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1.
Odontology ; 111(1): 172-177, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35554774

RESUMEN

Understanding the variations in root canal morphology is important for successful endodontic treatment. Mandibular first premolars have a single root in 98% of cases, and multiple root canals are found in approximately 20% of cases. However, the details of these characteristic findings in panoramic radiography and their diagnostic accuracy are unknown. This study aimed to investigate the characteristic radiographic findings of mandibular first premolars possessing multiple root canals and determine the diagnostic accuracy using panoramic radiography. Four radiologists evaluated 347 mandibular first premolars in 186 patients who underwent panoramic radiography and dental cone beam computed tomography (CBCT). Two radiologists confirmed the existence of single or multiple root canals using CBCT. The remaining two radiologists evaluated the imaging findings of the root canal morphology and classified them into two patterns: gradual narrowing and sudden narrowing. In the case of the sudden narrowing pattern, the location of sudden narrowing was also evaluated. A gradual narrowing pattern was observed in 56% of teeth with a single root canal, and a sudden narrowing pattern was observed in 83% of teeth with multiple root canals. When sudden narrowing between the cervical and apical 1/4 of the root canal was used as the diagnostic criterion for multiple root canal teeth, the highest diagnostic performance was observed (sensitivity, 76.1%; specificity, 73.9%). The sudden narrowing between the cervical level and the apical 1/4 level of the root canal is a practical diagnostic criterion for mandibular first premolar with multiple root canals.


Asunto(s)
Cavidad Pulpar , Mandíbula , Humanos , Radiografía Panorámica , Cavidad Pulpar/diagnóstico por imagen , Diente Premolar/diagnóstico por imagen , Diente Premolar/anatomía & histología , Mandíbula/diagnóstico por imagen , Tomografía Computarizada de Haz Cónico/métodos , Raíz del Diente
2.
Cancer Sci ; 114(1): 227-235, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36056924

RESUMEN

Chemotherapy using a lymphatic drug delivery system (LDDS) targeting lymph nodes (LNs) in the early stage of metastasis has a superior antitumor effect to systemic chemotherapy. An LDDS produces a higher drug retention rate and tissue selectivity in LNs. To expand the therapeutic coverage of LDDS from local treatment of metastatic LNs to prevention of distant metastases, the combination of treatment with therapies that enhance systemic tumor immune effects is an important therapeutic strategy. Recently, total body irradiation (TBI) has been shown to activate immune responses and alter the tumor microenvironment. Here we show that combination therapy with TBI and LDDS improves the antitumor effect of metastatic LNs and lung metastasis. Tumor cells were inoculated into the subiliac LN (SiLN) to induce metastasis into the proper axillary LN (PALN) and lung in a mouse model. TBI was carried out on day 4 after inoculation using a gamma irradiator. Lymphatic drug delivery into the accessory axillary LN was used to treat PALN. In vivo bioluminescence imaging, high-frequency ultrasound, and histology showed that combination therapy using TBI (total dose 1.0 Gy once) and the LDDS suppressed tumor growth in LNs and lung metastases and was more effective than using LDDS or TBI alone. Quantitative RT-PCR of spleens after combination therapy revealed increased expression of CD4, CD8, and IL-12b, indicating an activated immune response. The results show that combination therapy with TBI and LDDS is a method to improve the efficacy of LN metastases and distant metastases therapy and is a promising novel approach to treat cancer patients.


Asunto(s)
Neoplasias Pulmonares , Irradiación Corporal Total , Ratones , Animales , Ganglios Linfáticos/patología , Sistemas de Liberación de Medicamentos , Pulmón , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Microambiente Tumoral
3.
Clin Exp Metastasis ; 39(3): 421-431, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35119560

