVs) are mildly and facilely constructed through a biomimetic mineralization process. OVA-Cu-HVs facilitate cellular uptake in antigen-presenting cells and the internalization of OVA-Cu-HVs involves macropinocytosis-mediated endocytosis. OVA-Cu-HVs can release OVA in a pH-responsive behavior and promote cytosolic release of antigen to enhance antigen cross-presentation. Immunization with OVA-Cu-HVs promotes the maturation of dendritic cells in draining lymph nodes, induces robust antigen-specific T lymphocyte response, and inhibits tumor growth in vivo. In addition, OVA-Cu-HVs are efficacious after being stored for 4 weeks at room temperature and are expected to simplify vaccine storage and lower the cost of cold storage for transportation. Looking forward, OVA-Cu-HVs may hold strong potential to be as an effective vaccine delivery platform, which will facilitate the application of organic-inorganic hybrid flowers in biomedical areas.


Subject(s)
Antigens/chemistry , Vaccines/immunology , Animals , Antigen Presentation/immunology , Antigens/immunology , Cell Survival/physiology , Drug Delivery Systems/methods , Flow Cytometry , Mice , Nanoparticles/chemistry , Ovalbumin/chemistry , T-Lymphocytes, Cytotoxic/immunology , Temperature
7.
Acta Biomater ; 83: 390-399, 2019 01 01.
Article in English | MEDLINE | ID: mdl-30448435

ABSTRACT

Aluminum-based adjuvant (e.g., aluminum oxyhydroxide (AlO(OH), known as the commercial Alhydrogel® (Alum)) is the first adjuvant to be used in human vaccines. Although Alum shows a robust induction of antibody-mediated immunity, its weak stimulation of cell-mediated immunity makes it a questionable adjuvant for cancer immunotherapy. Herein, we described a novel formulation of Alum-based adjuvant by preparing AlO(OH)-modified graphene oxide (GO) nanosheets (GO-AlO(OH)), which, in addition to maintaining the induction of humoral immune response by AlO(OH), could further elicit the cellular immune response by GO. Similar to Alum, GO-AlO(OH) vaccine formulation could be constructed by the incorporation of antigen using a facile mixing/adsorption approach. Antigen-loaded GO-AlO(OH) nanocomplexes facilitated cellular uptake and cytosolic release of antigens and promoted DC maturation, thereby eliciting higher antigen-specific IgG titers, inducing robust CD4+ and CD8+ T lymphocyte response, and inhibiting tumor growth in vivo. Furthermore, by employing tumor cell lysate-based cancer vaccines, GO-AlO(OH) nanocomplexes led to significant inhibition of tumor growth and can be implemented as a personalized treatment strategy for cancer vaccine development. Overall, GO-AlO(OH) nanocomplexes described herein may serve as a facile and efficient approach for effective anticancer vaccination. STATEMENT OF SIGNIFICANCE: Herein, we described a novel formulation of aluminum-based adjuvant by preparing aluminum oxyhydroxide (AlO(OH)) (known as "Alum")-modified graphene oxide (GO) nanocomplexes (GO-AlO(OH)), which, in addition to maintaining the induction of humoral immune response by AlO(OH), could further elicit the cellular immune response by GO. GO-AlO(OH) nanocomplexes can be prepared easily and in large scale by a chemical precipitation method. Similar to "Alum," antigen-loaded GO-AlO(OH) vaccine formulation could be constructed by the incorporation of antigen using a facile mixing/adsorption approach. The very simple and reproductive preparation process of vaccines and the powerful ability to raise both humoral and cellular immune responses provide a novel approach for improving cancer immunotherapy efficacy.


