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BACKGROUND: Nonylphenol (NP) and bisphenol A (BPA) are produced in large quantities worldwide as multipurpose agents. However, studies on relations between NP and BPA exposure and childhood neurodevelopment are few, and the results are inconsistent. This study aimed to investigate associations between prenatal and early childhood NP and BPA exposure and neurodevelopment in mother-child pairs. METHODS: Pregnant women at 27-38 weeks' gestation were recruited, as were children 2-3 years of age (n = 94) and 4-6 years of age (n = 56) years. Urine was collected to assess NP and BPA exposure. Bayley Scales of Infant and Toddler Development (3rd edition; Bayley-III), Wechsler Preschool and Primary Scale of Intelligence (4th edition), and the Full Scale Intelligence Quotient (WPPSI-IV-FSIQ) were used to assess the neurodevelopment of the children. RESULTS: The detection rate and concentration of NP and BPA in the urine of children 4-6 years old were higher than in those 2-3 years old. Children were divided into a high concentration group (3rd tertile) and a reference group (1st and 2nd tertiles) based on natural log-transformed urine concentration of NP and BPA. Girls' Bayley-III motor scores in the high concentration group were higher than those of the BPA reference group of urine of mothers (ß = 6.85, 95% confidence interval [CI]: 1.58-12.13). Boys' FSIQ in the higher concentration group were significantly lower than those in children 2-3 years old in the NP reference group (ß = -11.29, 95% CI: -18.62 to -3.96) (all, p < 0.05). CONCLUSIONS: Prenatal and childhood exposure to NP and BPA may have different effects on the neurodevelopment of young children, and there are no consistent effects between boys and girls.
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Effets différés de l'exposition prénatale à des facteurs de risque , Mâle , Nourrisson , Humains , Enfant d'âge préscolaire , Femelle , Grossesse , Adulte d'âge moyen , Enfant , Phénols/toxicité , Phénols/urine , Composés benzhydryliques/toxicité , Composés benzhydryliques/urine , VitaminesRÉSUMÉ
PURPOSE: Ablative radiation therapy (RT) is an important strategy to eliminate primary tumor and can potentially induce the abscopal effect. Human serum albumin nanoparticle (NP) was used for controlled release of cisplatin to decrease cisplatin's systemic toxicity, and gold (Au) was added to increase RT-induced immunogenic cell death and potentiate the abscopal antitumor immunity. METHODS AND MATERIALS: The designed albumin-based cisplatin-conjugated AuNPs were administered concurrently with ablative RT. C57BL/6 mice implanted with syngeneic murine Lewis lung carcinoma or murine MB49 tumor models were treated with ablative RT (12 Gy per fraction for 2 fractions, total 24 Gy), cisplatin, or Au-cisplatin NPs. RESULTS: Combining ablative RT with cisplatin or Au-cisplatin NPs both destroyed the primary tumor effectively and elicited immunogenic cell death accompanied by release of danger-associated molecular patterns. This enhanced recruitment of effector tumor-infiltrating immune cells, including natural killer T cells and CD8+ T cells, and elicited an increased percentage of professional antigen-presenting CD11c+ dendritic cells. Transient weight loss, accompanying hepatotoxicity, nephrotoxicity, and hematopoietic suppression, was observed as a systemic adverse event in the cisplatin but not the Au-cisplatin NPs group. Cisplatin and Au-cisplatin NPs both showed equivalent ability to reduce metastatic potential when combined with ablative RT, confirmed by suppressed unirradiated flank tumor growth and decreased metastatic lung tumor burden, which translated to improved survival. Mobilization and abundance of effector tumor-infiltrating immune cells including CD8+ T cells and dendritic cells were observed in the distant lung tumor microenvironment after ablative RT with cisplatin or Au-cisplatin NPs, demonstrating increased antitumor immunotherapeutic activity as an abscopal effect. CONCLUSIONS: Compared with cisplatin, the albumin-based Au-cisplatin NPs exhibited equivalent but no superior antitumor immunotherapeutic activity while reducing systemic adverse events and can be safely administered concurrently with ablative RT. Alternative NP formulations may be designed to further improve anticancer outcomes.
