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Immunosuppression tumor microenvironment (TME) seriously impedes anti-tumor immune response, resulting in poor immunotherapy effect of cancer. This study develops a folate-modified delivery system to transport the plasmids encoding immune stimulatory chemokine CKb11 and PD-L1 inhibitors to tumor cells, resulting in high CKb11 secretion from tumor cells, successfully activating immune cells and increasing cytokine secretion to reshape the TME, and ultimately delaying tumor progression. The chemokine CKb11 enhances the effectiveness of tumor immunotherapy by increasing the infiltration of immune cells in TME. It can cause high expression of IFN-γ, which is a double-edged sword that inhibits tumor growth while causing an increase in the expression of PD-L1 on tumor cells. Therefore, combining CKb11 with PD-L1 inhibitors can counterbalance the suppressive impact of PD-L1 on anti-cancer defense, leading to a collaborative anti-tumor outcome. Thus, utilizing nanotechnology to achieve targeted delivery of immune stimulatory chemokines and immune checkpoint inhibitors to tumor sites, thereby reshaping immunosuppressive TME for cancer treatment, has great potential as an immunogene therapy in clinical applications.
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Bromodomain-Containing Protein 4 (BRD4) is a member of the BET family of bromodomains, which participates in gene transcription process and is closely related to tumor progression. We observed the up-regulated expression of BRD4 in colorectal cancer (CRC) after doxorubicin (DOX) treatment, which might be a potential mechanism for DOX resistance. This study constructed the tumor-targeting (cyclo (Arg-Gly-Asp-D-Phe-Lys)-poly(ethylene glycol)-poly(ε-caprolactone)) (cRGD-PEG-PCL) copolymer for co-delivery of DOX and BRD4 PROTAC degrader ARV-825 (ARV-DOX/cRGD-P) for CRC treatment. The ARV-DOX/cRGD-P complexes elicited synergistic anti-tumor effect via cell cycle arrest and the increased cell apoptosis, and mechanism studies implicated the regulation of proliferation- and apoptosis-related pathways in vitro. Moreover, the administration of ARV-DOX/cRGD-P significantly improved anti-tumor activity in subcutaneous colorectal tumors and colorectal intraperitoneal disseminated tumor models in mice by promoting tumor apoptosis, suppressing tumor proliferation and angiogenesis. Taken together, these data reveal that ARV-825 can heighten DOX sensitivity in CRC treatment and BRD4 is a potential therapeutic target for DOX-resistant CRC. The ARV-DOX/cRGD-P preparations have outstanding anti-cancer effects and may be used for clinical treatment of colorectal cancer in the future.
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Neoplasias Colorrectales , Nanopartículas , Animales , Ratones , Proteínas Nucleares , Línea Celular Tumoral , Quimera Dirigida a la Proteólisis , Proteolisis , Factores de Transcripción/metabolismo , Doxorrubicina/farmacología , Antibióticos Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológicoRESUMEN
Swine acute diarrhea syndrome coronavirus (SADS-CoV) is an enveloped, positive single-stranded RNA virus belonging to Coronaviridae family, Orthocoronavirinae subfamily, Alphacoronavirus genus. As one of the main causes of swine diarrhea, SADS-CoV has brought huge losses to the pig industry. Although we have a basic understanding of SADS-CoV, the research on the pathogenicity and interactions between host and virus are still limited, especially the metabolic changes induced by SADS-CoV infection. Here, we utilized a combination of untargeted metabolomics and lipomics to analyze the metabolic alteration in SADS-CoV infected cells. Significant changes were observed in 1257 of 2225 metabolites identified in untargeted metabolomics, while the number of lipomics was 435 out of 868. Metabolic pathway enrichment analysis showed that amino acid metabolism, tricarboxylic acid (TCA) cycle and ferroptosis were disrupted during viral infection, suggesting that these metabolic pathways may partake in pathological processes related to SADS-CoV pathogenesis. Collectively, our findings gain insights into the cellular metabolic disorder during SADS-CoV infection, offer a valuable resource for further exploration of the relationship between virus and host metabolic activities, and provide potential targets for the development of antiviral drugs.