Subject(s)
Adjuvants, Immunologic , Alum Compounds , Antigens, Neoplasm , Graphite , Melanoma, Experimental , Nanostructures , Adjuvants, Immunologic/chemistry , Adjuvants, Immunologic/pharmacology , Alum Compounds/chemistry , Alum Compounds/pharmacology , Animals , Antigens, Neoplasm/chemistry , Antigens, Neoplasm/immunology , Antigens, Neoplasm/pharmacology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/pathology , Cancer Vaccines , Dendritic Cells/immunology , Dendritic Cells/pathology , Graphite/chemistry , Graphite/pharmacology , Immunity, Cellular/drug effects , Melanoma, Experimental/immunology , Melanoma, Experimental/pathology , Melanoma, Experimental/therapy , Mice , Nanostructures/chemistry , Nanostructures/therapeutic use
8.
ACS Appl Mater Interfaces ; 11(2): 1876-1885, 2019 Jan 16.
Article in English | MEDLINE | ID: mdl-30582788

ABSTRACT

Despite the potential efficacy of immune checkpoint blockade for effective treatment of cancer, this therapeutic modality is not generally curative, and only a fraction of patients respond. Combination approaches provide strategies to target multiple antitumor immune pathways to induce synergistic antitumor immunity. Here, a multi-combination immunotherapy, including photothermal therapy (PTT), indoleamine-2,3-dioxygenase (IDO) inhibition, and programmed cell death-ligand 1 (PD-L1) blockade, is introduced for inducing synergistic antitumor immunity. We designed a multifunctional IDO inhibitor (IDOi)-loaded reduced graphene oxide (rGO)-based nanosheets (IDOi/rGO nanosheets) with the properties to directly kill tumor cells under laser irradiation and in situ trigger antitumor immune response. In vivo experiments further revealed that the triggered immune response can be synergistically promoted by IDO inhibition and PD-L1 blockade; the responses included the enhancement of tumor-infiltrating lymphocytes, including CD45+ leukocytes, CD4+ T cells, CD8+ T cells, and NK cells; the inhibition of the immune suppression activity of regulator T cells (Tregs); and the production of INF-γ. We also demonstrate that the three combinations of PTT, IDO inhibition, and PD-L1 blockade can effectively inhibit the growth of both irradiated tumors and tumors in distant sites without PTT treatment. This work can be thought of as an important proof of concept to target multiple antitumor immune pathways to induce synergistic antitumor immunity.


Subject(s)
B7-H1 Antigen/antagonists & inhibitors , Graphite , Hyperthermia, Induced , Immunity, Cellular , Indoleamine-Pyrrole 2,3,-Dioxygenase , Neoplasms, Experimental , Phototherapy , Animals , B7-H1 Antigen/immunology , CD8-Positive T-Lymphocytes/immunology , Cell Line, Tumor , Female , Graphite/chemistry , Graphite/pharmacology , Humans , Immunity, Cellular/drug effects , Immunity, Cellular/radiation effects , Indoleamine-Pyrrole 2,3,-Dioxygenase/antagonists & inhibitors , Indoleamine-Pyrrole 2,3,-Dioxygenase/immunology , Interferon-gamma/immunology , Killer Cells, Natural/immunology , Killer Cells, Natural/pathology , Mice , Mice, Inbred BALB C , Neoplasms, Experimental/immunology , Neoplasms, Experimental/pathology , Neoplasms, Experimental/therapy , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/pathology
9.
Zhongguo Zhong Yao Za Zhi ; 43(16): 3412-3416, 2018 Aug.
Article in Chinese | MEDLINE | ID: mdl-30200749

ABSTRACT

Standardization is the progress of human civilization. It is also an important technical system for normalizing economy and social development and a basic element in the core competitive power of a country. This paper emphasized on the importance of accelerating the standardization of Mongolian medicine for international development of national medicine and improving the international competitiveness. Summed up the Mongolian medicine standardization work achieved the stage results. Achievements on Mongolian medicine standardization were summarized and the existed problems were also analyzed. Such as, imperfect Mongolian medicine standard system and operation mechanism, the lack of application and personnel of Mongolian medicine. Corresponding measures, such as improving the Mongolian medicine standardization system and its support system construction; establishing personnel long-term training mechanism; the establishment of Mongolian medicine standard implementation-promotion-evaluation-feedback mechanism and other corresponding measures, were also provide.


