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BACKGROUND: Abnormal coronary microcirculation is linked to poor patient prognosis, so the aim of the present study was to assess the prognostic relevance of basal microvascular resistance (b-IMR) in patients without functional coronary stenosis.MethodsâandâResults: Analyses of 226 patients who underwent intracoronary physiological assessment of the left anterior descending artery included primary endpoints of all-cause death and heart failure, as well as secondary endpoints of cardiovascular death and atherosclerotic vascular events. During a median follow-up of 2 years, there were 12 (5.3%) primary and 21 (9.3 %) secondary endpoints. The optimal b-IMR cutoff for the primary endpoints was 47.1 U. Kaplan-Meier curve analysis demonstrated worse event-free survival of the primary endpoints in patients with a b-IMR below the cutoff (χ2=21.178, P<0.001). b-IMR was not significantly associated with the secondary endpoints (P=0.35). A low coronary flow reserve (CFR; <2.5) had prognostic value for both endpoints (primary endpoints: χ2=11.401, P=0.001; secondary endpoints: (χ2=6.015; P=0.014), and high hyperemic microvascular resistance (≥25) was associated only with the secondary endpoints (χ2=4.420; P=0.036). Incorporating b-IMR into a clinical model that included CFR improved the Net Reclassification Index and Integrated Discrimination Improvement for predicting the primary endpoints (P<0.001 and P=0.034, respectively). CONCLUSIONS: b-IMR may be a specific marker of the risk of death and heart failure in patients without functional coronary stenosis.
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Second-generation cryoballoon (CB) ablation is effective in achieving pulmonary vein (PV) isolation (PVI) in atrial fibrillation (AF) patients. The "crosstalk" (CST) phenomenon has been reported to reduce unnecessary applications during CB ablation. Nevertheless, it is unclear under what conditions the CST phenomenon occurs.To seek the predictors of the CST phenomenon during CB-guided PVI, CST phenomenon in achieving ipsilateral superior PVI during inferior PV ablation was analyzed in AF patients who underwent de novo ablation using CB. CB occlusion status and nadir balloon temperature (NT) were compared in these patients, and all ablated superior PVs were categorized into three groups according to the necessity of the touch up ablation and effectiveness of the phenomenon.Of 1082 superior PVs, 16, 40, and 1026 were classified into the CST success, CST failure, and control groups (unnecessary CST), respectively. The proportion of superior PVs ablated with complete occlusion using the CB was significantly higher in the CST success group than in the other two groups. The proportion of superior PVs ablated with NT ≤ -46°C was higher in the CST success group than in the CST failure group. The CST phenomenon was always observed if CB ablation of the superior PVs was performed with both complete occlusion and NT ≤ -46°C and was almost always ineffective if it did not meet these two criteria (sensitivity, 100%; specificity, 93%).Successful CST ablation was highly predicted if complete PV occlusion and NT ≤ -46°C during CB ablation of the superior PVs were achieved.
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Fibrilación Atrial/cirugía , Criocirugía/métodos , Sistema de Conducción Cardíaco/fisiopatología , Venas Pulmonares/cirugía , Anciano , Fibrilación Atrial/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Here we describe a rare case of mandibular cancer involving almost the entire attached gingiva in a 71-year-old man. First, marginal resection of the entire mandible was performed, followed by one-stage reconstruction comprising application of a split-thickness skin graft onto the wound. This resulted in good alveolar ridge morphology, allowing for a mandibular prosthesis to be installed soon postoperatively. Histopathological analysis revealed a well-differentiated squamous cell carcinoma extending throughout most of the resected attached gingiva, but no malignant features in the stumps. Furthermore, no infiltration into the jawbone was observed, and no vascular or lymphatic invasion or perineural infiltration. At 3 years postoperatively, the patient's clinical course has remained uneventful, with no recurrence or problems arising in the remaining mandible. The patient is also able to eat regularly using the mandibular prosthesis provided.