RESUMEN

A perfusion defect (PD) in non-enlarged lymph nodes (LNs) of oral squamous cell carcinoma (OSCC) is the most reliable radiological criterion for the diagnosis of metastasis. However, conventional contrast-enhanced (CE) T1 weighted images using turbo spin echo (TSE) sequence is limited in detecting PD in non-enlarged LNs due to flow artifacts from cervical blood vessels. Vessel wall (VW) MR imaging with blood vessel flow suppression and high spatial resolution may provide new insights into the detection of PD. However, there are no reports in the literature on the usefulness of VW MR imaging for the diagnosis of LN metastasis. It is demonstrated that PD of non-enlarged LNs in CE VR MR imaging of OSCC patients is useful for the diagnosis of metastatic LNs. VW MR imaging was significantly more sensitive in detecting PD of non-enlarged metastatic LNs than conventional TSE imaging on visual evaluation. Furthermore, it was found that the image contrast between PD and surrounding intranodal tissue in CE VW MR images was higher than that in conventional CE TSE images. In the correlation between imaging and histopathological findings of metastatic LNs, all LNs that exhibited PD on CE VW MR images were at an advanced histopathological metastatic stage. The pathology of PD was necrotic tissue with keratinization. The results indicated that PD in CE VW imaging is useful in diagnosing non-enlarged LNs at an advanced metastasis stage. The addition of VW MR imaging to conventional MR examination achieves higher diagnostic performance for non-enlarged metastatic LNs.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Neoplasias de Cabeza y Cuello/patología , Humanos , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética , Neoplasias de la Boca/diagnóstico por imagen , Neoplasias de la Boca/patología , Perfusión , Carcinoma de Células Escamosas de Cabeza y Cuello/patología
4.
Oral Radiol ; 38(2): 224-233, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34245408

RESUMEN

OBJECTIVES: The most typical maxillofacial feature of patients with acromegaly is mandibular protrusion. This study aimed to determine differences in maxillofacial morphology between skeletal Class III patients with and without acromegaly using cephalometric analysis. METHODS: Cephalograms of 37 patients with acromegaly (Acro), 37 age-matched non-acromegalic patients with skeletal Class III malocclusion (C-III), and 37 age-matched Class I malocclusion patients (C-I; control) were retrospectively collected. The skeletal and dental morphology of each group was analyzed using cephalometric analysis, which included linear and angular measurements and facial profilograms. In addition, we analyzed diagnostic performance and cutoff values for discriminating acromegaly from skeletal Class III malocclusion using receiver operating characteristic (ROC) curve analysis. RESULTS: The mandibular ramus height was larger in the Acro group than in the other groups. The increase in L1/MP in the Acro group, which represented labial inclination of the mandibular central incisors, was the most characteristic feature in this study. ROC curve analysis indicated that a cutoff value of 88.4° for L1/MP had the highest diagnostic performance in discriminating acromegaly from non-acromegalic Class III malocclusion. CONCLUSIONS: Acromegaly was characterized by a greater degree of bimaxillary prognathism than was non-acromegalic Class III malocclusion. Focusing on labial inclination of the mandibular central incisors would be the most useful way to differentiate acromegaly from non-acromegalic Class III malocclusion.


Asunto(s)
Acromegalia , Maloclusión de Angle Clase III , Acromegalia/diagnóstico por imagen , Cefalometría , Humanos , Maloclusión de Angle Clase III/diagnóstico por imagen , Proyectos Piloto , Estudios Retrospectivos
5.
Clin Exp Metastasis ; 38(6): 539-549, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34654990

RESUMEN

A perfusion defect in a metastatic lymph node (LN) can be visualized as a localized area of low contrast on contrast-enhanced CT, MRI or ultrasound images. Hypotheses for perfusion defects include abnormal hemodynamics in neovascular vessels or a decrease in blood flow in pre-existing blood vessels in the parenchyma due to compression by LN tumor growth. However, the mechanisms underlying perfusion defects in LNs during the early stage of LN metastasis have not been investigated. We show that tumor mass formation with very few microvessels was associated with a perfusion defect in a non-enlarged LN at the early stage of LN metastasis in a LN adenopathy mouse (LN size circa 10 mm). We found in a mouse model of LN metastasis, induced using non-keratinizing tumor cells, that during the formation of the perfusion defect in a non-enlarged LN, the number of blood vessels ≤ 50 µm in diameter decreased, while those of > 50 µm in diameter increased. The methods used were contrast-enhanced high-frequency ultrasound and contrast-enhanced micro-CT imaging systems, with a maximum spatial resolution of > 30 µm. Furthermore, we found no tumor angiogenesis or oxygen partial pressure (pO2) changes in the metastatic LN. Our results demonstrate that the perfusion defect appears to be a specific form of tumorigenesis in the LN, which is a vascular-rich organ. We anticipate that a perfusion defect on ultrasound, CT or MRI images will be used as an indicator of a non-enlarged metastatic LN at an early stage.


