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1.
Int Ophthalmol ; 44(1): 307, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38955894

RESUMEN

PURPOSE: To review long-term outcomes of circumscribed choroidal hemangioma (CCH). METHODS: Hospital charts of all CCH cases diagnosed from 2008 to 2019 were retrospectively reviewed. RESULTS: All 172 patients were managed with either observation, transpupillary thermotherapy, argon laser photocoagulation, photodynamic therapy, plaque brachytherapy or stereotactic radiosurgery. The most common 3 modes of management were clinical observation (30.2%), transpupillary thermotherapy (52.9%) and argon laser photocoagulation (8.7%). Median follow-up time was 10 months (range: 3, 160). Anatomical outcomes were stable in 87.1% of observation group and improved in 60.5% of thermotherapy group. Quantified optical coherence tomography angiography findings showed statistical differences in vascular and perfusion densities in fellow eyes of hemangioma patients. CONCLUSION: Circumscribed choroidal hemangioma can be treated in various ways. Transpupillary thermotherapy is an anatomically effective treatment in selected cases. The diagnosis of CCH may have vascular implications in fellow eyes of the patients.


Asunto(s)
Neoplasias de la Coroides , Angiografía con Fluoresceína , Hemangioma , Centros de Atención Terciaria , Tomografía de Coherencia Óptica , Agudeza Visual , Humanos , Neoplasias de la Coroides/terapia , Neoplasias de la Coroides/diagnóstico , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Tomografía de Coherencia Óptica/métodos , Angiografía con Fluoresceína/métodos , Adulto , Centros de Atención Terciaria/estadística & datos numéricos , Hemangioma/terapia , Hemangioma/diagnóstico , Anciano , Estudios de Seguimiento , Fotoquimioterapia/métodos , Hipertermia Inducida/métodos , Fondo de Ojo , Adulto Joven , Coroides/patología , Coroides/irrigación sanguínea
2.
Nanotheranostics ; 8(4): 442-457, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38961886

RESUMEN

The global incidence of cancer continues to rise, posing a significant public health concern. Although numerous cancer therapies exist, each has limitations and complications. The present study explores alternative cancer treatment approaches, combining hyperthermia and photodynamic therapy (PDT). Magnetic nanoparticles (MNPs) and amine-functionalized carbon quantum dots (A-CQDs) were synthesized separately and then covalently conjugated to form a single nanosystem for combinational therapy (M-CQDs). The successful conjugation was confirmed using zeta potential, Fourier transform infrared spectroscopy (FT-IR), and UV-visible spectroscopy. Morphological examination in transmission electron microscopy (TEM) further verified the conjugation of CQDs with MNPs. Energy dispersive X-ray spectroscopy (EDX) revealed that M-CQDs contain approximately 12 weight percentages of carbon. Hyperthermia studies showed that both MNP and M-CQDs maintain a constant therapeutic temperature at lower frequencies (260.84 kHz) with high specific absorption rates (SAR) of 118.11 and 95.04 W/g, respectively. In vitro studies demonstrated that MNPs, A-CQDs, and M-CQDs are non-toxic, and combinational therapy (PDT + hyperthermia) resulted in significantly lower cell viability (~4%) compared to individual therapies. Similar results were obtained with Hoechst and propidium iodide (PI) staining assays. Hence, the combination therapy of PDT and hyperthermia shows promise as a potential alternative to conventional therapies, and it could be further explored in combination with existing conventional treatments.


Asunto(s)
Carbono , Hipertermia Inducida , Nanopartículas de Magnetita , Neoplasias , Fotoquimioterapia , Puntos Cuánticos , Puntos Cuánticos/química , Fotoquimioterapia/métodos , Humanos , Carbono/química , Hipertermia Inducida/métodos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapéutico , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Supervivencia Celular/efectos de los fármacos , Línea Celular Tumoral , Terapia Combinada , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología
3.
J Gastric Cancer ; 24(3): 246-256, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38960884

RESUMEN

PURPOSE: Peritoneal carcinomatosis (PC) presents a major challenge in the treatment of late-stage, solid tumors, with traditional therapies limited by poor drug penetration. We evaluated a novel hyperthermic pressurized intraperitoneal aerosol chemotherapy (HPIPAC) system using a human abdominal cavity model for its efficacy against AGS gastric cancer cells. MATERIALS AND METHODS: A model simulating the human abdominal cavity and AGS gastric cancer cell line cultured dishes were used to assess the efficacy of the HPIPAC system. Cell viability was measured to evaluate the impact of HPIPAC under 6 different conditions: heat alone, PIPAC with paclitaxel (PTX), PTX alone, normal saline (NS) alone, heat with NS, and HPIPAC with PTX. RESULTS: Results showed a significant reduction in cell viability with HPIPAC combined with PTX, indicating enhanced cytotoxic effects. Immediately after treatment, the average cell viability was 66.6%, which decreased to 49.2% after 48 hours and to a further 19.6% after 120 hours of incubation, demonstrating the sustained efficacy of the treatment. In contrast, control groups exhibited a recovery in cell viability; heat alone showed cell viability increasing from 90.8% to 94.4%, PIPAC with PTX from 82.7% to 89.7%, PTX only from 73.3% to 74.8%, NS only from 90.9% to 98.3%, and heat with NS from 74.4% to 84.7%. CONCLUSIONS: The HPIPAC system with PTX exhibits a promising approach in the treatment of PC in gastric cancer, significantly reducing cell viability. Despite certain limitations, this study highlights the system's potential to enhance treatment outcomes. Future efforts should focus on refining HPIPAC and validating its effectiveness in clinical settings.