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Carcinoma de Células Escamosas , Encía , Anciano , Proceso Alveolar , Carcinoma de Células Escamosas/cirugía , Encía/cirugía , Humanos , Masculino , Mandíbula/cirugíaRESUMEN
The pathogenesis of thyroid lymphoepithelial cysts is controversial, and two hypotheses have been proposed, namely derivation from branchial-derived remnants or from squamous metaplasia of the follicular cells. The aim of this study was to clarify the pathogenesis of thyroid lymphoepithelial cysts. We performed pathological and immunohistochemical examination of 21 thyroid lymphoepithelial cysts, 13 non-neoplastic squamous metaplasia samples without thyroid carcinoma, 13 solid cell nests, and 14 lateral cervical cysts. On ultrasound, half of thyroid lymphoepithelial cysts were interpreted as calcified nodules regardless of no calcification. Thyroid lymphoepithelial cysts and squamous metaplasia tended to be located in the central and lower portions of the thyroid, while solid cell nests were located in the upper and central portions (p < 0.05). In 95.2% of patients with thyroid lymphoepithelial cysts and all patients with squamous metaplasia, lesions were histologically associated with chronic thyroiditis forming lymph follicles. Hashimoto's disease was serologically confirmed in 18 patients with lymphoepithelial cysts (85.7%) and 10 patients with squamous metaplasia (76.9%). Immunohistochemically, lymphoepithelial cysts showed nuclear positivity for PAX8, thyroid transcription factor 1, and p63. One lateral cervical cyst (7.1%) showed positive staining for PAX8, while solid cell nests were PAX8-negative. In three (14.3%) cases of thyroid lymphoepithelial cysts, squamous cells located on the superficial layer were focally and weakly positive for CEA. We concluded that thyroid lymphoepithelial cysts originate from follicular cells and are unrelated to solid cell nests and lateral cervical cysts arising from branchial-derived remnants.
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Quistes/patología , Enfermedades de la Tiroides/patología , Glándula Tiroides/patología , Adolescente , Adulto , Anciano , Niño , Preescolar , Quistes/diagnóstico por imagen , Femenino , Humanos , Masculino , Metaplasia/diagnóstico por imagen , Metaplasia/patología , Persona de Mediana Edad , Enfermedades de la Tiroides/diagnóstico por imagen , Glándula Tiroides/diagnóstico por imagen , Ultrasonografía , Adulto JovenRESUMEN
OBJECTIVE: The purpose of this study was to clarify the diagnostic significance of cytoplasmic lipid accumulation (CLIA) in the cribriform variant of papillary thyroid carcinoma (CV-PTC). METHODS: We performed a histological, immunohistochemical, and cytological examination of 35 CV-PTC cases at the Kuma Hospital. CLIA was defined as bubble-like multivacuolation in cytoplasm with distinct cell border. We also examined 100 conventional PTC (con-PTC) cases as controls. RESULTS: Histological analysis showed the presence of carcinoma cells with CLIA in 60.0% of CV-PTC and 5.0% of con-PTC cases. The vacuoles tended to distribute in the subnuclear portion of carcinoma cells showing papillary growth. They were positive for oil red O staining and adipophilin. The carcinoma cells without the vacuoles showed a subnuclear dot-like expression for adipophilin in CV-PTC cases, but not in the con-PTC cases. Cytological analysis showed CLIA in 17 (54.8%) of the 31 CV-PTC cases, but not in the con-PTC cases. CONCLUSION: This is the first study to report the presence of carcinoma cells with CLIA in CV-PTC. The subnuclear dot-like expression of adipophilin may be characteristic of CV-PTC. These findings might be related to degenerative changes occurring in CV-PTC.
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Adenocarcinoma/patología , Carcinoma Papilar/patología , Citoplasma/química , Lípidos/fisiología , Neoplasias de la Tiroides/patología , Adenocarcinoma/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Compuestos Azo/química , Carcinoma Papilar/clasificación , Carcinoma Papilar/diagnóstico , Citoplasma/ultraestructura , Femenino , Técnicas Histológicas , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Perilipina-2/química , Estudios Retrospectivos , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/clasificación , Neoplasias de la Tiroides/diagnóstico , Adulto JovenRESUMEN
Many cytological studies on medullary thyroid carcinoma (MTC) have been reported; however, such studies in large series of patients with MTC have not been performed. We investigated MTC at a single institution in Japan using fine-needle aspiration cytology (FNAC), and aimed to establish a preoperative diagnostic algorithm for MTC. FNAC was performed in 119 of 149 patients with MTC (79.9%) who ultimately underwent surgical resection. Moreover, 22 of 56 hereditary MTC (39.3%) were diagnosed preoperatively without FNAC by their high serum calcitonin levels or increased response to calcium stimulation (11 cases each), as well as RET mutation analysis. On FNAC, 76.5% of nodules were categorized as 'malignancy' or 'suspicious for malignancy'. The sensitivity and specificity of calcitonin measurement in aspiration needle wash-out fluid and in immunocytochemical staining for calcitonin were 96.3% and 92.3% respectively. We proposed an algorithm for preoperative diagnosis of MTC utilizing FNAC: When thyroid nodules are highly suspicious for MTC by their clinical and ultrasonographic features, serum calcitonin measurement with or without a calcium stimulation test is required. Furthermore, FNAC should be performed for patients who do not have those findings. When there is a possibility of MTC at the time of FNAC, calcitonin measurement using needle wash-out fluid is a reliable diagnostic tool. When MTC is suspected on cytological examination, immunocytochemical staining for calcitonin is useful for confirming MTC diagnosis.