Asunto(s)
Histiocitoma Fibroso Maligno/patología , Ganglios Linfáticos/irrigación sanguínea , Neoplasias Mamarias Experimentales/patología , Imagen de Perfusión , Ultrasonografía , Microtomografía por Rayos X , Animales , Línea Celular Tumoral , Femenino , Metástasis Linfática , Ratones , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Flujo Sanguíneo Regional , Factores de Tiempo
6.
Oral Oncol ; 120: 105453, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34265573

RESUMEN

OBJECTIVES: To evaluate the ability of different imaging modalities to accurately detect bone invasion in oral squamous cell carcinomas. PATIENTS AND METHODS: Patients with oral squamous cell carcinoma, who were scheduled for mandibulectomy or maxillectomy, underwent clinical evaluation using five preoperative imaging diagnosis methods-contrast-enhanced MRI, CT, 99mTc scintigraphy (Tc scan), FDG-PET CT (PET/CT), and panoramic radiography. The sensitivity and specificity of each modality in detecting bone invasion were calculated by comparing the findings on the images with postoperative histopathological findings. In a subgroup of patients, we further assessed the ability of MRI and CT to detect the accurate extent of bone invasion, including the height, width, and depth in patients with pathological mandibular invasion. RESULTS: Overall, 50 patients were enrolled in this study, and nine patients with pathological mandibular invasion were included in our subgroup analysis. MRI was found to be the most useful method in detecting bone invasion, showing the highest sensitivity (88.9%) and negative predictive values (92.3%). CT (87.5% specificity and 77.8% sensitivity) was more specific than MRI, though less sensitive. Combined PET/CT was more sensitive (83.3%) and less specific (71.9%) than CT. Tc scan had high sensitivity (88.9%); however, the specificity was relatively low (71.9%). CONCLUSION: MRI was the most useful method in detecting bone invasion. A negative MRI result definitively excludes bone marrow invasion. In patients with positive MRI findings, a negative CT may be useful in ruling out bone marrow invasion.


Asunto(s)
Mandíbula/patología , Neoplasias de la Boca , Invasividad Neoplásica/diagnóstico por imagen , Carcinoma de Células Escamosas de Cabeza y Cuello , Fluorodesoxiglucosa F18 , Humanos , Imagen por Resonancia Magnética , Neoplasias de la Boca/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Sensibilidad y Especificidad , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico por imagen , Tomografía Computarizada por Rayos X
7.
Cancer Sci ; 112(5): 1735-1745, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33629407

RESUMEN

Lymph node (LN) metastasis is thought to account for 20-30% of deaths from head and neck cancer. The lymphatic drug delivery system (LDDS) is a new technology that enables the injection of drugs into a sentinel LN (SLN) during the early stage of tumor metastasis to treat the SLN and secondary metastatic LNs. However, the optimal physicochemical properties of the solvent used to carry the drug have not been determined. Here, we show that the osmotic pressure and viscosity of the solvent influenced the antitumor effect of cisplatin (CDDP) in a mouse model of LN metastasis. Tumor cells were inoculated into the proper axillary LN (PALN), and the LDDS was used to inject CDDP solution into the subiliac LN (SiLN) to treat the tumor cells in the downstream PALN. CDDP dissolved in saline had no therapeutic effects in the PALN after it was injected into the SiLN using the LDDS or into the tail vein (as a control). However, CDDP solution with an osmotic pressure of ~ 1,900 kPa and a viscosity of ~ 12 mPa⋅s suppressed tumor growth in the PALN after it was injected into the SiLN using the LDDS. The high osmotic pressure dilated the lymphatic vessels and sinuses to enhance drug flow in the PALN, and the high viscosity increased the retention of CDDP in the PALN. Our results demonstrate that optimizing the osmotic pressure and viscosity of the solvent can enhance the effects of CDDP, and possibly other anticancer drugs, after administration using the LDDS.


Asunto(s)
Cisplatino/química , Metástasis Linfática/tratamiento farmacológico , Presión Osmótica , Ganglio Linfático Centinela , Solventes/química , Viscosidad , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Antineoplásicos/farmacocinética , Axila , Fenómenos Químicos , Cisplatino/administración & dosificación , Cisplatino/farmacocinética , Medios de Contraste , Modelos Animales de Enfermedad , Sistemas de Liberación de Medicamentos/métodos , Inyecciones Intralinfáticas/métodos , Luciferasas/metabolismo , Vasos Linfáticos/fisiología , Ratones , Solución Salina/administración & dosificación , Solución Salina/química , Ganglio Linfático Centinela/diagnóstico por imagen , Solventes/administración & dosificación , Solventes/farmacocinética , Ultrasonografía
8.
Case Rep Dent ; 2020: 8854428, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33029434

