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Metilasas de Modificación del ADN , Enzimas Reparadoras del ADN , Resistencia a Antineoplásicos , Glioblastoma , Células Madre Neoplásicas , Temozolomida , Regulación hacia Arriba , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patología , Temozolomida/uso terapéutico , Temozolomida/farmacología , Humanos , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Metilasas de Modificación del ADN/metabolismo , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Enzimas Reparadoras del ADN/metabolismo , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Regulación hacia Arriba/efectos de los fármacos , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Antineoplásicos Alquilantes/uso terapéutico , Antineoplásicos Alquilantes/farmacologíaRESUMEN
PURPOSE: This study aimed to assess metabolic changes to monitor the progression from normal liver to hepatitis B virus (HBV)-related hepatitis and liver fibrosis using hyperpolarized 13C magnetic resonance imaging (MRI). PROCEDURES: Hepatitis was induced in mice (n = 16) via hydrodynamic injection of HBV 1.2 plasmid (25 µg). Among them, liver fibrosis was induced in the mice (n = 8) through weight-adapted administration of thioacetamide with ethanol. Normal control mice (n = 8) were injected with a phosphate buffer solution. Subsequently, a hyperpolarized 13C MRI was performed on the mouse liver in vivo. The level of hepatitis B surface antigen (HBsAg) in blood serum was measured. Statistical analysis involved comparing the differential metabolite ratios, blood biochemistry values, and body weight among the three groups using the Kruskal-Wallis one-way analysis of variance. RESULTS: HBsAg was absent in the normal and fibrosis groups, while it was detected in the hepatitis group. The ratios of [1-13C] lactate/pyruvate, [1-13C] alanine/pyruvate, [1-13C] lactate/total carbon, and [1-13C] alanine/total carbon were significantly lower in the normal control group than in the hepatitis and fibrosis groups (p < 0.05). Moreover, these ratios were significantly higher in the fibrosis group than in the hepatitis group (p < 0.05). However, no significant differences were observed in either [1-13C] pyruvate-hydrate/pyruvate or [1-13C] pyruvate-hydrate/total carbon among the three groups. CONCLUSIONS: The levels of [1-13C] lactate and [1-13C] alanine in vivo may serve as valuable indicators for differentiating between HBV-related hepatitis, liver fibrosis, and normal liver.
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Progresión de la Enfermedad , Virus de la Hepatitis B , Cirrosis Hepática , Imagen por Resonancia Magnética , Animales , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/virología , Cirrosis Hepática/patología , Cirrosis Hepática/metabolismo , Imagen por Resonancia Magnética/métodos , Hepatitis B/complicaciones , Hepatitis B/diagnóstico por imagen , Masculino , Ratones , Hígado/metabolismo , Hígado/diagnóstico por imagen , Hígado/patología , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/metabolismo , Isótopos de CarbonoRESUMEN
Background. The aim of the study was to synthesize liposomal nanoparticles loaded with temozolomide and ferucarbotran (LTF) and to evaluate the theranostic effect of LTF in the glioma model. Methods. We synthesized an LTF that could pass through the Blood Brain Barrier (BBB) and localize in brain tumor tissue with the help of magnet guidance. We examined the chemical characteristics. Cellular uptake and cytotoxicity studies were conducted in vitro. A biodistribution and tumor inhibition study was conduted using an in vivo glioma model. Results. The particle size and surface charge of LTF show 108 nm and -38 mV, respectively. Additionally, the presence of ferucarbotran significantly increased the contrast agent effect of glioma compared to the control group in MR imaging. Magnet-guided LTF significantly reduced the tumor size compared to control and other groups. Furthermore, compared to the control group, our results demonstrate a significant inhibition in brain tumor size and an increase in lifespan. Conclusions. These findings suggest that the LTF with magnetic guidance represents a novel approach to address current obstacles, such as BBB penetration of nanoparticles and drug resistance. Magnet-guided LTF is able to enhance therapeutic efficacy in mouse brain glioma.