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Alphacoronavirus , Infecciones por Coronavirus , Enfermedades de los Porcinos , Porcinos , Animales , Infecciones por Coronavirus/veterinaria , Alphacoronavirus/genética , Diarrea/veterinaria , Células EpitelialesRESUMEN
Current treatment of glioma is hampered due to the physical blood-brain barrier (BBB) and the resistance to traditional chemotherapeutic agents. Herein, we proposed a combined treatment strategy based on Cyclo (Arg-Gly-Asp-d-Phe-Lys) (cRGDfk) peptides-modified nanoparticle named cRGD-P in a self-assembly method for the co-delivery of doxorubicin (DOX) and BRD4 PROTAC degrader ARV-825 (ARV). Molecular dynamics simulations showed that cRGD-P could change its conformation to provide interaction sites for perfectly co-loading DOX and ARV. The cRGD-P/ARV-DOX exhibited an average size of 39.95 ânm and a zeta potential of -0.25 âmV. Increased expression of BRD4 in glioma cells was observed after being stimulated by cRGD-P/DOX, confirming one of the possible mechanisms of DOX resistance and the synergistic tumor inhibition effect of BRD4 degrading ARV combined with DOX. In the study, the combination of DOX and ARV in the cRGD-P nanoparticle system exhibited synergistic suppression of tumor growth in glioma cells on account of cell cycle arrest in the G2/M phase and the activation of tumor cells apoptosis-related pathways including triggering caspase cascade and downregulating Bcl-2 as well as upregulating Bax. The cRGD-P/ARV-DOX system could effectively suppress the heterotopic and orthotopic growth of glioma by increasing tumor apoptosis, inhibiting tumor proliferation, and decreasing tumor angiogenesis in vivo. Therefore, the cRGD-modified nanoparticle to co-deliver DOX and ARV provides a potential platform for exploiting a more effective and safer combination therapy for glioma.
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Porcine parvovirus (PPV) infection is the primary cause of SMEDI (stillbirth; mummification; embryonic death; infertility) syndrome, which is a global burden for the swine industry. Thus, it is crucial to establish a rapid and efficient detection method against PPV infection. In the present work, we developed a recombinase-aided amplification (RAA) assay, coupled with a lateral flow dipstick (LFD), to achieve an amplification of PPV DNA at 37 °C within 15 min. The detection limits of PPV RAA-LFD assay were 102 copies/µL recombinant plasmid pMD19-T-VP1, 6.38 × 10-7 ng/µL PPV DNA, and 10-1 TCID50/mL virus, respectively. This method was highly specific for PPV detection with no cross-reactivity for other swine pathogens. In contrast to polymerase chain reaction (PCR), the PPV RAA-LFD assay is more sensitive and cost-saving. Hence, the established PPV RAA-LFD assay provided an alternative for PPV detection, especially in resource-limited regions.
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Pre-mRNA processing factor 19 (PRPF19) is a multifaceted protein and participates in DNA damage response and pre-mRNA processing. The role of PRPF19 in cancer is unclear. Here, we report that the expression of PRPF19 in human tongue cancer is associated with unfavorable prognosis. Overexpression of PRPF19 promotes while knockdown of PRPF19 inhibits tongue cancer cell migration, proliferation, and tumor growth. Overexpression of PRPF19 increases the resistance of tongue cancer cells to radiation and cisplatin treatment. Furthermore, PRPF19 regulates the expression of solute carrier family 40 member 1 (SLC40A1) and mono-ADP ribosylhydrolase 2 (MACROD2), knockdown of SLC40A1 or MACROD2 decreases the sensitivity of tongue cancer cells to radiation and cisplatin treatment. Thus, our results establish a key role of PRPF19 in tongue cancer growth and chemoradiotherapy resistance, targeting PRPF19 would be an effective therapeutic strategy for tongue cancer, especially for those resistant to chemoradiotherapy.