RESUMEN

A simple bone cyst (SBC) is an intrabone cavity without epithelial lining, which occasionally occur with fibrous-osseous lesions. The imaging finding of the scalloped border and conserving the lamina dura, periodontal ligament spaces, or follicular spaces are considered radiographically pathognomonic of SBC. SBC has been reported to occur with fibrous-osseous lesions, including cemento-osseous dysplasia (COD). Computed tomography (CT) imaging findings are sparse, and there are no reports of magnetic resonance imaging (MRI) findings, including apparent diffusion coefficient (ADC) value calculated by diffusion-weighted MRI for the florid COD-associated SBC. We report a case of a 39-year-old woman who was referred to our hospital because a panoramic radiograph of her right mandible showed asymptomatic radiolucency in the apical molar area. CT images showed a low-density lesion in the periapical areas of the right mandible, which accompanied a well-defined, high-density lesion, and a mixed low/high-density lesion with an unusual marked irregular border in the left mandible. The MRI showed cyst-like extremely hyperintense signals on fat-suppressed T2-weighted images at the right mandibular low-density and the left mandibular mixed low/high-density areas. ADC map showed high values (over 2.5 × 10-3 mm2/s) at the cystic areas in the bilateral mandible. We performed incisional biopsies of the bilateral mandibular lesions and resections of the bilateral maxillary lesions. Surgical and histopathological findings established a diagnosis of florid COD in the bilateral mandible and maxilla, simultaneously complicated by multiple SBCs in the bilateral mandible. The ADC value of cystic component is useful for the diagnosis, if the COD-associated SBC exhibits solitary, nonspecific, or rare imaging findings.

9.
Cancer Sci ; 111(11): 4232-4241, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32882076

RESUMEN

Cancer metastasis to lymph nodes (LNs) almost certainly contributes to distant metastasis. Elevation of LN internal pressure (intranodal pressure, INP) during tumor proliferation is associated with a poor prognosis for patients. We have previously reported that a lymphatic drug delivery system (LDDS) allows the direct delivery of anticancer drugs into the lymphatic system and is a promising treatment strategy for early-stage LN metastasis. However, methods for evaluating the treatment effects have not been established. Here, we used a mouse model of MXH10/Mo-lpr/lpr, which develops a systemic swelling of LNs, and murine malignant fibrous histiocytoma-like (KM-Luc/GFP) cells or murine breast cancer (FM3A-Luc) cells inoculated into the subiliac LN of mice to produce a tumor-bearing LN model. The changes in INP during intranodal tumor progression and after treatment with cis-dichlorodiammineplatinum(II) (CDDP) using an LDDS were measured. We found that tumor progression was associated with an increase in INP that occurred independently of LN volume changes. The elevation in INP was suppressed by CDDP treatment with the LDDS when intranodal tumor progression was significantly inhibited. These findings indicate that INP is a useful parameter for monitoring the therapeutic effect in patients with LN metastasis who have been given drugs using an LDDS, which will serve to manage cancer metastasis treatment and contribute to an improved quality of life for cancer patients.


Asunto(s)
Antineoplásicos/administración & dosificación , Sistemas de Liberación de Medicamentos , Ganglios Linfáticos/patología , Animales , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Femenino , Humanos , Inmunohistoquímica , Metástasis Linfática , Ratones , Neovascularización Patológica/diagnóstico por imagen , Neovascularización Patológica/patología , Ultrasonografía/métodos , Ensayos Antitumor por Modelo de Xenoinjerto
10.
Head Neck ; 42(10): 2896-2904, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32608548

RESUMEN

BACKGROUND: The usefulness of apparent diffusion coefficient (ADC) and diffusion-weighted magnetic resonance imaging (DWI) in the detection of malignant tumors has been reported. The purpose of this study is to clarify the role of ADC and DWI for diagnosis of skull base tumors. METHODS: A total of 27 patients with head and neck tumors with skull base invasions undergoing skull base surgery were enrolled in this study. Pathological findings of dural invasion and bone invasion were compared with the diagnostic imaging. RESULTS: Advanced magnetic resonance imaging techniques revealed that ADC values in regions of pathological bone and dural invasions were significantly lower than in regions of no invasion. The area under the curve of ADC in bone invasions and dural invasions were 0.957 and 0.894, respectively. CONCLUSIONS: Our findings indicate that ADC and DWI are useful tools for the diagnosis of head and neck tumors with skull base invasion.