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There is insufficient evidence on the effect of nanoparticles, particularly liposomes loaded with a statin, on acute ischemic stroke. We investigated the impact of atorvastatin-loaded PEG (polyethylene glycol) conjugated liposomes (LipoStatin) on the outcomes in rats with cerebral ischemia-reperfusion. PEGylated liposome loaded with atorvastatin was developed as a nanoparticle to specifically accumulate in an ischemic region and release the drug to ameliorate the harmful effects of the stroke. LipoStatin was administered to rats with transient middle cerebral artery occlusion through the tail vein immediately after reperfusion (LipoStatin group). LipoStatin efficiently accumulated at the cerebral ischemic injury site of the rat. The LipoStatin group showed a significantly reduced infarct volume (p < 0.01) in brain micro-MR imaging and improved neurological function recovery compared to the control group (p < 0.05). In addition, markedly improved brain metabolism using fluorine-18 fluorodeoxyglucose micro-PET/CT imaging was demonstrated in the LipoStatin group compared with the control group (p < 0.01). Mechanistically, as a result of evaluation through IL-1 beta, TNF-alpha, ICAM-1, and Iba-1 mRNA expression levels at 5 days after cerebral ischemia, LipoStatin showed significant anti-inflammatory effects. Protein expression of occludin, JAM-A, Caveolin-1, and eNOS by western blot at 3 days and fluorescent images at 7 days showed considerable recovery of blood-brain barrier breakdown and endothelial dysfunction. PEGylated LipoStatin can be more effectively delivered to the ischemic brain and may have significant neuroprotective effects. Thus, PEGylated LipoStatin can be further developed as a promising targeted therapy for ischemic stroke and other major vascular diseases.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Ratas , Animales , Atorvastatina/uso terapéutico , Liposomas/uso terapéutico , Tomografía Computarizada por Tomografía de Emisión de Positrones , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/tratamiento farmacológico , Polietilenglicoles/uso terapéuticoRESUMEN
BACKGROUND: In this study, we aimed to compare the long-term therapeutic outcomes of drug-eluting bead transarterial chemoembolization (DEB-TACE) with those of radiofrequency ablation (RFA) for the initial treatment of a single small (≤ 3 cm) hepatocellular carcinoma (HCC). METHODS: From January 2010 to December 2021, 259 consecutive patients who underwent DEB-TACE (67 patients) or RFA (192 patients) as a first-line treatment for a single small HCC were enrolled in this retrospective study. The therapeutic outcomes, including cumulative intrahepatic local tumor progression (LTP), progression-free survival (PFS), and long-term overall survival (OS) rates, were compared between the two groups before and after propensity score (PS) matching. Multivariate Cox proportional hazard models were used to evaluate the prognostic factors and differences in OS and PFS between the two groups for all 92 patients after PS matching. RESULTS: After PS matching, the 1-, 2-, 3-, and 5-year LTP rates were lower in the RFA group than those in the DEB-TACE group (P < 0.001), and the 1-, 2-, 3-, and 5-year PFS rates in the RFA group were higher than those in the DEB-TACE group (P = 0.007). However, the 1-, 2-, 3-, and 5-year OS rates were not significantly different between the RFA and DEB-TACE groups (P = 0.584). Moreover, the OS was not significantly different between the RFA and DEB-TACE groups in the univariate and multivariate analyses, with a hazard ratio (HR) of 0.81. The PFS was significantly higher in the RFA group than that in the DEB-TACE group in the univariate analyses, with a HR of 0.44 (P = 0.009). Multivariate Cox regression analysis showed that albumin (P = 0.019) was an independent prognostic factor for OS. Additionally, the major complication rates were not significantly different between the DEB-TACE and RFA groups (P = 1.000). CONCLUSION: The LTP and PFS rates of RFA were superior to those of DEB-TACE in the initial treatment of single small HCC after PS matching. However, the OS rates were not significantly different between RFA and DEB-TACE. Therefore, DEB-TACE may be considered an efficient substitute for RFA in some patients with a single small HCC who are ineligible for RFA.