Asunto(s)
Aerosoles , Supervivencia Celular , Quimioterapia Intraperitoneal Hipertérmica , Paclitaxel , Neoplasias Peritoneales , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/terapia , Paclitaxel/farmacología , Paclitaxel/administración & dosificación , Quimioterapia Intraperitoneal Hipertérmica/métodos , Supervivencia Celular/efectos de los fármacos , Línea Celular Tumoral , Hipertermia Inducida/métodos , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/farmacología
5.
World J Surg Oncol ; 22(1): 171, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926860

RESUMEN

INTRODUCTION: The safety and efficacy of CRS + HIPEC combined with urinary tract resection and reconstruction are controversial. This study aims to summarize the clinicopathological features and to evaluate the safety and survival prognosis of CRS + HIPEC combined with urinary tract resection and reconstruction. METHODS: The patients who underwent urinary tract resection and reconstruction as part of CRS surgery were retrospectively selected from our disease-specific database for analysis. The clinicopathological characteristics, treatment-related variables, perioperative adverse events (AEs), and survival outcomes were studied using a descriptive approach and the K-M analysis with log-rank comparison. RESULTS: Forty-nine patients were enrolled. Perioperative serious AEs (SAEs) were observed in 11 patients (22.4%), with urinary SAEs occurring in 3 patients (6.1%). Additionally, there were 23 cases (46.8%) involving urinary adverse events (UAEs). The median overall survival (OS) in the entire cohort was 59.2 (95%CI: 42.1-76.4) months. The median OS of the UAE group and No-UAE group were 59.2 months (95%CI not reached), and 50.5 (95%CI: 11.5 to 89.6) months, respectively, with no significant difference (P = 0.475). Furthermore, there were no significant differences in OS based on the grade of UAEs or the number of UAEs (P = 0.562 and P = 0.622, respectively). CONCLUSION: The combination of CRS + HIPEC with urinary tract resection and reconstruction is associated with a high incidence of Grade I-II UAEs, which do not have an impact on OS. The safety profile of this combined technique is acceptable. However, this is a retrospective single-center single-arm analysis, with limitations of generalizability and potential selection bias. The findings need high-level validation.


Asunto(s)
Procedimientos Quirúrgicos de Citorreducción , Hipertermia Inducida , Quimioterapia Intraperitoneal Hipertérmica , Humanos , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Pronóstico , Anciano , Hipertermia Inducida/métodos , Hipertermia Inducida/efectos adversos , Hipertermia Inducida/mortalidad , Quimioterapia Intraperitoneal Hipertérmica/métodos , Estudios de Seguimiento , Adulto , Procedimientos Quirúrgicos de Citorreducción/métodos , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Procedimientos Quirúrgicos de Citorreducción/mortalidad , Terapia Combinada , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/mortalidad , Neoplasias Peritoneales/patología , Sistema Urinario/cirugía , Sistema Urinario/patología , Procedimientos Quirúrgicos Urológicos/métodos , Procedimientos de Cirugía Plástica/métodos , Complicaciones Posoperatorias/etiología
6.
Drug Dev Ind Pharm ; 50(6): 561-575, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38832870

RESUMEN

INTRODUCTION: Breast cancer (BC) is the most common malignancy in women globally. Significant progress has been made in developing structural nanoparticles (NPs) and formulations for targeted smart drug delivery (SDD) of pharmaceuticals, improving the precision of tumor cell targeting in therapy. SIGNIFICANCE: Magnetic hyperthermia (MHT) treatment using magneto-liposomes (MLs) has emerged as a promising adjuvant cancer therapy. METHODS: CoFe2O4 magnetic NPs (MNPs) were conjugated with nanoliposomes to form MLs, and the anticancer drug quercetin (Que) was loaded into MLs, forming Que-MLs composites for antitumor approach. The aim was to prepare Que-MLs for DD systems (DDS) under an alternating magnetic field (AMF), termed chemotherapy/hyperthermia (chemo-HT) techniques. The encapsulation efficiency (EE), drug loading capacity (DL), and drug release (DR) of Que and Que-MLs were evaluated. RESULTS: The results confirmed successful Que-loading on the surface of MLs, with an average diameter of 38 nm and efficient encapsulation into MLs (69%). In vitro, experimental results on MCF-7 breast cells using MHT showed high cytotoxic effects of novel Que-MLs on MCF-7 cells. Various analyses, including cytotoxicity, apoptosis, cell migration, western blotting, fluorescence imaging, and cell membrane internalization, were conducted. The Acridine Orange-ethidium bromide double fluorescence test identified 35% early and 55% late apoptosis resulting from Que-MLs under the chemo-HT group. TEM results indicated MCF-7 cell membrane internalization and digestion of Que-MLs, suggesting the presence of early endosome-like vesicles on the cytoplasmic periphery. CONCLUSIONS: Que-MLs exhibited multi-modal chemo-HT effects, displaying high toxicity against MCF-7 BC cells and showing promise as a potent cytotoxic agent for BC chemotherapy.