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Carcinoma Neuroendocrino/patología , Neoplasias de la Tiroides/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia con Aguja Fina , Carcinoma Medular/congénito , Carcinoma Medular/genética , Carcinoma Medular/patología , Carcinoma Neuroendocrino/genética , Carcinoma Neuroendocrino/metabolismo , Niño , Citodiagnóstico , Análisis Mutacional de ADN , Femenino , Humanos , Inmunohistoquímica , Japón , Masculino , Persona de Mediana Edad , Neoplasia Endocrina Múltiple Tipo 2a/genética , Neoplasia Endocrina Múltiple Tipo 2a/patología , Proteínas Proto-Oncogénicas c-ret/genética , Estudios Retrospectivos , Sensibilidad y Especificidad , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Adulto JovenRESUMEN
Papillary thyroid carcinoma (PTC) with desmoid-type fibromatosis (DTF) is characterized by genetic alterations of the fibroblasts. PTC-DTF is extremely rare, and the reports on such cases have been sporadic. Immunohistochemical staining using the antibody for beta-catenin is useful in diagnosing the variant. This report aims to describe the clinical, pathological, and immunohistochemical findings in 14 cases of PTC-DTF and to clarify the diagnostic significance of the variant. The patients included 9 women and 5 men, with a mean age of 49.3 years. PTCs with focal DTF components and with extensive DTF components included 7 cases each. No significant differences were noted in terms of age, gender, and serum thyroglobulin levels between extensive and focal DTF cases. On aspiration cytology, 12 cases were reported as suspicious for malignancy or malignant, and schwannoma or fibroma was suggested in 1 case each. The DTF components were histologically classified into 4 types, namely, central (4 cases), peripheral (1 case), mixed (7 cases), and diffuse type (2 cases). The stromal components were consistent with those of DTF. Immunohistochemically, fibroblasts in the DTF components showed nuclear and cytoplasmic expression for beta-catenin in 12 cases. The features are observed even in cases in which stromal components focally exist. Neither carcinoma cells nor the fibroblasts with Ki-67 labeling index >5% were found in all cases. We agree that PTC with nodular fasciitis-like stroma should be renamed to PTC-DTF.
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Carcinoma Papilar/diagnóstico , Fascitis/diagnóstico , Fibromatosis Agresiva/diagnóstico , Glándula Tiroides/patología , Neoplasias de la Tiroides/diagnóstico , Nódulo Tiroideo/diagnóstico , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Biopsia con Aguja , Carcinoma Papilar/metabolismo , Carcinoma Papilar/patología , Carcinoma Papilar/cirugía , Diagnóstico Diferencial , Fascitis/metabolismo , Fascitis/patología , Fascitis/cirugía , Femenino , Fibroma/diagnóstico , Fibroma/metabolismo , Fibroma/patología , Fibroma/fisiopatología , Fibromatosis Agresiva/metabolismo , Fibromatosis Agresiva/patología , Fibromatosis Agresiva/cirugía , Estudios de Seguimiento , Hospitales Urbanos , Humanos , Inmunohistoquímica , Japón , Masculino , Persona de Mediana Edad , Neurilemoma/diagnóstico , Neurilemoma/metabolismo , Neurilemoma/patología , Neurilemoma/fisiopatología , Terminología como Asunto , Cáncer Papilar Tiroideo , Glándula Tiroides/metabolismo , Glándula Tiroides/cirugía , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Nódulo Tiroideo/metabolismo , Nódulo Tiroideo/patología , Nódulo Tiroideo/cirugía , Adulto Joven , beta Catenina/metabolismoRESUMEN
BACKGROUND: We previously developed a method for sentinel lymph node (SLN) mapping in non-small cell lung cancer (NSCLC), based on the magnetic force produced by a magnetite tracer already approved for use as a contrast material for magnetic resonance imaging. However, it is difficult to use that technique with video-assisted thoracic surgery (VATS) because the sensing element of the magnetometer is large and thick. The purpose of the present study was to develop a smaller, thinner VATS-compatible magnetometer. METHODS: The tracer employed was Ferucarbotran, a colloidal solution of superparamagnetic iron oxide coated with carbodextran. Fifteen patients with clinical stage I NSCLC were enrolled, and each received 1.6 mL of Ferucarbotran, injected intraoperatively at 5 points around the tumor. The magnetic force within the sampling lymph nodes was measured using the new VATS-compatible magnetometer. RESULTS: SLNs were detected in 11 (73.3%) of the 15 patients using the VATS-compatible magnetometer. The average number of SLNs identified per patient was 1.8 (range 0-4). No complications related to the SLN detection method were observed. CONCLUSIONS: The new VATS-compatible magnetometer appears to have substantial advantages over techniques using a radioisotope and our earlier magnetometer, as it can be inserted through the small VATS port site.