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Ablación por Radiofrecuencia , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Radiation therapy (RT) is a mainstream clinical approach in cancer treatment. However, the therapeutic efficacy of RT is greatly hindered by the presence of excessive hydrogen peroxide (H2O2) in the hypoxic region of the solid tumor, thus leading to tumor recurrence and metastasis. Herein, a thioketal-linked amphiphilic nano-assembly (MTS) loaded with hydrophobic manganese oxide (HMO) nanoparticles (MTS@HMO) is examined as a promising multi-purpose reactive oxygen species (ROS)-catalytic nanozyme for transforming an RT-resistant hypoxic tumor microenvironment (TME) into an RT-susceptible one by scavenging ROS in the hypoxic core of the solid tumor. After intravenous injection, the MTS@HMO nano-assembly was able to sense and be degraded by the abundant ROS in the hypoxic TME, thereby releasing HMO particles for subsequent scavenging of H2O2. The oxygen generated during peroxide scavenging then relieved the hypoxic TME, thereby resulting in an increased sensitivity of the hypoxic tumor tissue towards RT. Moreover, the in situ hypoxic status was monitored via the T1-enhanced magnetic resonance (MR) imaging of the Mn2+ ions generated by the ROS-mediated degradation of HMO. The in vitro results demonstrated a significant H2O2 elimination and enhanced oxygen generation after the treatment of the MTS@HMO nano-assembly with tumor cells under hypoxic conditions, compared to the control MTS group. In addition, the combination of RT and pre-treatment with MTS@HMO nano-assembly significantly amplified the permanent DNA strand breaks in tumor cells compared to the control RT group. More importantly, the in vivo results proved that the systemic injection of the MTS@HMO nano-assembly prior to RT irradiation enhanced the RT-mediated tumor suppression and down-regulated the hypoxic marker of HIF-1α in the solid tumor compared to the control RT group. Overall, the present work demonstrates the great potential of the versatile ROS-catalytic hypoxia modulating strategy using the MTS@HMO nano-assembly to enhance the RT-induced antitumor efficacy in hypoxic solid tumors.
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Neoplasias del Colon , Fotoquimioterapia , Humanos , Especies Reactivas de Oxígeno/metabolismo , Peróxido de Hidrógeno/química , Línea Celular Tumoral , Hipoxia/tratamiento farmacológico , Hipoxia/metabolismo , Hipoxia/patología , Oxígeno/metabolismo , Neoplasias del Colon/radioterapia , Neoplasias del Colon/tratamiento farmacológico , Microambiente Tumoral , Fotoquimioterapia/métodosRESUMEN
PURPOSE: To prospectively evaluate the potential of four-dimensional (4D) flow magnetic resonance imaging (MRI) in predicting treatment responses after transcatheter arterial chemoembolization (TACE) in cirrhotic patients with hepatocellular carcinoma (HCC). METHODS: A total of 195 patients were classified into four groups (A-D): A, cirrhotic patients without HCC (n = 30); B, cirrhotic patients with HCC before TACE (n = 75); C, cirrhotic patients with HCC showing an incomplete response following TACE (n = 56); and D, cirrhotic patients with HCC achieving a complete response (CR) following TACE (n = 34). The patients were subjected to routine laboratory tests and 4D flow MRI using a 3-T MRI system to measure the quantitative parameters of blood flow in the portal vein (PV), splenic vein (SV), and superior mesenteric vein. The data collected by 4D flow MRI were compared among the groups using one-way analysis of variance. A multivariate analysis was performed to verify the association of clinical characteristics and 4D flow parameters with CR after TACE treatment. RESULTS: The average through-plane velocity, peak velocity magnitude, average net flow, peak flow, and net forward volume in the PV and SV were significantly lower in groups B and C (P < 0.05) compared to those in group A. Moreover, average through-plane velocity and peak velocity magnitude in the PV in groups B and C were significantly lower than those in group D (P < 0.05). The multivariate analysis demonstrated that the average through-plane velocity and peak velocity magnitude in the PV were independently associated with CR in HCC patients after TACE (P < 0.05). CONCLUSION: The quantitative flow data obtained by 4D flow MRI may be useful for predicting CR after TACE in cirrhotic patients with HCC.