Asunto(s)
Neoplasias de Cabeza y Cuello , Neoplasias de la Base del Cráneo , Imagen de Difusión por Resonancia Magnética , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Imagen por Resonancia Magnética , Base del Cráneo/diagnóstico por imagen , Base del Cráneo/cirugía , Neoplasias de la Base del Cráneo/diagnóstico por imagen , Neoplasias de la Base del Cráneo/cirugía
11.
Ann Nucl Med ; 34(9): 643-652, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32564300

RESUMEN

OBJECTIVE: A positron emission tomography (PET) scanner using a silicon photomultiplier (SiPM PET) in place of a photomultiplier tube significantly improves the spatial and time resolution. It may also improve the evaluation of smaller lesions compared to conventional (non-SiPM) PET scanners. We compared the maximum standardized uptake value (SUVmax), detection sensitivity, and morphological correlation using magnetic resonance imaging (MRI) for primary tongue squamous cell carcinoma between the SiPM PET and non-SiPM PET scanner. METHODS: We retrospectively reviewed the F-18 fluorodeoxyglucose (FDG) PET/CT features of tongue squamous cell carcinomas in consecutive, newly diagnosed, and pathologically verified patients. Twenty-five of 46 patients were scanned using SiPM PET scanner and the remaining 21 patients were scanned with a non-SiPM PET scanner. We compared the SUVmax and visual evaluation of primary tumor detectability, and the correlation between the PET-based and MRI-based tumor size (long axis, thickness, and volume). Differences in SUVmax and detection sensitivity for the primary tumor were analyzed using Welch's t test and Fisher's exact test, respectively. Correlations among the PET-based, MRI-based tumor size, and SUVmax were assessed using Spearman's rank correlation coefficient. RESULTS: SUVmax of both T1/T2 and T3/T4 primary tumors were significantly higher for the SiPM PET (T1/T2 mean SUVmax: 6.6 ± 4.3, T3/T4 mean SUVmax: 18.2 ± 9.8) than that for the non-SiPM PET (T1/T2 mean SUVmax: 3.4 ± 1.4, T3/T4 mean SUVmax: 10.2 ± 4.9) (P < 0.05). While all cases of T3/T4 primary tumors were detected by both PET scanners, the detection sensitivity for T1/T2 primary tumors was significantly higher for the SiPM PET (80%) than that for the non-SiPM PET (36.4%) (P < 0.05). MRI-based tumor size correlated significantly with SiPM PET-based tumor long axis (ρ = 0.74) and volume (ρ = 0.91), but not with the non-SiPM PET-based tumor long axis and volume in T1/T2 primary lesions. Correlation between MRI-based tumor size and SUVmax was significant in both PET scanners; however, no significant difference was observed between the two scanners. CONCLUSIONS: The SiPM PET provides better detection sensitivity and a reliable morphological correlation for the T1/T2 primary tongue tumors than the non-SiPM PET due to its high performance.


Asunto(s)
Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones/instrumentación , Silicio , Neoplasias de la Lengua/diagnóstico por imagen , Neoplasias de la Lengua/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto Joven
12.
Oral Radiol ; 36(4): 344-348, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-31583602

RESUMEN

OBJECTIVES: To ascertain the effects of exposure parameters (tube current and tube voltage) and the gutta-percha cone (GPC) size on root fracture-like artifacts obtained with cone-beam computed tomography (CBCT). METHODS: Fracture-like artifacts appearing on CBCT images of nine extracted human mandibular premolars filled with GPCs of size #50 or #80 were analyzed using six exposure factors: two tube voltages (80 kV and 110 kV); and three tube currents (4 mA, 7 mA, and 10 mA). On axial images, the gray value (GV) was recorded at three points: the mesiobuccal portion (MBP) as the sound dentin, the mesial portion (MP) as the artifact line, and the water area (WA). The rate of decrease in the GV (RDGV) of the artifact line was calculated using the formula: RDGV (%) = (GV of MBP - GV of MP) × 100/(GV of MBP - GV of WA). RESULTS: Comparison of the #80 group and the #50 group with equal tube voltages and tube currents shows that artifact lines in the #80 group were more obvious than those in the #50 group. The artifact lines with 80 kV were markedly more visible than those with 110 kV for each tube current and GPC size. Tube current changes did not affect the artifact line for any tube voltage or GPC size. CONCLUSIONS: For the reduction of artifacts, we recommend selection of higher tube voltages and lower tube currents when taking CBCT images of teeth with each GPC size.