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Carcinome pulmonaire de Lewis , Nanoparticules métalliques , Animaux , Souris , Humains , Cisplatine/pharmacologie , Or , Souris de lignée C57BL , Microenvironnement tumoral , Carcinome pulmonaire de Lewis/traitement médicamenteux , Carcinome pulmonaire de Lewis/radiothérapie , Lymphocytes T CD8+ , Albumines , Lignée cellulaire tumoraleRÉSUMÉ
Helicobacter pylori infection usually causes gastrointestinal complications, including gastrointestinal bleeding or perforation, and serious infections may lead to gastric cancer. Amoxicillin is used to treat numerous bacterial infections but is easily decomposed in the gastric acid environment via the hydrolyzation of the ß-lactam ring. In this study, we develop chitosan-based nanoparticles loaded with amoxicillin (CAANs) as an H. pylori eradication platform. The CAANs were biocompatible and could retain the antibiotic activity of amoxicillin against H. pylori growth. The mucoadhesive property of chitosan and alginate enabled the CAANs to adhere to the mucus layers and penetrate through these to release amoxicillin in the space between the layers and the gastric epithelium. The use of this nanoparticle could prolong the retention time and preserve the antibiotic activity of amoxicillin in the stomach and help enhance the eradication rate of H. pylori and reduce treatment time. These CAANs, therefore, show potential for the effective treatment of highly antibiotic-resistant H. pylori infection using amoxicillin.
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Osteoporosis is a disease that reduces bone mass and microarchitecture, which makes bones fragile. Postmenopausal osteoporosis occurs due to estrogen deficiency. Raloxifene is a selective estrogen receptor modulator used to treat postmenopausal osteoporosis. However, it has a low bioavailability, which requires long-term, high-dose raloxifene administration to be effective and causes several side effects. Herein, raloxifene was encapsulated in human serum albumin (HSA)-based nanoparticles (Ral/HSA/PSS NPs) as an intravenous-injection pharmaceutical formulation to increase its bioavailability and reduce the treatment dosage and time. In vitro results indicated that raloxifene molecules were well distributed in HSA-based nanoparticles as an amorphous state, and the resulting raloxifene formulation was stabile during long-term storage duration. The Ral/HSA/PSS NPs were both biocompatible and hemocompatible with a decreased cytotoxicity of high-dose raloxifene. Moreover, the intravenous administration of the prepared Ral/HSA/PSS NPs to rats improved raloxifene bioavailability and improved its half-life in plasma. These raloxifene-loaded nanoparticles may be a potential nanomedicine candidate for treating postmenopausal osteoporosis with lower raloxifene dosages.
Sujet(s)
Nanoparticules , Ostéoporose post-ménopausique , Animaux , Biodisponibilité , Femelle , Humains , Ostéoporose post-ménopausique/induit chimiquement , Ostéoporose post-ménopausique/traitement médicamenteux , Chlorhydrate de raloxifène , Rats , Modulateurs sélectifs des récepteurs des oestrogènes , Sérum-albumine humaineRÉSUMÉ
Aim: 7-Ethyl-10-hydroxycamptothecin (SN-38)-loaded gold nanoshells nanoparticles (HSP@Au NPs) were developed for combined chemo-photothermal therapy to treat colorectal cancer. Materials & methods: SN-38-loaded nanoparticles (HSP NPs) were prepared by the lyophilization-hydration method, and then developed into gold nanoshells. The nanoparticles were characterized and assessed for photothermal properties, cytotoxicity and hemocompatibility in vitro. In vivo anticancer activity was tested in a tumor mouse model. Results: The HSP@Au NPs (diameter 186.9 nm, zeta potential 33.4 mV) led to significant cytotoxicity in cancer cells exposed to a near-infrared laser. Moreover, the HSP@Au NP-mediated chemo-photothermal therapy displayed significant tumor growth suppression and disappearance (25% of tumor clearance rate) without adverse side effects in vivo. Conclusion: HSP@Au NPs may be promising in the treatment of colorectal cancer in the future.