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Movimiento Celular , Proliferación Celular , Quimioradioterapia , Cisplatino/farmacología , Enzimas Reparadoras del ADN/metabolismo , Resistencia a Antineoplásicos , Proteínas Nucleares/metabolismo , Factores de Empalme de ARN/metabolismo , Tolerancia a Radiación , Neoplasias de la Lengua , Animales , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/efectos de la radiación , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Enzimas Reparadoras del ADN/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de la radiación , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/genética , Factores de Empalme de ARN/genética , Tolerancia a Radiación/efectos de los fármacos , Tolerancia a Radiación/efectos de la radiación , Radiación Ionizante , Neoplasias de la Lengua/genética , Neoplasias de la Lengua/metabolismo , Neoplasias de la Lengua/patología , Neoplasias de la Lengua/terapia , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Background: Esthesioneuroblastoma (ENB) is a rare sinonasal malignancy, lacking a unified staging system and treatment. Management at a single center was retrospectively evaluated to inform future treatment options and prognostic factors. Methods: Clinical data of 64 consecutive ENB patients, including prognostic factors and treatment methods, were reviewed retrospectively. Data were collected to calculate overall survival (OS) and progression free survival (PFS). Results: The majority of tumors 84.4% were within Kadish C stage, 79.7% were within T3 or T4, and 64.0% were within Hyams grade III or IV. A total of 50 (78.1%) patients received surgery and combined radiotherapy with or without chemotherapy, 10 (15.6%) received surgery with or without chemotherapy alone, and 4 (6.3%) received radiotherapy with or without chemotherapy alone. The majority of patients (79.7%) underwent endoscopic resection (endoscopic and endoscopically assisted). Surgery combined with radiotherapy with or without chemotherapy resulted in significantly better OS (84.4 vs. 50.6%, 84.4 vs. 37.5%) compared to surgery alone and radiotherapy alone (P = 0.0064). Endoscopic surgery group (endoscopic and endoscopically assisted) resulted in significantly better 5-year PFS (61.7 vs. 22.2%) compared to the open surgery group (P < 0.001). Although endoscopic surgery group was not a statistically significant predictor of 5-year OS (P = 0.54), the 5-year OS was 79.3% for the endoscopic surgery group and 76.2% for the open surgery group. A Cox regression analysis identified intracranial extension and surgery combined with radiotherapy as independent factors affecting 5-year OS while cervical lymph node metastasis and Hyams grade IV as independent factors affecting 5-year PFS. Conclusion: Our findings suggest that surgery combined with radiotherapy is the best treatment approach for ENB. For advanced tumors, endoscopic surgery is an effective treatment, and its survival rate is equal to or better than open surgery.
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Erythropoietin-producing hepatocellular receptor A2 (EphA2) receptor tyrosine kinase plays an important role in tissue organization and homeostasis in normal organs. EphA2 is overexpressed in a variety of types of solid tumours with oncogenic functions. However, the role of EphA2 in cervical cancer (CC) is still needed to be further explored. Here, we examined the role of EphA2 by establishing a stable EphA2 knock-down CC cell lines or a stable EphA2-overexpressed CC cells lines. Overexpression of EphA2 increased cell proliferation and migration of CC while EphA2 knock-down decreased the CC tumorigenicity. In addition, EphA2 knock-down suppressed CC tumour development in the xenograft mouse model. Inhibition of EphA2 by AWL-II-41-27, EphA2-specific tyrosine kinase inhibitor, or knock-down of EphA2 decreased mRNA and protein expression of cyclin-dependent kinase (CDK) 6 in CC cells, which increased cellular susceptibility to epirubicin (EPI), an anti-cancer chemotherapy drug. A clinicopathological study of EphA2 was conducted on a cohort of 158 human CC patients. EphA2 protein expression was positively correlated with CDK6 protein expression, invasion depth, lymph node metastasis and clinicopathological stage (P < .05). This study demonstrates the oncogenic activity of EphA2 in vitro and in vivo, which provides insights into the relevant mechanisms that might lead to novel treatments for CC.