Asunto(s)
Materiales de Obturación del Conducto Radicular , Fracturas de los Dientes , Diente no Vital , Artefactos , Tomografía Computarizada de Haz Cónico , Gutapercha , Humanos
13.
Clin Transl Radiat Oncol ; 20: 53-57, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31886422

RESUMEN

Utilizing mice with swollen lymph nodes, we succeeded in irradiating individual metastatic lymph nodes through a hole in a lead shield. This system enabled us to increase the radiation dose to >8 Gy (the lethal dose for total-body irradiation) and evaluate both direct and abscopal antitumor effects.

14.
Sci Rep ; 9(1): 16029, 2019 11 05.
Artículo en Inglés | MEDLINE | ID: mdl-31690726

RESUMEN

Therapies targeting tumor vasculature would improve the treatment of lung metastasis, although the early changes in vascular structure are incompletely understood. Here, we show that obstructive metastatic foci in lung arterioles decrease the pulmonary vascular network. To generate a mouse model of lung metastasis activation, luciferase-expressing tumor cells were inoculated into the subiliac lymph node (SiLN) of an MXH10/Mo-lpr/lpr mouse, and metastatic tumor cells in the lungs were activated by SiLN resection. Activation of metastases was monitored by in vivo bioluminescence imaging. Pulmonary blood vessel characteristics were analyzed using ex vivo micro-computed tomography. The enhanced permeability and retention (EPR) effect in neovasculature after tumor cell activation was evaluated from the accumulation of intravenously injected indocyanine green (ICG) liposomes. Metastatic foci in lung arterioles were investigated histologically. Micro-computed tomography revealed decreases in pulmonary blood vessel length, volume and number of branching nodes during the early stage of metastasis caused by metastatic foci. ICG liposome accumulation by the EPR effect was not detected. Histology identified metastatic foci in lung arterioles. The lack of an EPR effect after the formation of metastatic foci in lung arterioles makes conventional systemic chemotherapy ineffective for lung metastasis. Thus, alternative therapeutic methods of drug delivery are needed.


Asunto(s)
Neoplasias Pulmonares/patología , Pulmón/irrigación sanguínea , Neovascularización Patológica , Animales , Vasos Sanguíneos/diagnóstico por imagen , Vasos Sanguíneos/fisiología , Modelos Animales de Enfermedad , Femenino , Verde de Indocianina/química , Liposomas/química , Pulmón/patología , Neoplasias Pulmonares/irrigación sanguínea , Ganglios Linfáticos/patología , Masculino , Ratones , Metástasis de la Neoplasia , Microtomografía por Rayos X
15.
Sci Rep ; 9(1): 13242, 2019 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-31519920

RESUMEN

Lymph node (LN) metastasis through the lymphatic network is a major route for cancer dissemination. Tumor cells reach the marginal sinuses of LNs via afferent lymphatic vessels (LVs) and form metastatic lesions that lead to distant metastasis. Thus, targeting of metastatic cells in the marginal sinuses could improve cancer treatment outcomes. Here, we investigated whether lymphatic administration of a drug combined with sonoporation could be used to treat a LN containing proliferating murine FM3A breast cancer cells, which are highly invasive, in its marginal sinus. First, we used contrast-enhanced high-frequency ultrasound and histopathology to analyze the structure of LVs in MXH10/Mo-lpr/lpr mice, which exhibit systemic lymphadenopathy. We found that contrast agent injected into the subiliac LN flowed into the marginal sinus of the proper axillary LN (PALN) and reached the cortex. Next, we examined the anti-tumor effects of our proposed technique. We found that a strong anti-tumor effect was achieved by lymphatic administration of doxorubicin and sonoporation. Furthermore, our proposed method prevented tumor cells in the marginal sinus from invading the parenchyma of the PALN and resulted in tumor necrosis. We conclude that lymphatic administration of a drug combined with sonoporation could exert a curative effect in LNs containing metastatic cells in their marginal sinuses.