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Tumeurs colorectales , Nanocoquilles , Animaux , Lignée cellulaire tumorale , Tumeurs colorectales/traitement médicamenteux , Doxorubicine/usage thérapeutique , Irinotécan , Souris , Photothérapie , Thérapie photothermiqueRÉSUMÉ
BACKGROUND: Lung cancer is the leading cause of cancer patient death in the world. There are many treatment options for lung cancer, including surgery, radiation therapy, chemotherapy, targeted therapy, and combined therapy. Despite significant progress has been made in the diagnosis and treatment of lung cancer during the past few decades, the prognosis is still unsatisfactory. PURPOSE: To resolve the problem of chemotherapy failure, we developed a magnetite-based nanomedicine for chemotherapy acting synergistically with loco-regional hyperthermia. METHODS: The targeting carrier consisted of a complex of superparamagnetic iron oxide (SPIO) and poly(sodium styrene sulfonate) (PSS) at the core and a layer-by-layer shell with cisplatin (CDDP), together with methotrexate - human serum albumin conjugate (MTX-HSA conjugate) for lung cancer-specific targeting, referred to hereafter as SPIO@PSS/CDDP/HSA-MTX nanoparticles (NPs). RESULTS: SPIO@PSS/CDDP/HSA-MTX NPs had good biocompatibility and stability in physiological solutions. Furthermore, SPIO@PSS/CDDP/HSA-MTX NPs exhibited a higher temperature increase rate than SPIO nanoparticles under irradiation by a radiofrequency (RF) generator. Therefore, SPIO@PSS/CDDP/HSA-MTX NPs could be used as a hyperthermia inducer under RF exposure after nanoparticles preferentially targeted and then accumulated at tumor sites. In addition, SPIO@PSS/CDDP/HSA-MTX NPs were developed to be used during combined chemotherapy and hyperthermia therapy, exhibiting a synergistic anticancer effect better than the effect of monotherapy. CONCLUSION: Both in vitro and in vivo results suggest that the designed SPIO@PSS/CDDP/HSA-MTX NPs are a powerful candidate nanoplatform for future antitumor treatment strategies.
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Oxyde ferrosoferrique/composition chimique , Hyperthermie provoquée , Tumeurs du poumon/thérapie , Nanomédecine/méthodes , Animaux , Lignée cellulaire tumorale , Cisplatine/composition chimique , Cisplatine/usage thérapeutique , Association thérapeutique , Vecteurs de médicaments/composition chimique , Humains , Tumeurs du poumon/traitement médicamenteux , Méthotrexate/composition chimique , Nanoparticules/composition chimique , Sérumalbumine/composition chimiqueRÉSUMÉ
Helicobacter pylori infection is one of the leading causes of several gastroduodenal diseases, such as gastritis, peptic ulcer, and gastric cancer. In fact, H. pylori eradication provides a preventive effect against the incidence of gastric cancer. Amoxicillin is a commonly used antibiotic for H. pylori eradication. However, due to its easy degradation by gastric acid, it is necessary to administer it in a large dosage and to combine it with other antibiotics. This complexity and the strong side effects of H. pylori eradication therapy often lead to treatment failure. In this study, the chitosan/poly (acrylic acid) particles co-loaded with superparamagnetic iron oxide nanoparticles and amoxicillin (SPIO/AMO@PAA/CHI) are used as drug nano-carriers for H. pylori eradication therapy. In vitro and in vivo results show that the designed SPIO/AMO@PAA/CHI nanoparticles are biocompatible and could retain the biofilm inhibition and the bactericidal effect of amoxicillin against H. pylori. Moreover, the mucoadhesive property of chitosan allows SPIO/AMO@PAA/CHI nanoparticles to adhere to the gastric mucus layer and rapidly pass through the mucus layer after exposure to a magnetic field. When PAA is added, it competes with amoxicillin for chitosan, so that amoxicillin is quickly and continuously released between the mucus layer and the gastric epithelium and directly acts on H. pylori. Consequently, the use of this nano-carrier can extend the drug residence time in the stomach, reducing the drug dose and treatment period of H. pylori eradication therapy.