Asunto(s)
Apoptosis , Neoplasias de la Mama , Daño del ADN , Hipertermia Inducida , Liposomas , Quercetina , Humanos , Quercetina/farmacología , Quercetina/administración & dosificación , Quercetina/química , Células MCF-7 , Apoptosis/efectos de los fármacos , Hipertermia Inducida/métodos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Daño del ADN/efectos de los fármacos , Cobalto/química , Cobalto/administración & dosificación , Cobalto/farmacología , Femenino , Compuestos Férricos/química , Liberación de Fármacos , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas de Magnetita/química , Supervivencia Celular/efectos de los fármacos , Campos Magnéticos
7.
In Vivo ; 38(4): 1665-1670, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38936909

RESUMEN

BACKGROUND/AIM: Hyperthermia represents an adjuvant local anticancer strategy which relies on the increase of temperature beyond the physiological level. In this study, we investigated the anticancer potential of Fe3O4 and Fe3O4core Aushell nanoparticles as hyperthermic agents in terms of cytotoxicity and studied the expression of cellular markers of proliferation (changes in mRNA levels via real-time polymerase chain reaction). MATERIALS AND METHODS: The human breast cancer cell line SK-BR-1 was incubated with either Fe3O4 or Fe3O4core Aushell nanoparticles stabilized with tryptophan, prior to hyperthermia treatment. The normal HEK293 cell line was used as a control. Toxicity was determined using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay to estimate possible toxic effects of the tested nanoparticles. After RNA extraction and cDNA synthesis, mRNA expression of three indicators of proliferation, namely marker of proliferation Ki-67, DNA topoisomerase II alpha (TOP2A) and TPX2 microtubule nucleation factor (TPX2), was investigated. RESULTS: At each concentration tested, Fe3O4core Aushell nanoparticles showed greater toxicity compared to Fe3O4, while SK-BR-3 cells were more susceptible to their cytotoxic effects compared to the HEK293 cell line. The expression of Ki-67, TOP2A and TPX2 was reduced in SK-BR-3 cells by both Fe3O4 or Fe3O4core Aushell nanoparticles compared to untreated cells, while the only observed change in HEK293 cells was the up-regulation of TOP2A. CONCLUSION: Both Fe3O4core Aushell and Fe3O4 NPs exhibit increased cytotoxicity to the cancer cell line tested (SK-BR-3) compared to HEK293 cells. The down-regulation in SK-BR-3 cells of the three proliferative markers studied, Ki-67, TOP2A and TPX2, after incubation with NPs suggests that cells that survived thermal destruction were not actively proliferating.


Asunto(s)
Neoplasias de la Mama , Proteínas de Ciclo Celular , Proliferación Celular , ADN-Topoisomerasas de Tipo II , Hipertermia Inducida , Antígeno Ki-67 , Proteínas Asociadas a Microtúbulos , Proteínas de Unión a Poli-ADP-Ribosa , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , ADN-Topoisomerasas de Tipo II/metabolismo , ADN-Topoisomerasas de Tipo II/genética , Proliferación Celular/efectos de los fármacos , Hipertermia Inducida/métodos , Antígeno Ki-67/metabolismo , Antígeno Ki-67/genética , Línea Celular Tumoral , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Femenino , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Unión a Poli-ADP-Ribosa/genética , Proteínas de Unión a Poli-ADP-Ribosa/metabolismo , Células HEK293 , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética
8.
J Colloid Interface Sci ; 672: 724-735, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-38870763

RESUMEN

The integration of functional nanomaterials with tissue engineering scaffolds has emerged as a promising solution for simultaneously treating malignant bone tumors and repairing resected bone defects. However, achieving a uniform bioactive interface on 3D-printing polymer scaffolds with minimized microstructural heterogeneity remains a challenge. In this study, we report a facile metal-coordination self-assembly strategy for the surface engineering of 3D-printed polycaprolactone (PCL) scaffolds with nanostructured two-dimensional conjugated metal-organic frameworks (cMOFs) consisting of Cu ions and 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP). A tunable thickness of Cu-HHTP cMOF on PCL scaffolds was achieved via the alternative deposition of metal ions and HHTP. The resulting composite PCL@Cu-HHTP scaffolds not only demonstrated potent photothermal conversion capability for efficient OS ablation but also promoted the bone repair process by virtue of their cell-friendly hydrophilic interfaces. Therefore, the cMOF-engineered dual-functional 3D-printing scaffolds show promising potential for treating bone tumors by offering sequential anti-tumor effects and bone regeneration capabilities. This work also presents a new avenue for the interface engineering of bioactive scaffolds to meet multifaceted demands in osteosarcoma-related bone defects.