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Transformación Celular Neoplásica/genética , Quinasa 6 Dependiente de la Ciclina/genética , Regulación Neoplásica de la Expresión Génica , Receptor EphA2/genética , Neoplasias del Cuello Uterino/etiología , Neoplasias del Cuello Uterino/metabolismo , Adulto , Anciano , Animales , Línea Celular Tumoral , Transformación Celular Neoplásica/metabolismo , Quinasa 6 Dependiente de la Ciclina/metabolismo , Modelos Animales de Enfermedad , Resistencia a Antineoplásicos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Xenoinjertos , Humanos , Ratones , Persona de Mediana Edad , Clasificación del Tumor , Receptor EphA2/metabolismo , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patologíaRESUMEN
Two of the biggest hurdles in the deployment of chemotherapeutics against glioma is a poor drug concentration at the tumor site and serious side effects to normal tissues. Nanocarriers delivering different drugs are considered to be one of the most promising alternatives. In this study, a dual delivery system (methoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL)) loaded with α-mangostin (α-m) and doxorubicin (Dox) was decorated and constructed by self-assembly to determine its ability to treat glioma. Molecular dynamics simulations showed that MPEG-PCL could provide ideal interaction positions for both α-m and Dox, indicating that the two drugs could be loaded into MPEG-PCL. Based on the in vitro results, MPEG-PCL loaded with α-m and Dox (α-m-Dox/M) with a size of 25.68 nm and a potential of -1.51 mV was demonstrated to significantly inhibit the growth and promote apoptosis in Gl261, C6 and U87 cells, and the effects of the combination were better than each compound alone. The mechanisms involved in the suppression of glioma cell growth were blockage of the cell cycle in S phase by inhibition of CDK2/cyclin E1 and promotion of apoptosis through the Bcl-2/Bax pathway. The synergetic effects of α-m-Dox/M effectively inhibited tumor growth and prolonged survival time without toxicity in mouse glioma models by inducing glioma apoptosis, inhibiting glioma proliferation and limiting tumor angiogenesis. In conclusion, a codelivery system was synthesized to deliver α-m and Dox to the glioma, thereby suppressing the development of glioma by the mechanisms of cell cycle arrest and cellular apoptosis, which demonstrated the potential of this system to improve the chemotherapy response of glioma.
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Puntos de Control del Ciclo Celular/efectos de los fármacos , Doxorrubicina/uso terapéutico , Glioma/tratamiento farmacológico , Xantonas/uso terapéutico , Animales , Apoptosis , Doxorrubicina/farmacología , Glioma/patología , Humanos , Ratones , Ratones Desnudos , Modelos Moleculares , Xantonas/farmacologíaRESUMEN
[This corrects the article DOI: 10.18632/oncotarget.23507.].
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In recent decades, cancer immunotherapy has demonstrated considerable clinical advantages in cancer therapy. Particularly, the use of immunological gene therapy continues to grow in this field. Macrophage Inflammatory Protein 3 Beta (MIP-3ß) has emerged as a potential immunomodulator for anti-cancer treatments by enhancing the interaction among immune responses. In this study, we demonstrate an innovative targeted gene delivery system based on a self-assembly technique with 1,2-Dioleoyl-3-trimethylammonium-propane (DOTAP), Methoxy poly(ethylene glycol)-poly(lactide) (MPEG-PLA), and folic acid modified poly(ethylene glycol)-poly(ε-caprolactone) (FA-PEG-PCL) (FDMCA). Results showed that the expression of MIP-3ß was up-regulated in cancer cells following the transfection with FDMCA-pMIP-3ß, in comparison with cells transfected with DMCA-pMIP-3ß. The supernatants collected from cancer cells transfected with FDMCA-pMIP-3ß and DMCA-pMIP-3ß both instigate dendritic cell maturation, M1 polarisation of macrophages, activation and presentation of cytotoxicity in lymphocytes. Moreover, tumor growth and metastasis were markedly inhibited following the administration of the FDMCA-pMIP-3ß complex in both subcutaneous and pulmonary metastasis mice models, which is attributed to reduced angiogenesis, enhanced cancer cell apoptosis, and suppressed proliferation by activation of the immune system. Our study suggests that the MIP-3ß plasmid and FDMCA complex provide a new approach for the treatment of breast cancer.