Sujet(s)
Amoxicilline/pharmacologie , Antibactériens/usage thérapeutique , Infections à Helicobacter/traitement médicamenteux , Helicobacter pylori/effets des médicaments et des substances chimiques , Nanoparticules de magnétite/composition chimique , Résines acryliques/composition chimique , Amoxicilline/composition chimique , Amoxicilline/usage thérapeutique , Animaux , Antibactériens/composition chimique , Antibactériens/pharmacologie , Matériaux biocompatibles/composition chimique , Matériaux biocompatibles/métabolisme , Matériaux biocompatibles/pharmacologie , Matériaux biocompatibles/usage thérapeutique , Biofilms/effets des médicaments et des substances chimiques , Lignée cellulaire , Chitosane/composition chimique , Vecteurs de médicaments/composition chimique , Vecteurs de médicaments/métabolisme , Composés du fer III/composition chimique , Muqueuse gastrique/métabolisme , Muqueuse gastrique/anatomopathologie , Infections à Helicobacter/microbiologie , Infections à Helicobacter/médecine vétérinaire , Helicobacter pylori/isolement et purification , Helicobacter pylori/physiologie , Humains , Champs magnétiques , Souris , Souris de lignée BALB C , Facteurs tempsRÉSUMÉ
Aim: Cells with CD133 overexpression, a theoretical cancer stem cells (CSCs) marker, have been shown to induce colorectal cancer (CRC) initiation and relapse. Therefore, the detection and treatment of CSCs are the most important factors in overcoming CRC. Materials & methods: Herein, we developed a magnetite-based nanomedicine (superparamagnetic iron oxide@poly(sodium styrene sulfonate)/irinotecan/human serum albumin-anti-CD133 nanoparticle) using loco-regional hyperthermia combined with chemotherapy for CRC- and CSC-specific targeting treatment. Results: The designed nanoparticles were highly biocompatible and exhibited a higher temperature increase rate under radiofrequency generator irradiation. The nanoparticles could be used as a T2-weighted magnetic resonance imaging contrast media, and also applied during hyperthermia and chemotherapy to display a synergistic anticancer effect. Conclusion: Therefore, the superparamagnetic iron oxide@poly(sodium styrene sulfonate)/irinotecan/human serum albumin-anti-CD133 nanoparticles are a powerful candidate for future antitumor strategies.
Sujet(s)
Hyperthermie provoquée , Nanoparticules de magnétite , Tumeurs , Lignée cellulaire tumorale , Humains , Hyperthermie , Imagerie par résonance magnétique , Magnétisme , NanomédecineRÉSUMÉ
Cancer is a complex and tenacious disease. Drug-delivery systems in combination with multimodal therapy strategies are very promising candidates for cancer theranostic applications. In this study, a new drug-delivery vehicle that combine human serum albumin (HSA)- and poly(sodium 4-styrenesulfonate) (PSS)-coated gold nanorod nanoparticles(GNR/PSS/HSA NPs) was developed for synergistic cancer therapy. Doxorubicin (DOX) was loaded onto GNR/PSS/HSA NPs, by electrostatic and hydrophobic forces, to create multimodal DOX@GNR/PSS/HSA NPs. DOX@GNR/PSS/HSA NPs were found to be highly biocompatible and stable in physiological solutions. Furthermore, GNR/PSS/HSA NPs with or without DOX were designed to exhibit strong absorbance in the near-infrared region and high photothermal conversion efficiency. Therefore, bimodal DOX release from DOX@GNR/PSS/HSA NPs could be triggered by an acidic pH and by near-infrared irradiation after NPs preferentially accumulated at tumor sites, leading to a significant chemotherapeutic effect. Moreover, DOX@GNR/PSS/HSA NPs were designed to be applied during chemo- and photo-thermal combination therapy and exhibited a synergistic anticancer effect that was superior to the effect of monotherapy, from both in vitro and in vivo results. These results suggest that DOX@GNR/PSS/HSA NPs are a strong candidate for a nanoplatform for future antitumor therapeutic strategies.
Sujet(s)
Antibiotiques antinéoplasiques/pharmacologie , Préparations à action retardée , Doxorubicine/pharmacologie , Thérapie moléculaire ciblée/méthodes , Nanotubes/composition chimique , Tumeurs/thérapie , Animaux , Antibiotiques antinéoplasiques/composition chimique , Antibiotiques antinéoplasiques/métabolisme , Association thérapeutique/méthodes , Doxorubicine/composition chimique , Doxorubicine/métabolisme , Préparation de médicament/méthodes , Libération de médicament , Femelle , Or/composition chimique , Cellules HeLa , Humains , Concentration en ions d'hydrogène , Rayons infrarouges , Injections sous-cutanées , Photothérapie de faible intensité/méthodes , Souris , Souris nude , Polymères/composition chimique , Sérum-albumine humaine/composition chimique , Acides sulfoniques/composition chimique , Tests d'activité antitumorale sur modèle de xénogreffeRÉSUMÉ
CD133(+) cells in glioblastoma (GBM) display cancer stem cell-like properties and have been considered as the culprit of tumor recurrence, justifying exploration of potential therapeutic modalities targeting CD133(+) cancer stem-like cells (CSCs). For photothermolysis studies, GBM-CD133(+) and GBM-CD133(-) cells mixed with various ratios were challenged with single-walled carbon nanotubes (SWNTs) conjugated with CD133 monoclonal antibody (anti-CD133) and then irradiated with near-infrared laser light. Results show that GBM-CD133(+) cells were selectively targeted and eradicated, whereas GBM-CD133(-) cells remained viable. In addition, in vitro tumorigenic and self-renewal capability of GBM-CD133(+) treated with localized hyperthermia was significantly blocked. Furthermore, GBM-CD133(+) cells pretreated with anti-CD133-SWNTs and irradiated by near-infrared laser 2 days after xenotransplantation in nude mice did not exhibit sustainability of CSC features for tumor growth. Taken altogether, our studies demonstrated that anti-CD133-SWNTs have the potential to be utilized as a thermal-coupling agent to effectively target and destroy GBM CSCs in vitro and in vivo. FROM THE CLINICAL EDITOR: Glioblastoma remains one of the most notorious cancer from the standpoint of recurrence and overall resistance to therapy. CD133+ stem cells occur among GBM cells, and may be responsible for the huge recurrence risk. This paper discusses a targeted elimination method of these cells, which may enable more efficient therapy in an effort to minimize or prevent recurrence.