Subject(s)
Medicine, Mongolian Traditional , Humans , Reference Standards
10.
Medicine (Baltimore) ; 97(9): e9884, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29489687

ABSTRACT

RATIONALE: Idiopathic hypoparathyroidism (IHP) is a rare endocrine condition, which is frequently represented by neuropsychiatric disorders. Hence, the misdiagnosis rate of the disease is rather high, especially for neurologists. PATIENT CONCERNS: We reported a case of misdiagnosed, atypical IHP. In addition, the literature on IHP and the misdiagnosis published in China in the past 2 decades has been reviewed and summarized. DIAGNOSES: Blood testing confirmed that parathyroid hormone (PTH) = 0 pg/mL and the final diagnosis was IHP. INTERVENTIONS AND OUTCOMES: With calcium and vitamin D supplementation, the patient's myasthenia improved significantly, and muscle enzymes returned to normal gradually. One-year follow-up demonstrated that the patient's myasthenia disappeared, and the blood calcium and PTH levels were normal. In addition, the literature on IHP and the misdiagnosis published in China in the past 2 decades has been reviewed and summarized. LESSONS: The misdiagnosis rate of IHP in China was high in the past 2 decades, which might be attributed to the misdiagnosis as epilepsy or mental diseases. A clinician should be able to understand the disease and emphasize the screening of high-risk population, especially for those patients with hypocalcemia, hyperphosphatemia, and increased blood creatine kinase with unknown causes or nontypical clinical symptoms.


Subject(s)
Diagnostic Errors/adverse effects , Hypoparathyroidism/diagnosis , Adult , Female , Humans , Hypoparathyroidism/drug therapy , Parathyroid Hormone/blood
11.
Zhongguo Zhong Yao Za Zhi ; 42(5): 998-1004, 2017 Mar.
Article in Chinese | MEDLINE | ID: mdl-28994546

ABSTRACT

Mongolian medicine is the traditional drug with the theory of Mongolian medicine and pharmacy as a guide, which made a great contribution to the survival and development of the Mongolian people. Mongolian medicine "Bashaga" faced the situations of origin is unclear, and clinical therapy is confused and so on. This paper summarizes the original plants and studies the species textual research and ethnopharmacology of Mongolian medicine "Bashaga". This paper intends to ensure authentic plant and provide comprehensive insight into the chemical constituents, pharmacology and application status of Mongolian medicine "Bashaga" to discuss the rationality of the confirmation in "Bashaga" authentic plant.


Subject(s)
Ethnopharmacology , Medicine, Mongolian Traditional , Plants, Medicinal/chemistry , Research
12.
Anal Chim Acta ; 963: 143-152, 2017 Apr 22.
Article in English | MEDLINE | ID: mdl-28335968

ABSTRACT

In this study, multi-acrylate based dipentaerythritol penta-/hexa-acrylate (DPEPA) was exploited for fabrication of highly cross-linked hybrid monolithic column by copolymerization with polyhedral oligomeric silsesquioxane methacryl substituted (POSS-MA) via a "one-pot" method. The new DPEPA-POSS hybrid monolithic column was respectively characterized by Fourier transform infrared spectrometry, thermogravimetric analysis, scanning electron microscopy and nitrogen adsorption/desorption measurement. When it was used for the separation of amides, thioureas and positional isomers of phenols, ultrahigh column efficiency separation (up to 511,000 N m-1) was achieved with excellent selectivity. Moreover, intact protein standards could be efficiently separated with minimum tailing peaks, outperforming the commercially available silica-based C8 column. Furthermore, successful separation of complex egg white proteins and expressed BARD1 BRCT domains protein sample was also achieved with good chromatographic performance. In the future work, the DPEPA-POSS hybrid monolithic column will be further exploited and applied in capillary electrochromatography as well as the top-down based proteome research.