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Cell therapy is targeted at many organs, but locally or systemically delivered cells are shortly able to survive resulting from the immune/inflammation reactions and irregular cell targeting. Here we explore the multimodal nanoparticle having anti-inflammation and magnetic guidance for successful cell transplantation. We design magnetic resonance (MR)-active glycyrrhizin-chitosan coated superparamagnetic iron oxide nanoparticle (SPIO@Chitosan-GL) to inhibit release of inflammatory damage-associated molecular pattern (DAMP) protein and to offer noninvasive monitoring after intrahepatic transplantation of pancreatic islets and mesenchymal stem cell (MSC) spheroids. Intracellular delivered SPIO@Chitosan-GL is not cytotoxic to pancreatic islets and MSC spheroids and attenuate DAMP release from them. Also, therapeutic cells labeled with SPIO@Chitosan-GL are magnetically localized to the intended lobe of liver during transplantation procedure. If necessary, partial hepatectomy can be performed to remove the localized therapeutic cells for protection of the remaining liver lobes from systemic inflammation. Therapeutically, the cells selectively localized in the liver can treat blood glucose in diabetic mice to normal levels with DAMP modulation, and are visualized using in vivo MR imaging for over 4 weeks. Collectively, DAMP-modulating SPIO@Chitosan-GL can be used in multimodal nanomedince for attenuating the inflammation reaction by transplanted cells and for noninvasively long-term monitoring of transplanted cells.
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Herein, nanogap amplified plasmonic heat-generators are fabricated by decorating Pt nanodots on gold nanospheres (GNSs@Pt@mPEG) by maintaining strategic nano-gaps (1-2 nm) and studied precisely for plasmonic photothermal therapy (PPTT) of colon cancer by passive tumor targeting. The surface modification of GNSs@Pt with poly(ethylene glycol) methyl ether thiol (mPEG) increases their accumulation in tumor cells and hence the GNSs@Pt@mPEG stay at the tumor site for a longer time. The nanogap amplified GNSs@Pt@mPEG (O.D. = 4.0) generated high plasmonic photothermal hyperthermia and utilized a low NIR power density (0.36 W cm-2) for the elimination of tumor cells in only 150 s of irradiation time and shows excellent colloidal and photo-stability. The predominant distribution of GNSs@Pt@mPEG caused effective tumor cell death and promoted uniform treatment on tumor sites. In vivo studies demonstrated that the GNSs@Pt@mPEG have very low toxicity, high biocompatibility, and thermal stability, stay longer at the tumor site, induce tumor cell death without side effects, and show significantly less uptake in other organs except for the spleen. The significant accumulations and longer stay suggested that they are favorable for tumor passive uptake and the possibility of enhanced PPTT after intravenous administration. The nano-particles were stable up to O.D. 200 and have at least 12 months shelf-life without losing colloidal stability or photothermal efficacy. These findings lay the groundwork for using GNSs@Pt@mPEG as a NIR light-responsive PPTT agent and demonstrated their potential for further use in clinical applications.
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Hipertermia Inducida , Neoplasias , Línea Celular Tumoral , Oro/farmacología , Humanos , Rayos Láser , Neoplasias/tratamiento farmacológico , FototerapiaRESUMEN
RATIONALE AND OBJECTIVES: Magnetic resonance imaging (MRI) is the most useful imaging tool for small hepatocellular carcinoma (HCC) evaluation. Patients undergoing transarterial chemoembolization (TACE) might have predictive imaging prognostic factors. This study aimed to find predictive gadoxetic acid (GA)-enhanced MRI features that affect tumor response and outcomes in patients with early HCC who underwent conventional TACE. MATERIALS AND METHODS: Among patients who underwent conventional TACE as a first-line treatment for Barcelona clinic liver cancer stage 0 or A (<3 cm), 135 patients who underwent GA-enhanced MRI before treatment were included in this retrospective study. The patients' pretreatment clinical characteristics and MRI features were evaluated. Post-treatment tumor response, progression-free survival (PFS), and overall survival (OS) were also investigated. RESULTS: The median follow-up period was 47 (range: 7-133) months, with 90 (67%) patients showing complete remission (CR) at the 1-month follow-up after TACE. Tumor number (odds ratio [OR] 0.602, 95% confidence interval [CI]: 0.375-0.967), central location (OR: 0.349, 95% CI: 0.145-0.837) were inversely associated with CR achievement. Median PFS and OS time were 22 (range: 1-133) and 67 (range: 7-133) months, respectively. The MRI features affecting poor survival outcomes were tumor number (PFS: hazard ratio [HR]=1.444, 95% CI=1.124-1.854; OS: HR=1.459, 95% CI=1.018-2.090), central location (PFS: HR=1.664, 95% CI=1.038-2.667; OS: HR=1.890, 95% CI=1.021-3.497), and marginal irregularity (PFS: HR=3.099, 95% CI=1.953-4.979; OS: HR=1.985, 95% CI=1.084-3.634). CONCLUSION: Multiplicity, central location, and marginal irregularity of HCC on GA-enhanced MRI were significant factors associated with poor prognosis of patients with early HCC after conventional TACE.