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Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Magnetometría/instrumentación , Biopsia del Ganglio Linfático Centinela/instrumentación , Biopsia del Ganglio Linfático Centinela/métodos , Cirugía Torácica Asistida por Video/instrumentación , Anciano , Diseño de Equipo , Óxido Ferrosoférrico/uso terapéutico , Humanos , Persona de Mediana EdadRESUMEN
Lymph node status is a key indicator of the best approach to treatment of invasive breast cancer. However, the accuracy with which lymph node metastasis is diagnosed is not currently satisfactory. New and more reliable methods that enable one to know who has a greater potential for lymph node metastasis would be highly desirable. We previously reported that lymph node involvement in esophageal and lung cancer may have a genetic component: C-reactive protein (CRP) 1846C>T genetic polymorphism. Here we examined the diagnostic value of CRP 1846C>T polymorphism for assessing the risk of lymph node metastasis in cases of invasive breast cancer. The study participants were 185 women with invasive breast cancer who underwent curative surgery with lymph node dissection. Using DNA from blood samples and polymerase chain reaction-restriction fragment length polymorphism, the utility of CRP genetic 1846C>T polymorphism (rs1205) for assessing the risk of lymph node metastasis was evaluated. Fifty-two (28 %) patients had lymph node metastasis. After the patients were divided into two groups based on their CRP 1846 genotypes (C/C+C/T and T/T), the clinical characteristics did not differ between the groups, but there was a significantly greater incidence of lymph node metastasis among patients in the T/T group. Moreover, the odds ratio for lymph node involvement in patients carrying the 1846 T/T genotype was more than 2.2 in multivariate logistic regression models. CRP genetic polymorphism may be a novel predictor of the risk of lymph node metastasis in invasive breast cancer.
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Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Proteína C-Reactiva/genética , Polimorfismo Genético , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Genotipo , Humanos , Metástasis Linfática , Persona de Mediana Edad , Invasividad NeoplásicaRESUMEN
BACKGROUND: Heat shock protein (Hsp) 90 is a key regulator of various oncogene products and cell-signaling molecules, while Hsp70 protects against heat-induced apoptosis. We previously described a system in which hyperthermia was produced using thermosensitive ferromagnetic particles (FMPs) with a Curie temperature (T c) of 43 °C to mediate automatic temperature control, and demonstrated its antitumor effect in a mouse melanoma model. In the present study, the antitumor effects of combining Hsp90 inhibitor (17DMAG) and Hsp70 inhibitor (quercetin) with FMP-mediated hyperthermia were examined. METHODS: Expressions of Hsp90/70 and Akt were evaluated using Western blotting in vitro. In an in vivo study, melanoma cells were subcutaneously injected into the backs of C57BL/6 mice. FMPs were then injected into the resultant tumors, and the mice were divided into groups treated with quercetin and/or 17DMAG with/without hyperthermia. When exposed to a magnetic field, the temperature of tissues containing FMPs increased and stabilized at the T c. The TUNEL method was used to determine whether hyperthermia induced apoptosis within tumors. RESULTS: In the group pretreated with hyperthermia + quercetin + 17DMAG, Akt expression was reduced in vitro, the incidence of apoptosis within tumors was greater, and tumor growth was significantly suppressed 20 days after FMP injection in vivo, compared with other treatment groups. The survival rates among tumor-bearing mice observed for a period of 40 days were significantly higher in the hyperthermia + quercetin + 17DMAG group. CONCLUSION: Combining Hsp90/70 inhibition with hyperthermia appears to increase their antitumor effects. Thus, the combination of FMP-mediated, self-regulating hyperthermia with Hsp90/70 inhibition has important implications for cancer treatment.