Subject(s)
Acrylic Resins/chemistry , Chromatography, High Pressure Liquid/methods , Proteins/isolation & purification , Animals , Cattle , Protein Domains , Proteins/chemistry
13.
ACS Appl Mater Interfaces ; 8(33): 21632-9, 2016 Aug 24.
Article in English | MEDLINE | ID: mdl-27483161

ABSTRACT

In this study, new metal-organic frameworks (MOFs) nanocrystals modified SiO2 core-shell microspheres were designed with cationic ionic liquids (ILs) 1,3-bis(4-carboxybutyl)imidazolium bromide (ILI) as organic ligands. By further adjustment the growth cycles, the new ILI-01@SiO2 core-shell stationary phase was facilely fabricated. The developed stationary phase was respectively characterized via element analysis, thermogravimetric analysis, scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectrometry. Because the introduction of cationic imidazolium-based ILs ILI for fabrication of the MOFs nanocrystals shell, the new stationary phase exhibits the retention mechanism of hydrophilic interaction liquid chromatography (HILIC). Many polar samples, such as amides, vitamins, nucleic acid bases, and nucleosides, were utilized to investigate the performance of the prepared ILI-01@SiO2 column. Compared to the conventional aminosilica column, the new ILI-01@SiO2 column displays high separation selectivity in a shorter separation time. Furthermore, the new ILI-01@SiO2 column was also used for detection of illegal melamine addition in the baby formula. All the above results demonstrate the new ILI-01@SiO2 core-shell stationary phase is of good potentials for high-selectivity separation the polar samples.

14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 23(3): 779-84, 2015 Jun.
Article in Chinese | MEDLINE | ID: mdl-26117036

ABSTRACT

OBJECTIVE: To investigate the effect of bear bile powder and ursodesxy cholic acid (UDCA) on peripheral blood, bone marrow megakaryocyte and immune organs in mouse model with thrombocytopenia, so as to provide a reference for studying the curative effects of bear bile powder and its succedaneum on thrombocytopenic purpura (TP). METHODS: The mouse model with thrombocytopenia indued by cytosine arabinoside (Ara-C) was established, a total of 70 mice were randomly divided into normal group, model group, prednisone group, bear bile (middle and high dose) powder group and UDCA (middle and high dose) group. From the first day of making model mice in the each group, 0.4 ml/(20 g·d) corresponding drug was administered by infusion. At day 10 after treatment the peripheral blood, spleen and thymus organ index, the number of bone marrow megakaryocyte in each group were compared. RESULTS: compared with the normal group, the Plt, WBC and megakaryocyte counts in model group decreased, the spleen index increased obviously (P<0.05), but the WBC count returned to normal by 10 days; after treatment, compared with model group, the Plt, WBC and megakaryocyte counts of treated groups increased, spleen index decreased significantly (P<0.05), but the WBC count in prednisone group decreased, which in bear bile powder (high) group and UDCA (high) group were particularly significant. CONCLUSION: The bear bile powder and UDCA have been confirmed to have therapeutical effect on thrombocytopenia models induced by Ara-C, UDCA can substitute bear bile powder as a treatment drug for thrombocytopenic purpura.


Subject(s)
Bone Marrow , Cytarabine , Megakaryocytes , Thrombocytopenia , Animals , Bile , Bone Marrow Cells , Disease Models, Animal , Mice , Spleen
15.
Int J Clin Exp Med ; 8(2): 2934-8, 2015.
Article in English | MEDLINE | ID: mdl-25932258

ABSTRACT

BACKGROUND: Polymorphisms of DNA repair genes may affect the repair capacity of DNA damages and cause different responses towards chemotherapy. Excision repair cross-complementing group 2 (ERCC2) plays an important role in the nucleotide excision repair. OBJECTIVES: The aim of this study was to investigate the association between ERCC2 single nucleotide polymorphisms (SNPs) and the response to platinum-based chemotherapy among patients with triple negative breast cancer. METHODS: In total, 60 triple negative breast cancer patients treated with platinum-based chemotherapy were studied. The clinical, pathological and treatment data of them were collected. Sequenom's MassARRAY system was used in the detection of the SNPs of ERCC2. Finally, the association between genotypes and different clinical responses among patients was analyzed. All of the patients received a platinum-based chemotherapy for 4 cycles in median and achieved an overall response rate of 66.7%, showing a comparative good response towards platinum-based chemotherapy among triple negative breast cancer. Fifty-three of the 60 patients had got the results of ERCC2 rs1799793 polymorphisms after MassARRAY detection. RESULTS: The proportion of GG genotype and GA genotype was 81.1% and 18.9% respectively. The response rate of the rs1799793 GG genotype group was 69.8%, while the GA genotype group only had a response rate of 30.0%. It turned out that the GG genotype was associated with better response towards platinum-based chemotherapy (P=0.030). CONCLUSIONS: ERCC2 rs1799793 polymorphism may be associated with the clinical sensitivity of platinum-based chemotherapy and could be a potential predictive biomarker for triple negative breast cancer patients treated with platinum compounds.