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Gadolinio DTPA , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/terapia , Imagen por Resonancia Magnética , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Although off-midline incisions (unilateral low transverse or Pfannenstiel incision) have been reported to have a lower incidence of incisional hernia (IH) than periumbilical vertical incision for the purpose of specimen extraction, it is most commonly used in laparoscopic colon cancer surgery because off-midline incisions are associated with the limitation of colon exteriorization. This study aims to investigate the risk of IH after laparoscopic colectomy and compare midline vertical incision versus transverse incision focusing on the incidence of IH. METHODS: Patients who underwent elective laparoscopic colectomy due to colon malignancy from June 2015 to May 2017 were included. All patients had either vertical (n = 429) or muscle splitting periumbilical transverse incisions (n = 125). RESULTS: Median duration of the follow-up period was 23.6 months, during which IHs occurred in 12.1% patients. The incidence of hernia was significantly lower in the transverse group (3 vs. 64, 2.4% vs. 14.9%, p < 0.001). On multivariate analysis, BMI ≥ 23 [odds ratio (OR) 2.282, 95% confidence interval (CI) 1.245-4.182, p = 0.008], postoperative surgical site infection (OR 3.780, 95% CI 1.969-7.254, p < 0.001) and vertical incision (OR 7.113, 95% CI 2.173-23.287, p < 0.001) were independently related with increased incidence of IH. CONCLUSIONS: A muscle splitting periumbilical transverse incision could significantly reduce the rate of IH in minimally invasive colon cancer surgery.
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Neoplasias del Colon , Hernia Incisional , Laparoscopía , Colectomía/efectos adversos , Neoplasias del Colon/complicaciones , Neoplasias del Colon/cirugía , Humanos , Hernia Incisional/epidemiología , Hernia Incisional/etiología , Hernia Incisional/prevención & control , Laparoscopía/efectos adversos , Factores de RiesgoRESUMEN
To identify the gadoxetic acid (GA)-enhanced magnetic resonance imaging (MRI) and laboratory findings that enable prediction of treatment response and disease-free survival (DFS) after the first session of drug eluting bead transarterial chemoembolization (DEB-TACE) in patients with hepatocellular carcinoma (HCC). A total of 55 patients who underwent GA-enhanced MRI and DEB-TACE from January 2014 to December 2018 were included. All MRI features were reviewed by two radiologists. Treatment response was evaluated according to the modified Response Evaluation Criteria in Solid Tumors. Univariate and multivariate logistic regression analyses were used to determine predictive factors of treatment response and DFS, respectively. A total of 27 patients (49.1%) achieved complete response (CR) after one session of treatment. There were no significant differences between the two groups in terms of clinical and laboratory characteristics. Heterogeneous signal intensity in the hepatobiliary phase (HBP) was the only independent predictor of non-CR (odds ratio, 4.807; p = 0.048). Recurrent HCC was detected in 19 patients (70.4%) after CR. In the multivariate analysis, elevated serum alpha-fetoprotein (AFP) level (≥ 30 ng/mL) was the only significant parameter associated with DFS (hazard ratio, 2.916; p = 0.040). This preliminary study demonstrated that heterogeneous signal intensity in the HBP and high serum AFP were useful predictive factors for poor treatment response and short DFS after DEB-TACE, respectively.
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Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Imagen por Resonancia Magnética , Anciano , Biomarcadores de Tumor , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/mortalidad , Quimioembolización Terapéutica/efectos adversos , Comorbilidad , Manejo de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/mortalidad , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Oportunidad Relativa , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento , Carga TumoralRESUMEN
Immunotherapy has been investigated for decades, and it has provided promising results in preclinical studies. The most important issue that hinders researchers from advancing to clinical studies is the delivery system for immunotherapy agents, such as antigens, adjuvants and agonists, and the activation of these agents at the tumour site. Polymers are among the most versatile materials for a variety of treatments and diagnostics, and some polymers are reactive to either endogenous or exogenous stimuli. Utilizing this advantage, researchers have been developing novel and effective polymeric nanomaterials that can deliver immunotherapeutic moieties. In this review, we summarized recent works on stimuli-responsive polymeric nanomaterials that deliver antigens, adjuvants and agonists to tumours for immunotherapy purposes.