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Anticorps monoclonaux/composition chimique , Antigènes CD/immunologie , Glioblastome/thérapie , Glycoprotéines/immunologie , Hyperthermie provoquée/méthodes , Nanotubes de carbone/composition chimique , Cellules souches tumorales/anatomopathologie , Peptides/immunologie , Antigène AC133 , Animaux , Anticorps monoclonaux/immunologie , Humains , Souris , Souris nude , Cellules cancéreuses en cultureRÉSUMÉ
High-risk neuroblastoma is one of the most common deaths in pediatric oncology. Current treatment of this disease involves a coordinated sequence of chemotherapy, surgery, and radiation. Further advances in therapy will require the targeting of tumor cells in a more selective and efficient way so that survival can be improved without substantially increasing toxicity. To achieve tumor-selective delivery, disialoganglioside (GD2) expressed by almost all neuroblastoma tumors represents a potential molecular target that can be exploited for tumor-selective delivery. In this study, GD2 monoclonal antibody (anti-GD2) was conjugated to gold nanorods (GNRs) which are one of anisotropic nanomaterials that can absorb near-infrared (NIR) laser light and convert it to energy for photothermolysis of tumor cells. Thiolated chitosan, due to its biocompatibility, was used to replace cetyltrimethylammonium bromide (CTAB) originally used in the synthesis of gold nanorods. In order to specifically target GD2 overexpressed on the surface of neuroblastoma stNB-V1 cells, anti-GD2 was conjugated to chitosan modified GNRs (CGNRs). To examine the fate of CGNRs conjugated with anti-GD2 after incubation with neuroblastoma cells, rhadoamine B was labeled on CGNRs functionalized with anti-GD2. Our results illustrated that anti-GD2-conjugated CGNRs were extensively endocytosed by GD2+ stNB-V1 neuroblastoma cells via antibody-mediated endocytosis. In addition, we showed that anti-GD2 bound CGNRs were not internalized by GD2- SH-SY5Y neuroblastoma cells. After anti-GD2-linked CGNRs were incubated with neuroblatoma cells for six hours, the treated cells were further irradiated with 808 nm NIR laser. Post-NIR laser exposure, when examined by calcein-AM dye, stNB-V1 cells all underwent necrosis, while non-GD2 expressing SH-SY5Y cells all remained viable. Based on the in vitro study, CGNRs bound with anti-GD2 has the potential to be utilized as a therapeutic thermal coupling agent that generates heat sufficient to selectively kill neuroblastoma cells under NIR laser light exposure.
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A primary intracranial yolk sac tumor (YST) is a type of germ cell tumor (GCT) and usually involves the pineal or suprasellar regions, as do other GCTs. Primary YST in the basal ganglia is not common, and bilateral basal ganglia involvement is even rarer. Early diagnosis is often difficult because of minimal or subtle findings without space-occupying lesions shown on neuroimaging during the early course of the disease. We report a case of primary intracranial YST encountered in the basal ganglia bilaterally and describe the clinical presentation, diagnostic problem, imaging characteristics, histopathologic features, and prognosis of the tumor. To the best of our knowledge, this is only the third reported case of primary YST confined to the basal ganglia in the literature.