Asunto(s)
Doxorrubicina/administración & dosificación , Sistemas de Liberación de Medicamentos , Ondas de Choque de Alta Energía , Ganglios Linfáticos/efectos de los fármacos , Neoplasias Mamarias Animales/tratamiento farmacológico , Sonicación/métodos , Animales , Antibióticos Antineoplásicos/administración & dosificación , Femenino , Ganglios Linfáticos/patología , Metástasis Linfática , Vasos Linfáticos/efectos de los fármacos , Vasos Linfáticos/patología , Neoplasias Mamarias Animales/patología , Ratones , Ratones Endogámicos C3H , Ratones Noqueados , Células Tumorales Cultivadas
16.
Cancer Med ; 8(5): 2241-2251, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30945479

RESUMEN

Metastatic lymph nodes (LNs) may be the origin of systemic metastases. It will be important to develop a strategy that prevents systemic metastasis by treating these LNs at an early stage. False-negative metastatic LNs, which are found during the early stage of metastasis development, are those that contain tumor cells but have a size and shape similar to LNs that do not host tumor cells. Here, we show that 5-fluorouracil (5-FU), delivered by means of a novel lymphatic drug delivery system (LDDS), can treat LNs with false-negative metastases in a mouse model. The effects of 5-FU on four cell lines were investigated using in vitro cytotoxicity and cell survival assays. The therapeutic effects of LDDS-administered 5-FU on false-negative metastatic LNs were evaluated using bioluminescence imaging, high-frequency ultrasound (US), and histology in MHX10/Mo-lpr/lpr mice. These experimental animals develop LNs that are similar in size to human LNs. We found that all cell lines showed sensitivity to 5-FU in the in vitro assays. Furthermore, a concentration-dependent effect of 5-FU to inhibit tumor growth was observed in tumor cells with low invasive growth characteristics, although a significant reduction in metastatic LN volume was not detected in MHX10/Mo-lpr/lpr mice. Adverse effects of 5-FU were not detected. 5-Fluorouracil administration with a LDDS is an effective treatment method for false-negative metastatic LNs. We anticipate that the delivery of anticancer drugs by a LDDS will be of great benefit in the prevention and treatment of cancer metastasis via LNs.


Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Fluorouracilo/administración & dosificación , Metástasis Linfática/tratamiento farmacológico , Animales , Antimetabolitos Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Reacciones Falso Negativas , Fluorouracilo/uso terapéutico , Humanos , Ratones , Resultado del Tratamiento , Ensayos Antitumor por Modelo de Xenoinjerto
17.
Mol Imaging Biol ; 21(5): 825-834, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-30607526

RESUMEN

PURPOSE: Lymph node (LN) metastasis is detected prior to distant metastasis in many types of cancer. Detecting early stage LN metastasis can improve treatment outcomes. However, there are few clinical imaging modalities capable of diagnosing metastatic LNs of clinical N0 status (i.e., before their volume increases) with high precision. Here, we report a new method for diagnosing metastatic LNs of clinical N0 status in a mouse model of LN metastasis. PROCEDURES: The method involved using intranodal lymphangiography with x-ray micro-computed tomography (micro-CT). Contrast agent was injected into an upstream LN to deliver it to a downstream LN, which was then removed and analyzed by micro-CT. RESULTS: We found that using an intranodal injection rate of 10-60 µl/min filled the lymphatic sinus of the downstream LN with contrast agent, although the accumulation of contrast agent in the upstream LN increased with a faster injection rate. Furthermore, breast cancer cells growing in the lymphatic sinus of the downstream LN (which was of clinical N0 status) impeded the flow of contrast agent from the upstream LN, resulting in areas deficient of contrast agent in the metastatic downstream LN. The formation of defect areas in the downstream LN manifested as a difference in position between the centroid of the entire LN area and the centroid of the region that filled with contrast agent. CONCLUSION: The present study indicates that intranodal lymphangiography with micro-CT has the potential to be used as a new method for diagnosing metastatic LNs of clinical N0 status.


Asunto(s)
Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Metástasis Linfática/diagnóstico por imagen , Linfografía , Microtomografía por Rayos X , Animales , Línea Celular Tumoral , Medios de Contraste/química , Inyecciones , Luciferasas/metabolismo , Ratones
18.
Oral Dis ; 25(1): 117-125, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30007097

RESUMEN

OBJECTIVE: We analysed the correlation between magnetic resonance images of the parotid and submandibular glands and the salivary flow rate in patients with Sjögren's syndrome. METHODS: We retrospectively reviewed magnetic resonance images (heterogeneous signal-intensity distribution and gland volume on T1- and fat-suppressed T2-weighted images, and multiple high-signal-intensity spots on magnetic resonance sialograms in the parotid and submandibular glands) obtained from 66 patients who were diagnosed with Sjögren's syndrome. We evaluated the relationship between these imaging features and their salivary flow rates in stimulated and unstimulated conditions. RESULTS: We found that as the disease progressed, both the heterogeneous signal-intensity distribution and the volumes of the parotid and the submandibular glands were significantly related to the stimulated and the unstimulated salivary flow rate. These imaging features were more highly correlated in assessments of the submandibular gland than in those of the parotid gland for both stimulated and unstimulated salivary flow rates. CONCLUSIONS: Magnetic resonance image features of heterogeneity and smaller volume in the submandibular gland are reliable for predicting hyposalivation related to the progression of Sjögren's syndrome.