16.
Cell Physiol Biochem ; 34(5): 1663-74, 2014.
Article in English | MEDLINE | ID: mdl-25401481

ABSTRACT

BACKGROUND/AIMS: CpG-oligodeoxynucleotides (ODNs) are synthetic DNA sequences containing unmethylated cytosine-guanine motifs with potent immunomodulatory effects. Previous reports showed a powerful protective effect of CpG-ODN against the damage induced by low-LET γ-rays. In this study, we explored whether CpG-ODN also protects against the damage induced by high-LET irradiation. Parallel experiments were performed with low-LET irradiation. METHODS: RAW264.7 cells were incubated with 1 µM of CpG-ODN after γ-ray or carbon-beam irradiation. Cell death was then measured by PI/DAPI double staining, cell survival was assessed by colony-formation assays, DNA damage was evaluated by comet assays, cell cycle was monitored by flow cytometry, and the levels of apoptosis-related proteins were detected by western blots. RESULTS: When irradiated cells were treated with the CpG-ODN, cell viability decreased, cell survival increased, DNA damage and G2/M-phase arrest were ameliorated, and apoptosis was inhibited. CONCLUSIONS: The CpG-ODN showed protective effects against low-LET γ-ray and high-LET carbon-beam irradiation. These effects might be associated with the repair of DNA damage and inhibition of apoptosis.


Subject(s)
Cell Survival/drug effects , DNA Damage/drug effects , Gamma Rays/adverse effects , Oligodeoxyribonucleotides/pharmacology , Protective Agents/pharmacology , Animals , Apoptosis/drug effects , Apoptosis/radiation effects , Cell Cycle Checkpoints/drug effects , Cell Cycle Checkpoints/radiation effects , Cell Line , Cell Survival/genetics , Cell Survival/radiation effects , DNA Damage/radiation effects , G2 Phase Cell Cycle Checkpoints/drug effects , G2 Phase Cell Cycle Checkpoints/radiation effects , Mice
17.
Arch Gynecol Obstet ; 290(1): 155-62, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24573504

ABSTRACT

PURPOSE: To investigate the contribution of uterine arterial chemoembolization (UACE) and uterine arterial infusion chemotherapy (UAIC) to advanced cervical cancer before radical radiotherapy. METHODS: A total of 735 patients with primary advanced cervical cancer were retrospectively studied; of these patients, 299 were classified as FIGO stage II, 359 as stage III and 77 as stage IVa. 126 underwent UACE, 103 underwent UAIC before radiotherapy, and 506 received radical radiotherapy alone (RT). Disease-specific survival (DSS), pelvic control (PC), distant metastasis-free survival (MFS), and risk factors of late toxicity were analyzed. RESULTS: The 1-, 2-, 5-, and 8-year DSS of all patients was 94.4, 82.1, 50.2, and 30.7 %, respectively. The DSS of the UACE group was 96.0, 83.4, 39.6, 18.3 %; UAIC group was 95.6, 84.3, 59.6, 42.7 % and RT group was 93.7, 80.8, 51.5, 31.5 % (χ (2) = 10.236, P = 0.006). The 1- and 2-year DSS of the UAIC and UACE groups was higher than those of the RT group (χ (2) = 2.510, P = 0.285; χ (2) = 2.822, P = 0.244). The 5- and 8-year DSS of the UACE group was obviously decreased (χ (2) = 14.962, P = 0.001; χ (2) = 14.043, P = 0.001). PC and MFS were highest in the UAIC group and lowest in the UACE group. The incidence of late radiation toxicity of the small intestine and rectosigmoid was similar. The bladder injury was highest in the UACE group (UACE:UAIC:RT = 11.1:4.8:4.2 %, χ (2) = 9.579, P = 0.008). UACE is a risk factor for late radiation toxicity of the urinary bladder. CONCLUSIONS: The use of UAIC before radical radiotherapy could improve the treatment outcome and prognosis of patients with advanced cervical cancer, while the UACE would significantly decrease long-time survival. UACE is an important risk factor for late radiation toxicity.