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Noyaux gris centraux/anatomopathologie , Tumeurs du cerveau/anatomopathologie , Tumeur du sac vitellin/anatomopathologie , Enfant , Femelle , Humains , Imagerie par résonance magnétique , TomodensitométrieRÉSUMÉ
Development of rapid antiviral assays can expedite the process of screening potential agents against viral pathogens. In the present study, fluorescent quantum dots (QDs) incorporated with infectious pancreatic necrosis virus (IPNV) were used as imaging nanoprobes to detect the threshold amount of poly I:C (an interferon inducer) required to induce zebrafish cells into an antiviral state against IPNV. QD-IPNV hybrids were formed by colloidal clustering of negatively charged QDs and IPNV, using the cationic polymer polybrene (50 µg/mL). To test the screening potential of the QD-IPNV hybrids for anti-IPNV drug candidates, zebrafish ZF4 cells primed with the immunostimulant poly I:C at concentrations of 1, 5, and 10 µg/mL for 6h were used as a model system. After poly I:C treatment, cells were exposed to the QD-IPNV hybrids for 6h at a multiplicity of infection (MOI) of 5. The anti-IPNV effectiveness of poly I:C was assessed via fluorescence intensity of the QDs. Our results showed that ZF4 cells primed with poly I:C at 10 µg/mL were highly protected from IPNV challenge (i.e., no detection of QD fluorescence). In summary, a rapid and efficient cell-based imaging platform has been developed for assessing the anti-IPNV activity of poly I:C on ZF4 cells using QD-IPNV hybrids. This approach may be applied to a wider range of fish species and fish pathogenic viruses.
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Antiviraux/pharmacologie , Traitement d'image par ordinateur/méthodes , Virus de la nécrose pancréatique infectieuse/effets des médicaments et des substances chimiques , Boîtes quantiques , Animaux , Lignée cellulaire , Facteurs immunologiques/pharmacologie , Tests de sensibilité microbienne/méthodes , Poly I-C/pharmacologie , Danio zébréRÉSUMÉ
Quantum dots (QDs) have great potential for applications in bio-related fields, due to their high photoluminescence, photochemical stability and size-dependent emission. QDs used for the construction of QD-virus hybrids can be harnessed as an imaging probe to reveal viral infection pathways and screen antiviral agents. In the study, human embryonic kidney (HEK) 293T cells were transfected with three plasmids, pSIN-EGFP, pMDG, and p8.91, to produce lentiviruses which can make infected cells express enhanced green fluorescent protein (EGFP). The QDs employed were CdSe-ZnS semiconductor nanocrystals emitting red fluorescence. The QD-virus hybrids, constructed as lentiviruses, were budding from the membrane surface of HEK 293T producer cells on which QDs encapsulated with alkylated chitosan (chitosan-QDs) were pre-adsorbed via electrostatic attraction force. Such in situ formation of QD-virus hybrids was confirmed by TEM micrographs indicating the lentivirus was capped with chitosan-modified QDs. To further illustrate the effectiveness (i.e., infectivity and photoluminescence) of the constructed QD-virus hybrids, NIH 3T3 cells were infected with the in situ fabricated QD-virus hybrids. Our results showed QDs were indeed entering NIH 3T3 cells along with lentiviruses as hybrids. Moreover, photoluminescence and infectivity of QD-virus hybrids remained intact, as compared to QDs and lentivirus alone. The unique approach of constructing QD-virus hybrids taking advantage of the viral budding process offers a feasible tool to create enveloped virus incorporated with nanomaterials for the study of fundamental and applied virology.
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Chitosane/composition chimique , Infections à lentivirus/virologie , Lentivirus/physiologie , Boîtes quantiques , Animaux , Humains , Lentivirus/ultrastructure , Souris , Microscopie électronique à transmission , Microscopie de fluorescence , Cellules NIH 3T3RÉSUMÉ
Despite aggressive multimodality therapy, most neuroblastoma-bearing patients relapse and survival rate remains poor. Exploration of alternative therapeutic modalities is needed. Carbon nanotubes (CNTs), revealing optical absorbance in the near-infrared region, warrant their merits in photothermal therapy. In order to specifically target disialoganglioside (GD2) overexpressed on the surface of neuroblastoma stNB-V1 cells, GD2 monoclonal antibody (anti-GD2) was conjugated to acidified CNTs. To examine the fate of anti-GD2 bound CNTs after incubation with stNB-V1 cells, rhodamine B was labeled on carboxylated CNTs functionalized with and without anti-GD2. Our results illustrated that anti-GD2-linked CNTs were extensively internalized by neuroblastoma cells via GD2-mediated endocytosis. In addition, we showed that anti-GD2 bound CNTs were not ingested by PC12 cells without GD2 expression. After anti-GD2 conjugated CNTs were incubated with neuroblastoma cells for 6 h and endocytosed by the cells, CNT-laden neuroblastoma cells were further irradiated with an 808 nm near-infrared (NIR) laser with intensity ramping from 0.6 to 6 W cm(-2) for 10 min which was then maintained at 6 W cm(-2) for an additional 5 min. Post-NIR laser exposure, and after being examined by calcein-AM dye, stNB-V1 cells were all found to undergo necrosis, while non-GD2 expressing PC12 cells all remained viable. Based on the in vitro study, CNTs bound with anti-GD2 have the potential to be utilized as a therapeutic thermal coupling agent that generates heat sufficient to selectively kill neuroblastoma cells under NIR laser light exposure.