Asunto(s)
Neoplasias Óseas , Regeneración Ósea , Osteosarcoma , Poliésteres , Impresión Tridimensional , Andamios del Tejido , Osteosarcoma/patología , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/terapia , Regeneración Ósea/efectos de los fármacos , Andamios del Tejido/química , Neoplasias Óseas/patología , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/terapia , Poliésteres/química , Humanos , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Estructuras Metalorgánicas/síntesis química , Propiedades de Superficie , Cobre/química , Cobre/farmacología , Hipertermia Inducida , Ingeniería de Tejidos , Tamaño de la Partícula , Catálisis , Animales , Antineoplásicos/farmacología , Antineoplásicos/química , Ratones , Supervivencia Celular/efectos de los fármacos , Nanoestructuras/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos
9.
Nanoscale ; 16(26): 12635-12649, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38884523

RESUMEN

Hyperthermia is considered a promising strategy to boost the curative outcome of traditional chemotherapeutic treatments. However, this thermally mediated drug delivery is still affected by important limitations. First, the poor accumulation of the conventional anticancer formulations in the target site limits the bioavailability of the active ingredient and induces off-site effects. In addition, some tumoral scenarios, such as ovarian carcinoma, are characterized by cell thermotolerance, which induces tumoral cells to activate self-protecting mechanisms against high temperatures. To overcome these constraints, we developed thermoresponsive nanoparticles (NPs) with an upper critical solution temperature (UCST) to intracellularly deliver a therapeutic payload and release it on demand through hyperthermia stimulation. These NPs were synthesized via reversible addition-fragmentation chain transfer (RAFT) emulsion polymerization and combine polyzwitterionic stabilizing segments and an oligoester-based biodegradable core. By leveraging the pseudo-living nature of RAFT polymerization, important physicochemical properties of the NPs were controlled and optimized, including their cloud point (Tcp) and size. We have tuned the Tcp of NPs to match the therapeutic needs of hyperthermia treatments at 43 °C and tested the nanocarriers in the controlled delivery of paclitaxel, a common anticancer drug. The NPs released almost entirely the encapsulated drug only following 1 h incubation at 43 °C, whereas they retained more than 95% of the payload in the physiological environment (37 °C), thus demonstrating their efficacy as on-demand drug delivery systems. The administration of drug-loaded NPs to ovarian cancer cells led to therapeutic effects outperforming the conventional administration of non-encapsulated paclitaxel, which highlights the potential of the zwitterionic UCST-type NPs as an innovative hyperthermia-responsive drug delivery system.


Asunto(s)
Hipertermia Inducida , Nanopartículas , Paclitaxel , Humanos , Paclitaxel/química , Paclitaxel/farmacología , Nanopartículas/química , Línea Celular Tumoral , Femenino , Portadores de Fármacos/química , Supervivencia Celular/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Antineoplásicos/química , Antineoplásicos/farmacología , Neoplasias Ováricas/terapia , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/tratamiento farmacológico
10.
ACS Biomater Sci Eng ; 10(7): 4269-4278, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38916153

RESUMEN

This study investigates the remarkable attributes of sulfur-doped carbon nanodots (CDs) synthesized in high yield and a narrow size distribution (4.8 nm). These CDs exhibit notable features, including potential bioelimination through renal clearance and efficient photothermal conversion in the near-infrared region with multicolor photoluminescence across the visible spectrum. Our research demonstrates high biocompatibility and effective near-infrared (NIR)-triggered photothermal toxicity when targeting mammospheres and patient-derived tumor organoids. Moreover, the study delves into the intricate cellular responses induced by CD-mediated hyperthermia. This involves efficient tumor mass death, activation of the p38-mitogen-activated protein kinase (MAPK) pathway, and upregulation of genes associated with apoptosis, hypoxia, and autophagy. The interaction of CDs with mammospheres reveals their ability to penetrate the complex microenvironment, impeded at 4 °C, indicating an energy-dependent endocytosis mechanism. This observation underscores the CDs' potential for targeted drug delivery, particularly in anticancer therapeutics. This investigation contributes to understanding the multifunctional properties of sulfur-doped CDs and highlights their promising applications in cancer therapeutics. Utilizing 3-D tumor-in-a-dish patients' organoids enhances translational potential, providing a clinically relevant platform for assessing therapeutic efficacy in a context mirroring the physiological conditions of cancerous tissues.