Subject(s)
Adenocarcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Brachytherapy/methods , Carcinoma, Squamous Cell/therapy , Infusions, Intra-Arterial , Uterine Artery Embolization , Uterine Cervical Neoplasms/therapy , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Chemoradiotherapy , Dose-Response Relationship, Radiation , Female , Follow-Up Studies , Humans , Middle Aged , Multivariate Analysis , Neoplasm Staging , Prognosis , Proportional Hazards Models , Retrospective Studies , Risk Factors , Severity of Illness Index , Survival Rate , Treatment Outcome , Uterine Cervical Neoplasms/mortality , Uterine Cervical Neoplasms/pathology
18.
Zhongguo Yi Liao Qi Xie Za Zhi ; 36(6): 456-8, 2012 Nov.
Article in Chinese | MEDLINE | ID: mdl-23461129

ABSTRACT

OBJECTIVE: To explore clinical value of circular DNA in acute myocardial infarction. METHODS: Venous blood (2 ml/head) of 40 healthy control and 40 patients with acute myocardial infarction within 48h of onset of illness and convalescent period was collected. The level of plasma circular DNA was detected by duplex real-time polymerase chain reaction assay. The levels of myocardial enzyme spectrum and cardiac troponin T (cTnT) were detected by biochemistry method. RESULTS: The level of circular DNA in control group and group of acute myocardial infarction before treatment was (21.5 +/- 10.7) ng/ml and (253.6 +/- 45.7) ng/ml, respectively (P = 0.000). The levels of serum myocardial enzyme spectrum and cTnT before treatment in patients with acute myocardial infarction were significantly higher than those of control group (P < 0.05). The level of circular DNA after treatment in patients with acute myocardial infarction was significantly decreased compared with that before treatment (P = 0.000), the levels of myocardial enzyme spectrum and cTnT were also significantly reduced (P < 0.05). There was significant correlation between the level of circular DNA and those of CK-MB and cTnT, r = 0.613, 0.654, P = 0.032, 0.021. CONCLUSION: Circular DNA can be used as a marker of sensitively reflecting myocardial cell injury.


Subject(s)
DNA, Circular/blood , Myocardial Infarction/blood , Myocardial Infarction/diagnosis , Aged , Case-Control Studies , Female , Humans , Male , Middle Aged
19.
Zhonghua Fu Chan Ke Za Zhi ; 45(7): 506-10, 2010 Jul.
Article in Chinese | MEDLINE | ID: mdl-21029602