Asunto(s)
Imagen por Resonancia Magnética , Síndrome de Sjögren/complicaciones , Glándula Submandibular/diagnóstico por imagen , Xerostomía/etiología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Glándula Parótida/diagnóstico por imagen , Estudios Retrospectivos , Adulto Joven
19.
Ultrasound Med Biol ; 44(8): 1818-1827, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29793853

RESUMEN

Conventional treatment of lymph node metastasis involves dissection of the tumor and regional lymph nodes, but this may cause activation of latent metastatic tumor cells. However, there are few reports on animal models regarding the activation of latent metastatic tumor cells and effective methods of treating activated tumor cells. Here, we report the use of a superselective drug delivery system in a mouse model of lung metastasis in which activated tumor cells are treated with doxorubicin-encapsulated liposomes (DOX-LP) and ultrasound. The axillary lymph node was injected with DOX-LP and exposed to ultrasound so that the released DOX would be delivered from the axillary lymph node to the metastatic lung via the subclavian vein, heart and pulmonary artery. The size of the DOX-LP was optimized to a diameter of 460 nm using indocyanine green-encapsulated liposomes, and the ultrasound intensity was 0.5 W/cm2. We found that compared with DOX or DOX-LP alone, the superselective drug delivery system was effective in the treatment of metastasis in both the lung and axillary lymph node. We anticipate that this superselective drug delivery system will be a starting point for the development of new techniques for treating lung metastasis in the clinical setting. Furthermore, the superselective drug delivery system may be used to screen novel drugs for the treatment of lung cancer and investigate the mechanisms of tumor cell activation after resection of a primary tumor or lymph nodes.


Asunto(s)
Doxorrubicina/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Liposomas , Neoplasias Pulmonares/patología , Metástasis Linfática , Terapia por Ultrasonido/métodos , Animales , Terapia Combinada , Modelos Animales de Enfermedad , Portadores de Fármacos , Ganglios Linfáticos , Ratones , Resultado del Tratamiento
20.
Eur Arch Otorhinolaryngol ; 275(6): 1613-1621, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29623392

RESUMEN

PURPOSE: To improve the diagnoses of the salivary gland tumors, a dynamic-enhanced MRI (dMRI) was investigated. METHODS: We conducted a retrospective chart review of 93 cases of salivary gland tumors. The histological diagnoses were obtained from all patients using a surgical specimen and/or an open biopsy specimen. The dMRI as well as fine-needle aspiration cytology (FNAC) and intraoperative frozen section (IFS) were analyzed. This study focused on the time-intensity curve (TIC) after injection, peak time (Tpeak), washout ratio (WR) as well as the gradient of enhancement and washout profile. RESULTS: The histological diagnoses included pleomorphic adenoma (PMA) in 53 cases, the Warthin tumors (WT) in 14 cases and malignant tumors (MT) in 26 cases. Incorrect diagnosis rate of FNAC and IFS were 5.2 and 8.3%, respectively. The TIC revealed differences among the three types of tumors. Tpeak as well as WR also revealed significant differences (p < 0.001). Tpeak were lower in order of WT, MT, PMA, respectively. WR of TICs at 30, 45 and 105 s after Tpeak were higher in order of WT, MT, PMA, respectively (p < 0.001). The gradient of increment and washout in the TIC curve was also an important parameter to distinguish the three types of tumors. In MT, the rapid enhancement pattern was found in high or intermediate histological grade tumors, whereas the slow enhancement pattern was exhibited in low grade tumors. CONCLUSIONS: Our findings indicate that using Tpeak and WR, it is possible to distinguish between WT, PMA and MT. Additionally, a rapid enhancement pattern may be a potential marker for these tumors.


Asunto(s)
Adenolinfoma/diagnóstico por imagen , Adenoma Pleomórfico/diagnóstico por imagen , Imagen por Resonancia Magnética , Neoplasias de las Glándulas Salivales/diagnóstico por imagen , Adenolinfoma/patología , Adenoma Pleomórfico/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia con Aguja Fina , Femenino , Secciones por Congelación , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Neoplasias de las Glándulas Salivales/patología , Adulto Joven
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