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Nanopartículas , Neoplasias , Animales , Línea Celular Tumoral , Quimiocina CCL19 , Células Dendríticas , Macrófagos , Ratones , Plásmidos , Poliésteres , PolietilenglicolesRESUMEN
INTRODUCTION: Curcumin (Cur) is a natural extract of Asian spice Curcumin longa, showing multi-targeting capability and low toxicity in anti-tumor activities. The low bioavailability restricts its application as a therapeutic agent. Folate (FA) receptors are highly expressed in many malignant tumors while low expressed in normal tissue. Herein, we developed a self-assembled FA modified MPEG-PCL micelle to incorporate Cur (FA/Nano-Cur) and applied it for colorectal cancer therapy. METHODS: We prepared FA/Nano-Cur micelles and identified their characteristics. The drug release behavior, pharmacokinetics and in vitro anti-tumor activities of FA/Nano-Cur were studied. Furthermore, the in vivo anti-tumor ability assessment and anti-tumor mechanisms investigation were carried out in murine colorectal cancer model. RESULTS: FA/Nano-Cur micelles had an average particle size of 30.47 nm. Elongated T1/2 and larger AUC were found in FA/Nano-Cur group than that in the Free Cur group. MTT assay and apoptotic study indicated the growth inhibitory effect and pro-apoptotic effect of FA/Nano-Cur were the most significant among all treatments. Moreover, the in vivo study demonstrated that FA/Nano-Cur micelles exhibited a much stronger effect to suppress tumor growth, promote tumor apoptosis and attenuate tumor angiogenesis than Free Cur and Nano-Cur micelles. CONCLUSION: The present study demonstrated FA/Nano-Cur micelles might be a promising therapeutic agent in colorectal cancer treatment with distinctive advantages of improved bioavailability, sustained drug release, tumor-targeted delivery and low toxicity.
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Antineoplásicos Fitogénicos/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Curcumina/administración & dosificación , Animales , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Disponibilidad Biológica , Línea Celular Tumoral , Curcumina/farmacología , Preparaciones de Acción Retardada/farmacología , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Femenino , Ácido Fólico/química , Ratones Endogámicos BALB C , Micelas , Nanoestructuras/administración & dosificación , Nanoestructuras/química , Tamaño de la Partícula , Poliésteres/química , Polietilenglicoles/química , RatasRESUMEN
Targeted drug delivery systems have currently demonstrated considerable potential clinical benefits in cancer treatment. Curcumin has become a candidate anti-tumor drug for the therapy of glioblastoma multiforme (GBM) by increasing cell apoptosis and suppressing cell proliferation. In current research, we explored a novel targeted drug delivery system with a self-assembly measure by curcumin, MPEG-PLA and Fa-PEG-PLA. Compared with free curcumin and Cur/MPEG-PLA, Cur/Fa-PEG-PLA can remarkably suppress the growth of GL261 cells and promote apoptotic rate. Moreover, after the procession of tumor-bearing mice with curcumin/Fa-PEG-PLA complex, tumor growth in subcutaneous and intracranial tumor models were repressed via suppressing angiogenesis and facilitating apoptosis in vivo. The Curcumin/Fa-PEG-PLA nanoparticle may be a novel drug for the therapy of GBM.
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Curcumina , Glioma , Animales , Antineoplásicos , Línea Celular Tumoral , Portadores de Fármacos , Ácido Fólico , Ratones , Micelas , PolietilenglicolesRESUMEN
α-Mangostin (αM), a traditional natural product with promising application of treating a series of diseases, was limited use in clinical due to its hydrophobicity. Herein, MPEG-PCL nanomicelles were used to embed the αM for resolving hydrophobicity and improving the anti-melanoma effect of the αM. The anti-melanoma activity and potential mechanisms of biodegradable αM/MPEG-PCL nanomicelles were investigated. The αM/MPEG-PCL nanomicelles possessed a stronger effect on anti-melanoma compared to the free αM both in vitro and in vivo with a low cytotoxicity in non-tumor cell lines. In the research of mechanisms, the αM/MPEG-PCL nanomicelles inhibited the proliferation of melanoma cell, induced apoptosis via both apoptosis pathways of intrinsic and exogenous in vitro, as well as suppressed tumor growth and restrained angiogenesis in vivo, which implied that the αM/MPEG-PCL nanomicelles have potential application as a novel chemotherapeutic agent in melanoma therapy.