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Benzoquinonas/administración & dosificación , Proteínas HSP70 de Choque Térmico/biosíntesis , Proteínas HSP90 de Choque Térmico/biosíntesis , Hipertermia Inducida , Lactamas Macrocíclicas/administración & dosificación , Melanoma/tratamiento farmacológico , Quercetina/administración & dosificación , Animales , Apoptosis/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica , Proteínas HSP70 de Choque Térmico/antagonistas & inhibidores , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Humanos , Imanes , Melanoma/metabolismo , Melanoma/patología , RatonesRESUMEN
Surgical resection is the accepted standard of care for patients with non-small cell lung cancer (NSCLC). Several imaging modalities play central roles in the detection and staging of the disease. The aim of this review is to evaluate the utility of computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and PET/CT for NSCLC staging. Radiographic staging refers to the use of CT as a non-invasive diagnostic technique. However, while the vast majority of patients undergo only CT, CT is a notoriously inaccurate means of tumor and nodal staging in many situations. PET/CT clearly improves the staging, particularly nodal staging, compared to CT or PET alone. In addition, as a result of the increased soft-tissue contrast, MRI is superior to CT for distinguishing between tissue characteristics. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), which is a minimally invasive technique, also has pathological diagnostic potential. Extensive research and the resultant improvements in the understanding of genetics, histology, molecular biology and oncology are transforming our understanding of lung cancer, and it is clear that imaging modalities such as CT, MRI, PET and PET/CT will have an important role in its preoperative management. However, thoracic surgeons should also be aware of the limitations of these techniques.
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Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Cuidados Preoperatorios , Tomografía Computarizada por Rayos X , Carcinoma de Pulmón de Células no Pequeñas/secundario , Humanos , Neoplasias Pulmonares/patología , Estadificación de NeoplasiasRESUMEN
Here we describe two patients in whom prostheses were applied for flap protection after buccal mucosal incision. In the first case, the patient was a 65-year-old man with a diagnosis of buccal mucosa squamous cell carcinoma (T2N0M0). Left buccal mucosa squamous cell tumor resection and dermoplasty were performed, followed by alveolar ridge augmentation and buccal mucosal graft in the scar area. The carcinoma recurred, however, and left buccal mucosa carcinoma resection was performed, followed by reconstruction surgery using a free forearm flap. After a 12-week healing period, a molar support was constructed on the unaffected side and a protective prosthesis placed on the affected side. Training in ingestion and swallowing were given postoperatively. The patient in the second case was a 62-year-old woman with a diagnosis of buccal mucosa squamous cell carcinoma (T2N1M0). Right buccal mucosa carcinoma resection and supraomohyoid neck dissection were performed, followed by reconstruction surgery using a free forearm flap. A molar support was constructed on the unaffected side and a protective prosthesis placed on the affected side at 5 months postoperatively. Training was given in ingestion and swallowing postoperatively. The prostheses prevented bite wounds to the flaps in the affected areas due to jaw movement during swallowing or speaking. The postoperative courses were uneventful, and the average masticatory score was 92.5 (85, 100), not affecting daily life. The prostheses were placed after reconstruction surgery using free flaps after buccal mucosa squamous cell carcinoma resection. Dysphasia recovered to the preoperative level by dysphasia and pronunciation training in both cases. The postoperative prognosis was favorable, with the prosthesis preventing damage to the flap.