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Adyuvantes Inmunológicos/uso terapéutico , Antígenos/uso terapéutico , Inmunoterapia , Neoplasias/terapia , Antígenos/inmunología , Humanos , Nanoestructuras/uso terapéutico , Neoplasias/inmunología , Polímeros/uso terapéuticoRESUMEN
BACKGROUND: The objective of this study was to evaluate the effect of music with noise-canceling headphones on men undergoing transrectal ultrasound-guided prostate biopsy (TRUSPB) in a prospective randomized study. METHODS: From January to February 2020, 94 men underwent TRUSPB at our institution. They were divided into two groups and wore noise-cancelling headphones-group 1 (n = 47) did not listen to music and group 2 (n = 47) listened to music. We examined the patients' clinical characteristics and compared the objective and subjective measurements before and after the procedures. Primary outcomes included vital signs, the State-Trait Anxiety Inventory (STAI, 20-80) scale; and the visual analog scale (VAS, 0-10) for the assessments of pain, satisfaction, and willingness to repeat the procedure. RESULTS: There were no significant differences in patients' characteristics or the prebiopsy status between the groups. Postbiopsy vital signs for objective parameters were statistically similar between the groups; however, the subjective parameters were not. Postbiopsy STAI-state and VAS scores were significantly lower and VAS scores for the patients' satisfaction and willingness to repeat the procedure were significantly higher in Group 2 than in Group 1 (p = 0.004, p = 0.009, p = 0.004, and p = 0.003, respectively). In addition, changes in the STAI-state score before and after the procedure were significant in Group 2 (p = 0.001). CONCLUSIONS: Music from noise-canceling headphones may have beneficial effects on anxiety, pain, satisfaction, and willingness to repeat the procedure in men undergoing TRUSPB.
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INTRODUCTION: Paclitaxel (PTX) is a conventional chemotherapeutic drug that effectively treats various cancers. The cellular uptake and therapeutic potential of PTX are limited by its slow penetration and low solubility in water. The development of cancer chemotherapy methods is currently facing considerable challenges with respect to the delivery of the drugs, particularly in targeting the tumor site without exerting detrimental effects on the healthy surrounding cells. One possibility for improving the therapeutic potential is through the development of tumor-targeted delivery methods. METHODS: We successfully synthesized paclitaxel-MHI-148 conjugates (PTX-MHI) by coupling PTX with the tumor-targeting heptamethine cyanine dye MHI-148. Synthesis and purification were characterized using the absorbance spectrum and the results of time-of-flight mass spectrometry. Cellular uptake and cytotoxicity studies were conducted in vitro and in vivo. RESULTS: PTX-MHI accumulates in tumor cells but not in normal cells, as observed by in vitro near-infrared fluorescent (NIRF) imaging along with in vivo NIRF imaging and organ biodistribution studies. We observed that MHI-148-conjugated PTX shows greater efficiency in cancer cells than PTX alone, even in the absence of light treatment. PTX-MHI could also be used for specific drug delivery to intracellular compartments, such as the mitochondria and lysosomes of cancer cells, to improve the outcomes of tumor-targeting therapy. CONCLUSION: The results indicated that PTX-MHI-mediated cancer therapy exerts an excellent inhibitory effect on colon carcinoma (HT-29) cell growth with low toxicity in normal fibroblasts (NIH3T3).