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Antineoplásicos/uso terapéutico , Sistemas de Liberación de Medicamentos/métodos , Melanoma/tratamiento farmacológico , Micelas , Nanopartículas/química , Neoplasias Cutáneas/tratamiento farmacológico , Xantonas/uso terapéutico , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Poliésteres/química , Polietilenglicoles/química , Ratas , Ratas Sprague-Dawley , Xantonas/administración & dosificación , Xantonas/químicaRESUMEN
Colorectal cancer is one of the most common and malignant cancer in the world wide. Recently, combination of target therapy and chemotherapy has generated new promise for colorectal cancer. Apatinib mesylate is a novel and highly selective VEGFR-2 inhibitor, presented with an outstanding activity of anti-angiogensis, which has the potential for treating various tumors. As a traditional chemotherapeutic drug, docetaxel (Taxotere) is a widely used semisynthetic taxoid in solid tumors. In this study, Liposome and Methoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) were constructed as drug delivery system for the delivery of apatinib (Lipo-Apa) and docetaxel (DOC/M), respectively. Co-administration of Lipo-Apa and DOC/M showed synergistically effects on inhibiting cell proliferation and inducing cell apoptosis of CT26 cells in vitro. Moreover, fibrin glue, as a biocompatible adherent hemostat, was used as a kind of vehicle for locally delivery of DOC/M in animal models, for achieving locally high concentration and prolonging releasing time. Combination of Lipo-Apa by gavage and locally delivery of DOC/M showed significantly improved anti-tumor activity in a subcutaneous xenograft model as well as in the abdominal metastasis model of colorectal cancer. In addition, promoted tumor apoptosis, inhibited proliferation and decreased tumor angiogenesis were presented by the co-administration. Finally, our study suggested that combination of oral administration of Lipo-Apa and locally delivery of DOC/M by fibrin glue, has the potential to be applied clinically in colorectal cancer therapy.
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Neoplasias Colorrectales , Liposomas , Administración Oral , Animales , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Docetaxel , Adhesivo de Tejido de Fibrina , Poliésteres , Polietilenglicoles , PiridinasRESUMEN
Colorectal cancer (CRC) exhibited high incidence rate worldwide and the advanced CRC had a poor prognosis. Thereupon, seeking efficient treatment for CRC is critical. Apatinib is a novel vascular epithelial growth factor receptor (VEGFR) inhibitor with inspiring therapeutic effect in some malignant cancers. In our study, doxorubicin was mixed in fibrin gel and apatinib was encapsulated with self-synthesized liposome. The results showed liposomal apatinib (Lipo-Apatinib) could enhance the intracellular uptake of doxorubicin in vitro. Moreover, compared with doxorubicin loaded fibrin gel (DOX-FG) alone, the combination of DOX-FG and Lipo-Apatinib significantly improved the anti-tumor effect in mice CRC subcutaneous model and abdominal metastasis model Drug combination successfully inhibited tumor angiogenesis and tumor proliferation, and also promoted tumor apoptosis. Our data suggested that combined therapy of DOX-FG and Lipo-Apatinib would be a promising treatment approach for CRC.