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Carcinoma de Células Escamosas/cirugía , Colgajos Tisulares Libres/trasplante , Neoplasias de la Boca/cirugía , Procedimientos de Cirugía Plástica/instrumentación , Férulas (Fijadores) , Anciano , Deglución/fisiología , Diseño de Equipo , Femenino , Estudios de Seguimiento , Humanos , Masculino , Masticación/fisiología , Persona de Mediana Edad , Terapia Miofuncional/métodos , Recurrencia Local de Neoplasia/cirugía , Procedimientos de Cirugía Plástica/métodos , Habla/fisiologíaRESUMEN
The Japanese Breast Cancer Society (JBCS) Clinical Practice Guidelines for systemic treatment of breast cancer were updated to the 2022 edition through a process started in 2018. The updated guidelines consist of 12 background questions (BQs), 33 clinical questions (CQs), and 20 future research questions (FRQs). Multiple outcomes including efficacy and safety were selected in each CQ, and then quantitative and qualitative systematic reviews were conducted to determine the strength of evidence and strength of recommendation, which was finally determined through a voting process among designated committee members. Here, we describe eight selected CQs as important updates from the previous guidelines, including novel practice-changing updates, and recommendations based on evidence that has emerged specifically from Japanese clinical trials.
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Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Pueblos del Este de Asia , JapónRESUMEN
In May 2019, the World Health Assembly, in an unprecedented move, endorsed the inclusion of traditional medicine in the International Classification of Diseases, 11th Revision. In Japan, traditional medicine (known as Kampo) is regulated by the government and prescribed by over 90% of physicians along with modern medicine under the national health insurance system. Although Kampo education must be included in Japan's core medical curricula, there are significant challenges to implementation. In the educational context, the flipped classroom teaching method has received considerable attention in recent years. This study developed a Kampo e-learning program and verified the effectiveness of a flipped classroom using Kampo e-learning. The Kampo e-learning Committee determined three courses and assigned an administrator for each. The administrators appointed lecturers who developed Kampo e-learning lessons. Physicians, pharmacists, medical students, and pharmacy students were asked to participate in the e-learning program, and their comments and suggestions were collected after program completion. The flipped classroom was evaluated by implementing Kampo e-learning in the Kampo session with fourth-year students at Keio University School of Medicine in Japan. Seven courses were created, including four based on volunteer suggestions. The 'Systematic Kampo Curricula' featured 88 lessons developed by 54 Kampo specialists. Out of 118 fourth-year medical students who participated in the flipped classroom, 113 registered for the Kampo e-learning program, 100 attended the session, and 88 answered the post-session questionnaire. Among the students who answered the questionnaire, 86.4% were satisfied with the flipped classroom, 79.5% replied that the program made them understand Kampo and 80.7% stated that it should be adopted. The flipped classroom using Kampo e-learning program was shown to be attractive in one medical school. Further expanded study is necessary in the near future to reveal the usefulness of the flipped classroom of Kampo learning.
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Educación a Distancia , Personal de Salud/educación , Medicina Kampo/métodos , Curriculum , Humanos , Internet , Japón , Aprendizaje , Aprendizaje Basado en Problemas/métodos , UniversidadesRESUMEN
We investigated the seismological structure beneath the equatorial Melanesian region, where is tectonically unique because an immense oceanic plateau, a volcanic chain and subduction zones meet. We conducted a multi-frequency P-wave tomography using data collected from an approximately 2-year-long seismic experiment around the Ontong Java Plateau (OJP). High-velocity anomalies were revealed beneath the center of the OJP at a depth of ~ 150 km, the middle-eastern edge of the OJP at depths of 200-300 km, and in the mantle transition zone beneath and around the OJP; low-velocity anomalies were observed along the Caroline volcanic island chain above 450 km depth. These anomalies are considered to be associated with the thick lithosphere of the OJP, remnant dipping Pacific slab, stagnant Pacific slab, and a sheet-like upwelling. The broad stagnant slab was formed due to rapid trench retreat from 48 to 25 Ma until when the OJP with thick lithosphere collided with a subduction boundary of the Pacific and Australian plates. This collision triggered slab breakoff beneath the arc where the dipping slab remained. The stagnant Pacific slab in the mantle transition zone restricted the plume upwelling from the lower mantle causing sheet-like deformed upwelling in the upper mantle.