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Nanopartículas , Paclitaxel , Animales , Carbocianinas , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Indoles , Ratones , Ratones Desnudos , Células 3T3 NIH , Distribución TisularRESUMEN
The goal of this study was to determine the diagnostic performance of in vivo quantitative proton magnetic resonance spectroscopy (1H-MRS) to identify the presence of esophageal varices needing treatment (VNT), as well as investigate its correlation with clinical characteristics in patients with liver cirrhosis. Forty cirrhotic patients without VNT showing the negative red color sign, and 40 cirrhotic patients with VNT showing positive red color sign underwent laboratory tests, esophago-gastro-duodenoscopy, and 1H-MRS with single-voxel localization in the cirrhotic liver parenchyma. The levels of lactate + triglyceride (TG) and choline in cirrhotic patients with VNT were significantly higher than those in cirrhotic patients without VNT. In multivariate analysis, spleen diameter, platelet count, and platelet count/spleen diameter ratio, as well as lactate + TG, and choline were associated with the presence of VNT. Moreover, lactate + TG and choline levels were positively correlated with spleen diameter and negatively correlated with platelet count in the combined group of cirrhotic patients with and without VNT. Our study demonstrated that higher hepatic lactate + TG and choline levels in cirrhotic patients in conjunction with longer spleen diameter, lower platelet counts, and lower ratios of platelet count to spleen diameter were associated with the presence of esophageal VNT and the risk of developing variceal bleeding. Therefore, in vivo 1H-MRS might be an effective tool for diagnosing and predicting esophageal VNT in patients with liver cirrhosis.
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Biomarcadores , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/metabolismo , Cirrosis Hepática/complicaciones , Toma de Decisiones Clínicas , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Diagnóstico por Imagen de Elasticidad , Endoscopía del Sistema Digestivo , Várices Esofágicas y Gástricas/diagnóstico , Várices Esofágicas y Gástricas/terapia , Humanos , Cirrosis Hepática/diagnóstico , Pruebas de Función Hepática , Imagen por Resonancia Magnética , Pruebas de Función Plaquetaria , Pronóstico , Bazo/patologíaRESUMEN
[This corrects the article DOI: 10.3389/fmolb.2020.610533.].
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Purpose: To compare the per-patient diagnostic performance of simulated abbreviated MRI (AMRI) to that of conventional MRI (CMRI) with full-sequence dynamic gadoxetic acid (GA) enhancement for early-stage hepatocellular carcinoma (HCC) screening in high-risk patients. Materials and Methods: A total of 201 consecutive patients at high-risk for HCC, who underwent 3T liver MRI, were included in this retrospective study. The AMRI protocol comprised T2-weighted imaging, hepatobiliary phase imaging after GA injection, and diffusion-weighted imaging. For each patient, two AMRI and CMRI image sets were independently reviewed by two radiologists. Inter-reader agreement was assessed using Cohen's kappa value. A composite reference standard was used to determine the diagnostic performance of each image set for each reader. Results: A total of 93 HCCs were detected in 79 patients. The inter-reader agreement was almost perfect for both image sets (κ = 0.839, 0.948). In AMRI, the per-patient sensitivity and negative predictive values (NPV) were 94.9% and 96.4%, respectively. In CMRI, the per-patient sensitivity and NPV were 96.2% and 97.5%, respectively. Conclusion: AMRI, using only three sequences, had a comparable diagnostic performance to CMRI in screening early-stage HCC. AMRI could be an alternative HCC screening tool for high-risk HCC patients.
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The uterus can be largely divided into the uterine corpus and uterine cervix. Diseases that can occur in the uterine corpus, composed of the endometrium and myometrium, vary from benign to malignant tumors. Ultrasound and CT are the primary non-invasive evaluation methods to differentiate between benign and malignant tumors, but in some cases, they are difficult to differentiate due to their non-specific imaging findings. However, magnetic resonance imaging (MRI), which has high resolution, helps not only in locating lesions but also in evaluating histological characteristics and staging of malignant tumors. In this review article, the characteristic MRI findings that radiologists should be aware of regarding various benign and malignant tumors detected in the uterine corpus are summarized with their points of differentiation.
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Magnetic resonance imaging (MRI) has become a crucial tool for evaluating mediastinal masses considering that several lesions that appear indeterminate on computed tomography and radiography can be differentiated on MRI. Using a three-compartment model to localize the mass and employing a basic knowledge of MRI, radiologists can easily diagnose mediastinal masses. Here, we review the use of MRI in evaluating mediastinal masses and present the images of various mediastinal masses categorized using the International Thymic Malignancy Interest Group's three-compartment classification system. These masses include thymic hyperplasia, thymic cyst, pericardial cyst, thymoma, mediastinal hemangioma, lymphoma, mature teratoma, bronchogenic cyst, esophageal duplication cyst, mediastinal thyroid carcinoma originating from ectopic thyroid tissue, mediastinal liposarcoma, mediastinal pancreatic pseudocyst, neurogenic tumor, meningocele, and plasmacytoma.