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Antineoplásicos/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Doxorrubicina/administración & dosificación , Fibrina/administración & dosificación , Piridinas/administración & dosificación , Animales , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Neoplasias Colorrectales/patología , Doxorrubicina/química , Combinación de Medicamentos , Liberación de Fármacos , Femenino , Fibrina/química , Geles , Liposomas , Ratones Endogámicos BALB C , Piridinas/química , Resultado del TratamientoRESUMEN
AIM: This retrospective study is aimed at investigating whether aldosterone-renin ratio (ARR) cutoffs calculated by the plasma aldosterone concentration (PAC)/plasma renin concentration (PRC) should be set differently in patients of different ages. METHODS: 521 hypertensive patients were screened for primary aldosteronism (PA) by the PAC/PRC. 174 patients diagnosed with PA and 311 patients with essential hypertension (EH) were included in the final analysis. Subjects were subdivided into four age groups: <40, 40-49, 50-59, and ≥60 years old. RESULTS: The accuracy of the ARR varied greatly among the different age groups. An ARR of 3.7 (ng/dl)/(µIU/ml) had a sensitivity of 100% and a specificity of 80% in patients ≥ 60 years old. With this cutoff, the sensitivities in patients < 40, 40-49, and 50-59 years old were 74%, 82%, and 87%, respectively, and the specificities were 94%, 95%, and 94%, respectively. To achieve a sensitivity higher than 90%, the ARR cutoff needed to be lowered to 2.0 (ng/dl)/(µIU/ml) for patients 40-49 and 50-59 years old, resulting in sensitivities of 90% and 95%, respectively, and specificities of 80% and 84%, respectively. To achieve a sensitivity higher than 90%, the ARR cutoff needed to be lowered to 1.0 (ng/dl)/(µIU/ml) for patients < 40 years old, resulting in a sensitivity of 90% and a specificity of 82%. CONCLUSIONS: An ARR of 3.7 (ng/dl)/(µIU/ml) is optimal for patients ≥ 60 years; for patients 40-59 years, the optimal ARR cutoff is 2.0; for those younger than 40 years, an ARR of 1.0 may be more reasonable.
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Colorectal cancer is very common worldwide and advanced colorectal cancer exhibited very poor clinical outcome. Oxaliplatin (OXP) is one of the principal chemotherapeutic agents in colorectal cancer treatment presenting impressive anti-tumor ability, limited by adverse effect in clinical practice. Fibrin glue (FG) is a biocompatible formulation made of fibrinogen and thrombin, extensively used in surgery for hemostasis, tissue adhesion and sealing. In this study, FG was innovatively applied as OXP delivery system and results showed enhanced anti-tumor performance in subcutaneous model and abdominal metastasis model of murine colorectal cancer compared with that of OXP used alone. It is revealed that combination of OXP and FG could increase activated CD8+ T cells, reduce regulatory T (Treg) cells and increase interferon-γ (IFN-γ). Furthermore, results showed promoted tumor apoptosis, decreased proliferation and inhibited tumor angiogenesis by OXP and FG combination. No obvious systemic toxicity was observed in this study. Finally, our findings provided basis for promising application of OXP and FG combination in colorectal cancer treatment.
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OBJECTIVE: This study was undertaken to demonstrate that gastrointestinal mucosal injury occurs during cardiopulmonary bypass in children, increasing systemic inflammatory responses, and to determine whether shen-fu injection (the major components of which are ginsenosides compound, extract of Panax ginseng shown to have antioxidant properties) could attenuate gastrointestinal mucosal injury and subsequent inflammatory responses. METHODS: Twenty-four children undergoing heart surgery for congenital heart defects were randomly assigned to groups C (placebo control, n = 12) and G (1.35 mg/kg ginsenosides compound intravenously before and throughout the course of cardiopulmonary bypass, n = 12). Central venous blood samples were taken before cardiopulmonary bypass and at 60 and 120 minutes after aortic declamping (reperfusion). Gastric intramucosal pH was measured by perioperative tonometry. Plasma lipid peroxidation product malondialdehyde, myocardium-specific creatine kinase isoenzyme MB activity, diamine oxidase, lipopolysaccharide, and interleukin 6 were all measured. RESULTS: Significant decrease in gastric intramucosal pH and increase in plasma diamine oxidase were seen during reperfusion in group C, accompanied by increases in plasma levels of malondialdehyde, lipopolysaccharide, interleukin 6, and creatine kinase isoenzyme MB (P < .01 vs before cardiopulmonary bypass). Shen-fu injection significantly attenuated these changes (P < .05). Consequently, fewer patients in group G (2/12) than in group C (7/12) needed postoperative inotropic support. Postoperative intensive care unit stay was shorter in group G than in group C. A tight positive correlation was seen between diamine oxidase and interleukin 6 at 60 minutes after aortic declamping and between diamine oxidase and lipopolysaccharide at 120 minutes after aortic declamping (r = 0.79, P < .0001). CONCLUSION: Ginsenosides compound may attenuate gastrointestinal injury and inhibit inflammatory response after cardiopulmonary bypass in patients with congenital heart disease.