Sujet(s)
Anticorps monoclonaux/pharmacologie , Gangliosides/immunologie , Hyperthermie provoquée/méthodes , Immunoconjugués/pharmacologie , Nanotubes de carbone/composition chimique , Neuroblastome/traitement médicamenteux , Animaux , Anticorps monoclonaux/composition chimique , Anticorps monoclonaux/immunologie , Anticorps monoclonaux/pharmacocinétique , Lignée cellulaire tumorale , Survie cellulaire/effets des médicaments et des substances chimiques , Colorants fluorescents/composition chimique , Gangliosides/composition chimique , Humains , Immunoconjugués/composition chimique , Immunoconjugués/pharmacocinétique , Microscopie électronique à transmission , Neuroblastome/métabolisme , Neuroblastome/anatomopathologie , Cellules PC12 , Rats , Rhodamines/composition chimiqueRÉSUMÉ
INTRODUCTION: Rasmussen's encephalitis (RE) is one of the important causes of refractory seizure. The most impressive clinical manifestation of RE is epilepsia partialis continua (EPC). Others include progressive hemiparesis and neuropsychological deterioration. Currently, the best approach to RE is hemispherectomy. CASE HISTORIES: We describe a patient whose clinical manifestations were compatible with RE; however, the initial brain MRI was interpreted as focal cortical dysplasia over right parietal region. DISCUSSION: The follow-up brain MRI 1 year later showed diffuse atrophy of the brain with more atrophic change in right hemisphere, and the EPC disappeared after right hemispherectomy.
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Encéphale/anatomopathologie , Encéphalite/diagnostic , Encéphalite/anatomopathologie , Malformations corticales/diagnostic , Malformations corticales/anatomopathologie , Encéphale/imagerie diagnostique , Encéphale/physiopathologie , Enfant d'âge préscolaire , Diagnostic différentiel , Électroencéphalographie , Encéphalite/physiopathologie , Fluorodésoxyglucose F18 , Humains , Imagerie par résonance magnétique , Mâle , Malformations corticales/physiopathologie , Tomographie par émission de positonsRÉSUMÉ
OBJECTIVE: The salvage therapy of recurrent embryonal brain tumors in children is disappointing. Temozolomide is a newly developed chemotherapeutic agent in central nervous system tumors. This study analyzed the efficacy of temozolomide on the treatment of recurrent embryonal brain tumors in children. MATERIALS AND METHODS: There were eight patients, including four with medulloblastoma (MB), three with atypical teratoid/rhabdoid tumor (AT/RT) and one with supratentorial primitive neuroectodermal tumor, whose tumors recurred after surgery and radiotherapy, with or without conventional intravenous cisplatin-based chemotherapy. They all received once daily oral temozolomide (150 mg/m(2)/day) for five consecutive days in a 28-day cycle. The responsiveness of the tumors to temozolomide was judged by magnetic resonance imaging (MRI) during regular follow-up. RESULTS: The median treatment cycles received by these eight patients were 17 (range from two to 59 cycles). The follow-up MRI showed no tumor progression in five patients at 6 months and four patients at 12 months. The median progression-free survival (PFS) of the eight patients was 15.7 months (range from 0 to 59 months). Complete response was achieved in one patient with MB accompanying with a long period of PFS for 26 months. Another patient with AT/RT showed partial response accompanying with a long period of PFS for 59 months. The observed adverse effects of temozolomide included nausea, vomiting, headache, constipation, mild marrow suppression, and decreased activity; none of them was severe enough to discontinue the treatment. No patient experienced moderate or severe marrow suppression in this series. CONCLUSION: In this preliminary study, oral temozolomide shows promising results on recurrent embryonal brain tumors in children. The adverse effects of temozolomide are mild and tolerable. When conventional chemotherapy fails and/or the adverse response is too severe to tolerate, temozolomide is a reasonable alternative. However, a further well-designed, controlled study and more long-term follow-up are needed to assess the exact role of temozolomide in children with embryonal tumors in brain.