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BACKGROUND: We have developed genetic methods in zebrafish by using the Tol2 transposable element; namely, transgenesis, gene trapping, enhancer trapping and the Gal4FF-UAS system. Gene trap constructs contain a splice acceptor and the GFP or Gal4FF (a modified version of the yeast Gal4 transcription activator) gene, and enhancer trap constructs contain the zebrafish hsp70l promoter and the GFP or Gal4FF gene. By performing genetic screens using these constructs, we have generated transgenic zebrafish that express GFP and Gal4FF in specific cells, tissues and organs. Gal4FF expression is visualized by creating double transgenic fish carrying a Gal4FF transgene and the GFP reporter gene placed downstream of the Gal4-recognition sequence (UAS). Further, the Gal4FF-expressing cells can be manipulated by mating with UAS effector fish. For instance, when fish expressing Gal4FF in specific neurons are crossed with the UAS:TeTxLC fish carrying the tetanus neurotoxin gene downstream of UAS, the neuronal activities are inhibited in the double transgenic fish. Thus, these transgenic fish are useful to study developmental biology and neurobiology. DESCRIPTION: To increase the usefulness of the transgenic fish resource, we developed a web-based database named zTrap http://kawakami.lab.nig.ac.jp/ztrap/. The zTrap database contains images of GFP and Gal4FF expression patterns, and genomic DNA sequences surrounding the integration sites of the gene trap and enhancer trap constructs. The integration sites are mapped onto the Ensembl zebrafish genome by in-house Blat analysis and can be viewed on the zTrap and Ensembl genome browsers. Furthermore, zTrap is equipped with the functionality to search these data for expression patterns and genomic loci of interest. zTrap contains the information about transgenic fish including UAS reporter and effector fish. CONCLUSION: zTrap is a useful resource to find gene trap and enhancer trap fish lines that express GFP and Gal4FF in desired patterns, and to find insertions of the gene trap and enhancer trap constructs that are located within or near genes of interest. These transgenic fish can be utilized to observe specific cell types during embryogenesis, to manipulate their functions, and to discover novel genes and cis-regulatory elements. Therefore, zTrap should facilitate studies on genomics, developmental biology and neurobiology utilizing the transgenic zebrafish resource.
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Animales Modificados Genéticamente/genética , Bases de Datos Genéticas , Elementos de Facilitación Genéticos , Pez Cebra/genética , Animales , Elementos Transponibles de ADN/genética , Regulación del Desarrollo de la Expresión Génica , Genes Reporteros , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Programas Informáticos , Transgenes , Pez Cebra/embriología , Pez Cebra/crecimiento & desarrolloRESUMEN
Heat shock protein (Hsp) 90 is a key regulator of a variety of oncogene products and cell-signaling molecules, and the therapeutic benefit of its inhibition in combination with radiation or chemotherapy has been investigated. In addition, hyperthermia has been used for many years to treat various malignant tumors. We previously described a system in which hyperthermia was induced using thermosensitive ferromagnetic particles (FMP) with a Curie temperature (Tc = 43 degrees C) low enough to mediate automatic temperature control, and demonstrated its antitumor effect in a mouse melanoma model. In the present study, we examined the antitumor effects of combining a Hsp90 inhibitor (geldanamycin; GA) with FMP-mediated hyperthermia. In cultured B16 melanoma cells, GA exerted an antitumor effect by increasing the cells' susceptibility to hyperthermia and reducing expression of Akt. In an in vivo study, melanoma cells were subcutaneously injected into the backs of C57BL/6 mice. FMP were then injected into the resultant tumors, and the mice were divided into four groups: group I, no treatment (control); group II, one hyperthermia treatment; group III, GA alone; and group IV, GA with hyperthermia. When exposed to a magnetic field, the temperature of tissues containing FMP increased and stabilized at the Tc. In group IV, complete regression of tumors was observed in five of nine mice (56%), whereas no tumor regression was seen in groups I-III. Our findings suggest that inhibition of Hsp90 with hyperthermia increases its antitumor effect. Thus, the combination of FMP-mediated, self-regulating hyperthermia with Hsp90 inhibition has important implications for the treatment of cancer.