Asunto(s)
Neoplasias de la Mama , Carbono , Nanomedicina Teranóstica , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Carbono/química , Carbono/uso terapéutico , Femenino , Fototerapia/métodos , Puntos Cuánticos/uso terapéutico , Puntos Cuánticos/química , Nanopartículas/química , Nanopartículas/uso terapéutico , Línea Celular Tumoral , Hipertermia Inducida/métodos , Animales
11.
Molecules ; 29(11)2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38893510

RESUMEN

Cancer cells have higher heat sensitivity compared to normal cells; therefore, hyperthermia is a promising approach for cancer therapy because of its ability to selectively kill cancer cells by heating them. However, the specific and rapid heating of tumor tissues remains challenging. This study investigated the potential of magnetic nanoparticles (MNPs) modified with tumor-homing peptides (THPs), specifically PL1 and PL3, for tumor-specific magnetic hyperthermia therapy. The synthesis of THP-modified MNPs involved the attachment of PL1 and PL3 peptides to the surface of the MNPs, which facilitated enhanced tumor cell binding and internalization. Cell specificity studies revealed an increased uptake of PL1- and PL3-MNPs by tumor cells compared to unmodified MNPs, indicating their potential for targeted delivery. In vitro hyperthermia experiments demonstrated the efficacy of PL3-MNPs in inducing tumor cell death when exposed to an alternating magnetic field (AMF). Even without exposure to an AMF, an additional ferroptotic pathway was suggested to be mediated by the nanoparticles. Thus, this study suggests that THP-modified MNPs, particularly PL3-MNPs, hold promise as a targeted approach for tumor-specific magnetic hyperthermia therapy.


Asunto(s)
Hipertermia Inducida , Nanopartículas de Magnetita , Péptidos , Hipertermia Inducida/métodos , Humanos , Nanopartículas de Magnetita/química , Péptidos/química , Péptidos/farmacología , Línea Celular Tumoral , Neoplasias/terapia , Neoplasias/patología , Campos Magnéticos
12.
ACS Appl Mater Interfaces ; 16(24): 30671-30684, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38843203

RESUMEN

Indoleamine 2,3-dioxygenase (IDO), highly expressed in hepatocellular carcinoma (HCC), plays a pivotal role in creating an immune-suppressive tumor microenvironment. Inhibiting IDO activity has emerged as a promising immunotherapeutic strategy; however, the delivery of IDO inhibitors to the tumor site is constrained, limiting their therapeutic efficacy. In this study, we developed a magnetic vortex nanodelivery system for the targeted delivery of the IDO inhibitor NLG919, integrated with magnetic hyperthermia therapy to reverse the immune-suppressive microenvironment of liver cancer and inhibit tumor growth. This system comprises thermoresponsive polyethylenimine-coated ferrimagnetic vortex-domain iron oxide nanorings (PI-FVIOs) loaded with NLG919 (NLG919/PI-FVIOs). Under thermal effects, NLG919 can be precisely released from the delivery system, counteracting IDO-mediated immune suppression and synergizing with NLG919/PI-FVIOs-mediated magnetothermodynamic (MTD) therapy-induced immunogenic cell death (ICD), resulting in effective HCC suppression. In vivo studies demonstrate that this combination therapy significantly inhibits tumor growth and metastasis by enhancing the accumulation of cytotoxic T lymphocytes and suppressing regulatory T cells within the tumor. Overall, our findings reveal that NLG919/PI-FVIOs can induce a potent antitumor immune response by disrupting the IDO pathway and activating the ICD, offering a promising therapeutic avenue for HCC treatment.


Asunto(s)
Indolamina-Pirrol 2,3,-Dioxigenasa , Neoplasias Hepáticas , Microambiente Tumoral , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenasa/antagonistas & inhibidores , Animales , Microambiente Tumoral/efectos de los fármacos , Ratones , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/inmunología , Hipertermia Inducida , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/tratamiento farmacológico , Línea Celular Tumoral , Ratones Endogámicos BALB C , Antineoplásicos/química , Antineoplásicos/farmacología , Imidazoles , Isoindoles
13.
Int J Hyperthermia ; 41(1): 2365385, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38897584

RESUMEN

INTRODUCTION: Pelvic recurrences from rectal cancer present a challenging clinical scenario. Hyperthermia represents an innovative treatment option in combination with concurrent chemoradiation to enhance therapeutic effect. We provide the initial results of a prospective single center feasibility study (NCT02528175) for patients undergoing rectal cancer retreatment using concurrent chemoradiation and mild hyperthermia with MR-guided high intensity focused ultrasound (MR-HIFU). METHODS: All patients were deemed ineligible for salvage surgery and were evaluated in a multidisciplinary fashion with a surgical oncologist, radiation oncologist and medical oncologist. Radiation was delivered to a dose of 30.6 Gy in 1.8 Gy per fraction with concurrent capecitabine. MR-HIFU was delivered on days 1, 8 and 15 of concurrent chemoradiation. Our primary objective was feasibility and toxicity. RESULTS: Six patients (total 11 screened) were treated with concurrent chemoradiation and mild hyperthermia with MR-HIFU. Tumor size varied between 3.1-16.6 cm. Patients spent an average of 228 min in the MRI suite and sonication with the external transducer lasted an average of 35 min. There were no complications on the day of the MR-HIFU procedure and all acute toxicities (no grade >/=3 toxicities) resolved after completion of treatment. There were no late grade >/=3 toxicities. CONCLUSION: Mild hyperthermia with MR-HIFU, in combination with concurrent chemoradiation for appropriately selected patients, is safe for localized pelvic recurrences from rectal cancer. The potential for MR-HIFU to be applied in the recurrent setting in rectal cancer treatment requires further technical development and prospective evaluation.