ABSTRACT

OBJECTIVE: To investigate the long-term curative effect of the radiotherapy combined uterine arterial interventional chemoembolization for cervical cancer. METHODS: Records of 632 patients with cervical cancer stage II - IVa proved by pathology in Lanzhou Command General Hospital from January 1st, 1999 to August 31st, 2009 were retrospective analysed. One hundred and twenty-six cases of them were treated with radical radiotherapy combined uterine arterial interventional chemoembolization (arterial chemoembolization + radiotherapy group), 506 cases of them were treated with radical radiotherapy only (radiotherapy group); the evaluation of the late radiation injury was done, according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) advanced radiation injury criteria. Prognosis and complications were compared between two groups, relative risk factors of radiotherapy complications were identified by method of logistic regression. RESULTS: (1) Survival: the total survival rates of 1-year, 2-year, 5-year and 8-year were 94.4%, 82.3%, 48.8%, 29.1%, respectively. The survival rates of arterial chemoembolization + radiotherapy group were 96.0%, 82.1%, 37.2%, 25.7%, while the survival rates of radiotherapy group were 94.1%, 80.8%, 51.1%, 31.5%, in which there were significant differences between two groups (χ(2) = 0.009, P = 0.993; χ(2) = 0.158, P = 0.691; χ(2) = 11.197, P = 0.001;χ(2) = 9.649, P = 0.002). During the follow-up period, the rate of recurrence and metastasis in arterial chemoembolization + radiotherapy group were 77.0% (97/126), while 73.3% (371/506) in radiotherapy group (χ(2) = 0.705, P = 0.401). (2) Radiotherapy complications and relative risk factors: the total incidence of tardive bladder injury higher than RTOG/EORTC stage II was 5.5% (35/632), while it was 11.1% (14/126) in arterial chemoembolization + radiotherapy group, 4.2% (21/506) in the radiotherapy group (χ(2) = 9.344, P = 0.002). The results of logistic regression showed that the uterine arterial interventional chemoembolization was relative risk factors of the tardive bladder injury (χ(2) = 6.440, OR = 2.869, P = 0.011). CONCLUSIONS: Compared with the simple radiotherapy, there are a similar short-term survival rate and significant poor 5-year, 8-year survival rate in the patients treated with the uterine arterial interventional chemoembolization combined with radiotherapy, which also may be strong dangerous factor for the occurrence of tardive bladder injury. The results shown that the uterine arterial interventional chemoembolization do not recommend to be routine adjuvant therapy for the radical radiotherapy of cervical cancer.


Subject(s)
Antimetabolites, Antineoplastic/administration & dosage , Carcinoma, Squamous Cell/therapy , Chemoembolization, Therapeutic , Cisplatin/administration & dosage , Fluorouracil/administration & dosage , Radiotherapy , Uterine Cervical Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Cisplatin/therapeutic use , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Cyclophosphamide/therapeutic use , Female , Fluorouracil/therapeutic use , Follow-Up Studies , Humans , Infusions, Intra-Arterial , Middle Aged , Neoplasm Staging , Prognosis , Radiography, Interventional , Retrospective Studies , Survival Rate , Treatment Outcome , Uterine Artery , Uterine Cervical Neoplasms/mortality , Uterine Cervical Neoplasms/pathology , Young Adult
20.
Article in Chinese | MEDLINE | ID: mdl-15323439

ABSTRACT

OBJECTIVE: To analyze the epidemiological features of clavicle fractures. METHODS: A total of 363 cases of clavicle fractures were treated from February 1993 to November 2002, their case history data were reviewed and evaluated by epidemiological method. RESULTS: Out of 363 cases, there were 269 males and 94 females, aged from new born to 96 years. The locations of fractures were on left side in 159 cases and on right side in 204 cases. Neonatal clavicle fracture occurred in the case of delivery (0.28%). The causes of disease for adult clavicle fractures were traffic injury (52.1%) and daily falling injury (31.1%). There were 232 cases of simple fractures and 131 cases of comminuted fractures. The fracture positions included inner (6 cases), middle (328 cases) and outer parts (29 cases). Multi-injuries occurred in 78 cases, the rib fractures concomitant with clavicle fractures were the commonest (31 cases). CONCLUSION: The clavicle fractures are the common injury. Of them, traffic injury and daily falling injury are the most common. The rib fractures are always accompanied with clavicle fractures. The main position of fracture is on the middle part.


Subject(s)
Clavicle/injuries , Fractures, Bone/epidemiology , Fractures, Comminuted/epidemiology , Accidents, Traffic , Adolescent , Adult , Aged , Aged, 80 and over , Child , China/epidemiology , Female , Fractures, Bone/complications , Humans , Incidence , Infant , Infant, Newborn , Male , Middle Aged , Multiple Trauma/epidemiology , Rib Fractures/complications , Rib Fractures/epidemiology
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