Sujet(s)
Antinéoplasiques alcoylants/usage thérapeutique , Tumeurs du cerveau/traitement médicamenteux , Dacarbazine/analogues et dérivés , Médulloblastome/traitement médicamenteux , Tumeurs neuroectodermiques primitives/traitement médicamenteux , Tumeur rhabdoïde/traitement médicamenteux , Tératome/traitement médicamenteux , Administration par voie orale , Adolescent , Antinéoplasiques alcoylants/administration et posologie , Antinéoplasiques alcoylants/effets indésirables , Dacarbazine/administration et posologie , Dacarbazine/effets indésirables , Dacarbazine/usage thérapeutique , Survie sans rechute , Femelle , Études de suivi , Céphalée/induit chimiquement , Humains , Imagerie par résonance magnétique , Mâle , Médulloblastome/radiothérapie , Médulloblastome/chirurgie , Nausée/induit chimiquement , Tumeurs neuroectodermiques primitives/radiothérapie , Tumeurs neuroectodermiques primitives/chirurgie , Tumeur rhabdoïde/radiothérapie , Tumeur rhabdoïde/chirurgie , Témozolomide , Tératome/radiothérapie , Tératome/chirurgie , Résultat thérapeutique , Vomissement/induit chimiquementRÉSUMÉ
The increasing threats of viral diseases have gained worldwide attention in recent years. Quite a few infectious diseases are still lacking effective prevention or treatment. The pace of developing antiviral agents could be expedited by the availability of quick and efficient drug screening platforms. In this study, quantum dot (QD), an emerging probe for biological imaging and medical diagnostics, was employed to form complexes with virus and used as fluorescent imaging probes for exploring potential antiviral therapeutics. Inorganic CdSe/ZnS QDs synthesized in organic phase were encapsulated by amphiphilic alginate to attain biocompatible water-soluble QDs via phase transfer. Virus employed for this study was dengue virus which is a notorious one in tropical and subtropical regions of the world. To construct a QD-virus imaging modality capable of providing meaningful information, preservation of viral infectivity after tagging virus with QDs is of utmost importance. In order to form colloidal complexes of QD-virus, electrostatic repulsion force generated from both negatively charged virus and QDs was neutralized by various concentrations of cationic polybrene. Results showed that BHK-21 cells infected with dengue viruses incorporated with QDs exhibited bright fluorescence intracellularly within 30 min. To demonstrate the potency of QD-virus complexes as bioprobes for screening antiviral agents, BHK-21 cells were incubated for one hour with allophycocyanin purified from blue-green algae and then infected with QD-virus complexes. Based on the developed cell-based imaging assay, allophycocyanin with concentration of 125 microg/mL led to extremely weak intracellular fluorescence post-infection of QD-virus complexes for 30 min. That is, the efficacy of anti-dengue viral activity of the algae extract was clearly illustrated by the inorganic-organic hybrid platform constructed in current study.
Sujet(s)
Alginates/composition chimique , Matériaux revêtus, biocompatibles/composition chimique , Virus de la dengue/isolement et purification , Virus de la dengue/ultrastructure , Rein/virologie , Microscopie de fluorescence/méthodes , Boîtes quantiques , Tensioactifs/composition chimique , Animaux , Lignée cellulaire , Cricetinae , Acide glucuronique/composition chimique , Acides hexuroniques/composition chimique , Interactions hydrophobes et hydrophilesRÉSUMÉ
Neonatal adrenal hemorrhage presenting as an abdominal mass in the newborn is not uncommon. However, judging the nature of a suprarenal mass is sometimes difficult, especially when the structure is more complex with unusual clinical course. We report a male newborn with neonatal adrenal hemorrhage presenting as a multiloculated cystic mass. The margins between the mass and left kidney were indistinct. All laboratory data including complete blood cell count, serum electrolytes, liver function, renal function, blood sugar, alpha-fetoprotein, beta-human chorionic gonadotropin, urinalysis, and 24-hour urine vanillylmandelic acid were within normal limits. Serial sonographic follow-up revealed failure to decrease in size without change in echogenicity. Surgical exploration was performed to exclude the possibility of malignancy. This case highlights the diagnostic problems that arise when a space-occupying lesion is found near or at the adrenal gland in the neonate. We suggest that early surgical intervention for the suprarenal mass without sufficient evidence of malignancy would not be prudent.