Asunto(s)
Quimioradioterapia , Hipertermia Inducida , Neoplasias del Recto , Terapia Recuperativa , Humanos , Neoplasias del Recto/terapia , Neoplasias del Recto/diagnóstico por imagen , Masculino , Terapia Recuperativa/métodos , Persona de Mediana Edad , Femenino , Hipertermia Inducida/métodos , Quimioradioterapia/métodos , Anciano , Imagen por Resonancia Magnética/métodos , Recurrencia Local de Neoplasia/terapia , Recurrencia Local de Neoplasia/diagnóstico por imagen , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Estudios Prospectivos , Adulto
14.
Urol Pract ; 11(4): 727-734, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38899675

RESUMEN

INTRODUCTION: Water vapor thermal therapy (WVTT) is a minimally invasive therapy designed to treat lower urinary tract symptoms associated with benign prostatic hyperplasia. Long-term outcomes with large (>80 cc) and small (<30 cc) prostate volumes (PVs) remain limited. We report 48-month outcomes for a multiethnic cohort of WVTT-treated men, stratified by PV. METHODS: In this single-center retrospective study, patients were stratified by PV: < 30 cc, 30 to 80 cc, or > 80 cc. Outcome measures, including International Prostate Symptom Score, quality of life, International Index of Erectile Function, medication usage, and adverse events, were analyzed at baseline and at 1-, 3-, 6-, 12-, 24-, 36-, and/or 48-month follow-up. RESULTS: Two hundred fifty-two patients met inclusion; 35 (13.9%) had PVs < 30 cc, 196 (77.8%) had PVs 30 to 80 cc, and 21 (8.3%) had PVs > 80 cc. Most patients were Asian (33.7%) or non-Hispanic Black (29.4%). International Prostate Symptom Score and quality of life improved in all cohorts from baseline at all follow-ups (all P < .05), with no differences between cohorts. International Index of Erectile Function-Orgasmic Function and -Erectile Function domains improved in 30 to 80 cc patients at 48 months. Alpha blocker and/or 5-alpha reductase inhibitor usage decreased at all follow-ups in < 30 cc and 30 to 80 cc patients and remained durable to only 6 months for > 80 cc patients. No significant differences in adverse events or reoperation rates were observed between cohorts. CONCLUSIONS: Our study suggests WVTT to be efficacious, durable, and safe in managing lower urinary tract symptoms across PVs, although PV > 80 cc patients may require benign prostatic hyperplasia medication at long-term follow-up. Further research is desired to clarify WVTT's role regarding sexual function and in treating men with larger PVs.


Asunto(s)
Próstata , Hiperplasia Prostática , Vapor , Humanos , Masculino , Hiperplasia Prostática/terapia , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Resultado del Tratamiento , Próstata/patología , Tamaño de los Órganos , Síntomas del Sistema Urinario Inferior/terapia , Calidad de Vida , Factores de Tiempo , Hipertermia Inducida/métodos
15.
Int J Nanomedicine ; 19: 5227-5243, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38855734

RESUMEN

Purpose: This study aimed to construct targeting drug-loading nanocomposites (FA-FePt/DDP nanoliposomes) to explore their potential in ovarian cancer therapy and molecular magnetic resonance imaging (MMRI). Methods: FA-FePt-NPs were prepared by coupling folate (FA) with polyethylene-glycol (PEG)-coated ferroplatinum nanoparticles and characterized. Then cisplatin (DDP) was encapsulated in FA-FePt-NPs to synthesize FA-PEG-FePt/DDP nanoliposomes by thin film-ultrasonic method and high-speed stirring, of which MMRI potential, magnetothermal effect, and the other involved performance were analyzed. The therapeutic effect of FA-FePt/DDP nanoliposomes combined with magnetic fluid hyperthermia (MFH) on ovarian cancer in vitro and in vivo was evaluated. The expression levels of Bax and epithelial-mesenchymal transition related proteins were detected. The biosafety was also preliminarily observed. Results: The average diameter of FA-FePt-NPs was about 30 nm, FA-FePt/DDP nanoliposomes were about 70 nm in hydrated particle size, with drug slow-release and good cell-specific targeted uptake. In an alternating magnetic field (AMF), FA-FePt/DDP nanoliposomes could rapidly reach the ideal tumor hyperthermia temperature (42~44 °C). MRI scan showed that FA-FePt-NPs and FA-FePt/DDP nanoliposomes both could suppress the T2 signal, indicating a good potential for MMRI. The in vitro and in vivo experiments showed that FA-FePt/DDP-NPs in AMF could effectively inhibit the growth of ovarian cancer by inhibiting cancer cell proliferation, invasion, and migration, and inducing cancer cell apoptosis, much better than that of the other individual therapies; molecularly, E-cadherin and Bax proteins in ovarian cancer cells and tissues were significantly increased, while N-cadherin, Vimentin, and Bcl-2 proteins were inhibited, effectively inhibiting the malignant progression of ovarian cancer. In addition, no significant pathological injury and dysfunction was observed in major visceras. Conclusion: We successfully synthesized FA-FePt/DDP nanoliposomes and confirmed their good thermochemotherapeutic effect in AMF and MMRI potential on ovarian cancer, with no obvious side effects, providing a favorable strategy of integrated targeting therapy and diagnosis for ovarian cancer.