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Compuestos Férricos/uso terapéutico , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Hipertermia Inducida/métodos , Melanoma Experimental/terapia , Neoplasias Cutáneas/terapia , Animales , Antibióticos Antineoplásicos/administración & dosificación , Benzoquinonas/administración & dosificación , Western Blotting , Línea Celular Tumoral , Terapia Combinada , Femenino , Etiquetado Corte-Fin in Situ , Lactamas Macrocíclicas/administración & dosificación , Melanoma Experimental/metabolismo , Ratones , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
Hyperthermia has been used for many years to treat a variety of malignant tumors. The Curie temperature (Tc) is a transition point at which magnetic materials lose their magnetic properties, causing a cessation of current and thus heat production. The Tc enables automatic temperature control throughout a tumor as a result of the self-regulating nature of the thermosensitive material. We have developed a method of magnetically-induced hyperthermia using thermosensitive ferromagnetic particles (FMPs) with low Tc (43 degrees C), enough to mediate automatic temperature control. B16 melanoma cells were subcutaneously injected into the backs of C57BL/6 mice, after which tumors were allowed to grow to 5 mm in diameter. FMPs were then injected into the tumors, and the mice were divided into three groups: group I (no hyperthermia, control); group II (one hyperthermia treatment); and group III (hyperthermia twice a week for 4 weeks). When exposed to a magnetic field, the FMPs showed a sharp rise in heat production, reaching the Tc in tissue within 7 min, after which the tissue temperature stabilized at approximately the Tc. In groups I and II, all mice died within 30-45 days. In group III, however, 6 of 10 mice remained alive 120 days after beginning treatment. Our findings suggest that repeated treatment with magnetically-induced self-regulating hyperthermia, mediated by FMPs with a low Tc, is an effective means of suppressing melanoma growth. A key advantage of this hyperthermia system is that it is minimally invasive, requiring only a single injection for repeated treatments with automatic temperature control.
Asunto(s)
Compuestos Férricos/uso terapéutico , Hipertermia Inducida/métodos , Magnetismo/uso terapéutico , Melanoma Experimental/terapia , Neoplasias Cutáneas/terapia , Animales , Modelos Animales de Enfermedad , Hipertermia Inducida/instrumentación , Ratones , Ratones Endogámicos C57BL , TemperaturaRESUMEN
BACKGROUND: Regenerating gene I alpha (REG1A) is a growth factor known to affect pancreatic islet beta cells. Although REG1A expression has also been observed in various malignant tumors, the correlation between REG1A expression and the clinicopathological characteristics of breast cancer and patient prognosis has not been evaluated. METHODS: Resected breast cancer tissues obtained at surgery from 150 breast cancer patients was stained with anti-REG1A antibody, after which the relative area occupied by stained tumor cells was evaluated under a light microscope and correlated with known clinicopathological factors. RESULTS: Whereas tumor cells were frequently stained with anti-REG1A antibody, cells from normal breast tissue were not stained. REG1A expression in tumors of breast cancer patients with HER2-positive disease was higher than those with HER2-negative disease (P = .0009). The 10-year disease-specific survival rate among patients with lower levels of REG1A was significantly better than among those with higher levels (P = .0002 by log rank test). Multivariate Cox proportional hazard analyses revealed REG1A (hazard ratio, 2.07; 95% confidence interval, 1.93 to 11.29; P = .0005) and axillary lymph node status (hazard ratio, 4.44; 95% confidence interval, 1.52 to 11.29; P = .0003) to be independent factors affecting the 10-year disease-specific survival rate. CONCLUSION: High levels of REG1A expression within tumors are an independent predictor of poor prognosis in patients with breast cancer.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Litostatina/metabolismo , Adulto , Anciano , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Tasa de SupervivenciaRESUMEN
PURPOSE: The aim of this study was to investigate the ultrasound characteristics and clinical significance of slightly hyperechoic lesions, referred to as phantom nodules, in the perithyroidal area in patients. MATERIALS AND METHODS: A total of 128 patients who underwent thyroidectomy with central neck lymph node dissection at Kuma Hospital in Hyogo, Japan were included in the study. We detected 16 phantom nodules during preoperative ultrasound examinations, defined as slightly hyperechoic masses located in the perithyroidal areas, in 13 of these 128 patients (10.2%; mean age: 55.6 years, range: 36-75 years). RESULTS: All phantom nodules were located in the caudal region of the thyroid gland, and the mean maximum dimension was 7.2 mm. 12 of the 16 nodules were round or oval, while the remaining 4 were fusiform and molded by the surrounding tissue. All nodules were well-defined, solid, homogeneous, hyperechoic masses. No speckled echo pattern, internal linear echo, or vascular flow signal was observed. All 4 nodules subjected to histological examination were composed of ectopic thymic tissue. In 2 of these 4, the parenchyma was severely involuted and almost entirely replaced by adipose tissue. CONCLUSION: To the best of our knowledge, this is the first report wherein some of the detected hyperechoic perithyroidal masses were composed of ectopic thymic tissue, and some were primarily composed of adipose tissue that completely replaced involuted ectopic thymic tissue. The results of the study suggest that these so-called phantom nodules are clinically insignificant and do not require fine needle aspiration cytology or further investigation.