Asunto(s)
Antineoplásicos , Cisplatino , Ácido Fólico , Liposomas , Imagen por Resonancia Magnética , Neoplasias Ováricas , Polietilenglicoles , Femenino , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/terapia , Liposomas/química , Cisplatino/farmacología , Cisplatino/química , Cisplatino/administración & dosificación , Cisplatino/farmacocinética , Animales , Ácido Fólico/química , Ácido Fólico/farmacología , Ácido Fólico/farmacocinética , Humanos , Imagen por Resonancia Magnética/métodos , Polietilenglicoles/química , Línea Celular Tumoral , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Ratones , Platino (Metal)/química , Platino (Metal)/farmacología , Hipertermia Inducida/métodos , Nanocompuestos/química , Ratones Desnudos , Ratones Endogámicos BALB C , Nanopartículas del Metal/química , Campos Magnéticos , Tamaño de la Partícula
16.
Lasers Med Sci ; 39(1): 150, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38836959

RESUMEN

PURPOSE: To investigate the swept-source optical coherence tomography (SS-OCT) and SS-OCT angiography (SS-OCTA) findings in circumscribed choroidal hemangioma (CCH) before and after treatment with transpupillary thermotherapy (TTT). METHODS: The clinical records of 21 eyes having CCH imaged with SS-OCT/SS-OCTA between September 2018 and December 2022 were evaluated. RESULTS: SS-OCT examination in CCH showed dome-shaped appearance (100%), choroidal shadowing (100%), expansion of choroidal structures (100%), subretinal fluid (66.7%), intraretinal edema/schisis (33.3%), retinal pigment epithelium (RPE) atrophy (19.0%), hyperreflective dots (19.0%), and epiretinal membrane (4.8%). Internal arborizing tumor vessels showing hyperreflectivity were observed in the choriocapillaris slab on SS-OCTA in all eyes. In the deep capillary plexus (DCP), flow void changes were seen in 7 eyes with intraretinal schisis/cystoid macular edema. Four CCHs > 2 mm in thickness showed outer retinal involvement due to unmasking of flow in intratumoral vessels related to RPE atrophy. Following TTT/indocyanine green-enhanced TTT (ICG-TTT) of CCH, SS-OCT findings included total/partial resolution of subretinal fluid (57.1%), complete/partial regression of the tumor (52.4%), and RPE atrophy (33.3%). After treatment; loss of choriocapillaris, decrease in tumor vascularity together with increase in the fibrous component and flow void areas were detected on SS-OCTA. CONCLUSIONS: SS-OCT/SS-OCTA are useful non-invasive tools for imaging the structural/vascular changes in CCHs managed with TTT or ICG-TTT. On SS-OCTA, hyporeflective spaces localizing to edema/schisis in the DCP and arborizing tumor vessels within a hyporeflective stromal background in the choriocapillaris slab were observed. After TTT/ICG-TTT, a decrease in tumor vessels and an increase in the fibrous component and flow-void areas inside the CCH were detected on SS-OCTA.


Asunto(s)
Neoplasias de la Coroides , Hemangioma , Hipertermia Inducida , Tomografía de Coherencia Óptica , Humanos , Tomografía de Coherencia Óptica/métodos , Neoplasias de la Coroides/terapia , Neoplasias de la Coroides/diagnóstico por imagen , Neoplasias de la Coroides/patología , Femenino , Persona de Mediana Edad , Masculino , Hemangioma/terapia , Hemangioma/diagnóstico por imagen , Hemangioma/patología , Adulto , Hipertermia Inducida/métodos , Anciano , Angiografía con Fluoresceína/métodos , Estudios Retrospectivos , Coroides/diagnóstico por imagen , Coroides/irrigación sanguínea , Coroides/patología
17.
World J Urol ; 42(1): 383, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38904777

RESUMEN

PURPOSE: To investigate safety and feasibility of performing water vapor thermal therapy (WVTT; Rezum, Boston Scientific, Marlborough, MA, USA) without postoperative catheterization among men with benign prostatic hyperplasia. METHODS: This is a prospective, single arm, unblinded pilot study of 20 consecutive male patients ages 40-80 who underwent WVTT at a single academic institution. All patients underwent 1 injection per lobe at the point of maximal obstruction based on visualization. Primary outcome was evaluation of voiding parameters, symptom scores, and need for catheterization at 3 day, 1, 3, and 6 month follow up compared to baseline visit 30 days prior to surgery. RESULTS: Mean age was 65 years (range 55-75). Mean prostate volume and PVR were 43 cc (range 30-68) and 89 cc, with 30% (n = 6) having median lobes. Patients received 2-3 treatments based on presence of bilobar versus trilobar hyperplasia. One patient (55 cc prostate, no median lobe) required catheterization for acute urinary retention on postoperative day 2. No patients required antibiotics for urinary tract infection or inpatient readmission within 30 days. Qmax significantly increased from 6 mL/s to 8, 13, 12, and 14 at 3 days, 1, 3, and 6 months (p < 0.05). IPSS decreased from 17 preoperatively to 10, 6, 7, and 8 (p < 0.05). No significant differences were noted in PVR, IIEF, MSHQ-EjD, or SF-12. CONCLUSIONS: In well-selected men, catheter-free WVTT is feasible and improved voiding parameters and symptom scores. No changes in sexual function, infectious complications, or readmission were noted. Only 1 patient (5%) required postoperative catheterization within 30 days.


Asunto(s)
Estudios de Factibilidad , Hiperplasia Prostática , Vapor , Humanos , Masculino , Hiperplasia Prostática/terapia , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Proyectos Piloto , Resultado del Tratamiento , Anciano de 80 o más Años , Adulto , Hipertermia Inducida/métodos
19.
Anticancer Res ; 44(7): 3043-3050, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38925817

RESUMEN

BACKGROUND/AIM: This study evaluated the feasibility and safety of whole-body hyperthermia pressurized intraperitoneal aerosol chemotherapy (WBH-PIPAC) in patients with peritoneal surface malignancies. PATIENTS AND METHODS: This study retrospectively analyzed a database of 28 patients who had received one cycle of normothermic PIPAC prior to repetitive WBH-PIPACs. WBH (39-40°C) was induced using a Water-filtered infrared A device. Doxorubicin plus cisplatin or oxaliplatin was nebulized into a constant capnoperitoneum of 20 mmHg for 30 min at doses of 6.0 mg, 30.0 mg, or 120 mg per m2 body surface area, respectively. The primary outcome measures were feasibility and perioperative complications. RESULTS: The median age was 62 years (range=45-78 years). Primary tumor sites included the upper gastrointestinal tract (n=9), colon/rectum (n=7), hepato-pancreato-biliary system (n=3), peritoneum (n=2), ovaries (n=2), and unknown primary (n=5). The induction of WBH failed in one patient (6 liters ascites). After a median warming period of 95 min (53-117 min), the median rectal temperature (Trec) was 39.5°C (39.2-39.9°C). No hyperthermia-related side effects were observed. Twenty-seven patients received 50 WBH-PIPACs. The median time of therapeutic capnoperitoneum and treatment time with Trec ≥39°C was 39 min (37-43 min) and 66 min (53-69 min), respectively. The overall rate of postoperative procedure-related complications was 9/50, including seven grade I and two grade II complications. There were no grade III-V complications. CONCLUSION: In a highly selected group of patients, the feasibility and perioperative safety of WBH-PIPAC was comparable to normothermic PIPAC.


Asunto(s)
Aerosoles , Estudios de Factibilidad , Neoplasias Peritoneales , Humanos , Persona de Mediana Edad , Femenino , Anciano , Masculino , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/terapia , Estudios Retrospectivos , Hipertermia Inducida/métodos , Hipertermia Inducida/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Quimioterapia Intraperitoneal Hipertérmica/métodos , Quimioterapia Intraperitoneal Hipertérmica/efectos adversos , Oxaliplatino/administración & dosificación , Oxaliplatino/efectos adversos , Oxaliplatino/uso terapéutico
20.
Int J Mol Sci ; 25(12)2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38928434

RESUMEN

Although the moderate thermal stimulation of articular cartilage exerts chondroprotective effects, it is difficult to effectively heat deep articular cartilage with conventional methods. Photosensitizers increase the ambient temperature using near-infrared (NIR) radiation, which has high tissue permeability. We hypothesized that the intra-articular administration of photosensitizers and NIR irradiation would exert a greater heating effect on articular cartilage. We aimed to evaluate the heating effect of this method on cultured chondrocytes and rat knee cartilage. In vitro, we irradiated a photosensitizer-containing medium with NIR and measured changes in the medium temperature, cytotoxicity, and gene expression of heat shock protein (HSP) 70 and aggrecan (ACAN). In vivo, the knee joints of rats treated with photosensitizers were irradiated with NIR, and changes in intra-articular temperature and gene expression were measured, alongside histological analysis. The results showed that the medium and intra-articular temperature were raised to approximately 40 °C with no apparent disruption to articular cartilage or the immunohistochemically enhanced staining of HSP70 in chondrocytes. The gene expression of HSP70 and ACAN was increased in both cultured and articular cartilage. In summary, this method can safely heat joints and enhance cartilage metabolism by inducing HSP70 expression in articular cartilage. It presents a new hyperthermia therapy with effective cartilage protection.


Asunto(s)
Cartílago Articular , Condrocitos , Proteínas HSP70 de Choque Térmico , Fármacos Fotosensibilizantes , Animales , Ratas , Cartílago Articular/metabolismo , Condrocitos/metabolismo , Fármacos Fotosensibilizantes/farmacología , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas HSP70 de Choque Térmico/genética , Agrecanos/metabolismo , Agrecanos/genética , Masculino , Células Cultivadas , Ratas Sprague-Dawley , Rayos Infrarrojos , Hipertermia Inducida/métodos
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