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1.
Proc Natl Acad Sci U S A ; 120(44): e2307926120, 2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37871226

RESUMEN

Triplet dynamic nuclear polarization (triplet-DNP) is a technique that can obtain high nuclear polarization under moderate conditions. However, in order to obtain practically useful polarization, large single crystals doped with a polarizing agent must be strictly oriented with respect to the magnetic field to sharpen the electron spin resonance (ESR) spectra, which is a fatal problem that prevents its application to truly useful biomolecular targets. Instead of this conventional physical approach of controlling crystal orientation, here, we propose a chemical approach, i.e., molecular design of polarizing agents; pentacene molecules, the most typical triplet-DNP polarizing agent, are modified so as to make the triplet electron distribution wider and more isotropic without loss of the triplet polarization. The thiophene-modified pentacene exhibits a sharper and stronger ESR spectrum than the parent pentacene, and state-of-the-art quantum chemical calculations revealed that the direction of the spin polarization is altered by the modification with thiophene moieties and the size of D and E parameters are reduced from parent pentacene due to the partial delocalization of spin densities on the thiophene moieties. The triplet-DNP with the new polarizing agent successfully exceeds the previous highest 1H polarization of glassy materials by a factor of 5. This demonstrates the feasibility of a polarizing agent that can surpass pentacene, the best polarizing agent for more than 30 y since triplet-DNP was first reported, in the unoriented state. This work provides a pathway toward practically useful high nuclear polarization of various biomolecules by triplet-DNP.

2.
J Orthop Sci ; 29(1): 207-216, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36628847

RESUMEN

BACKGROUND: Recently, various types of engineered autologous chondrocyte implantation (ACI) have been developed. Atelocollagen-associated ACI (A-ACI) is the only ACI procedure covered by Japanese Health Insurance since 2013. The indications of the A-ACI are traumatic cartilage defects and osteochondral dissecans (OCD) for knee joints. PURPOSE: To evaluate midterm clinical results after A-ACI for the treatment for full-thickness cartilage defects of the knee. METHODS: Thirteen consecutive patients who underwent A-ACI between 2014 and 2018 had been prospectively enrolled in this study. There were 11 men and 2 women with a mean age of 34 years at the time of surgery. The causes of the cartilage defect were trauma in 10 knees and OCD in 3 knees. The total number of lesions was 15, which were comprised of the medial femoral condyle in 5 knees, the lateral femoral condyle in 5 knees, and the femoral trochlea in 5 knees. The mean size of the lesion was 5.3 cm2. Each knee was clinically and radiologically evaluated preoperatively and postoperatively. RESULTS: The mean Lysholm score improved significantly from 74.0 points to 94.0 points (p = 0.008) and each subscale in Knee injury and Osteoarthritis Outcome Score improved significantly (p < 0.001) at the mean final follow-up period of 51 months (range, 36-84 months). The magnetic resonance observation of cartilage repair tissue 2.0 score at the mean follow-up of 38 months was significantly higher than that at 2 months postoperatively (p = 0.014). According to the International Cartilage Repair Society (ICRS) grading scale, 3 knees were graded as normal, 3 knees as nearly normal, and 1 knee as severely abnormal in second-look arthroscopic evaluation at a mean of 22 months (range, 8-41 months) after A-ACI. CONCLUSION: The present study showed a significant subjective and objective clinical improvement in the A-ACI for large cartilage defects of the knee at a mean follow-up of 51 months (range, 36-84 months).


Asunto(s)
Enfermedades de los Cartílagos , Cartílago Articular , Procedimientos Ortopédicos , Masculino , Humanos , Femenino , Adulto , Condrocitos/trasplante , Cartílago Articular/diagnóstico por imagen , Cartílago Articular/cirugía , Cartílago Articular/lesiones , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Procedimientos Ortopédicos/métodos , Enfermedades de los Cartílagos/diagnóstico por imagen , Enfermedades de los Cartílagos/cirugía , Trasplante Autólogo/métodos , Estudios de Seguimiento
3.
Dev Growth Differ ; 65(1): 48-55, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36517457

RESUMEN

Myosin heavy chains (MyHCs), which are encoded by myosin heavy chain (Myh) genes, are the most abundant proteins in myofiber. Among the 11 sarcomeric Myh isoform genes in the mammalian genome, seven are mainly expressed in skeletal muscle. Myh genes/MyHC proteins share a common role as force producing units with highly conserved sequences, but have distinct spatio-temporal expression patterns. As such, the expression patterns of Myh genes/MyHC proteins are considered as molecular signatures of specific fiber types or the regenerative status of mammalian skeletal muscles. Immunohistochemistry is widely used for identifying MyHC expression patterns; however, this method is costly and is not ideal for whole-mount samples, such as embryos. In situ hybridization (ISH) is another versatile method for the analysis of gene expression, but is not commonly applied for Myh genes, partly because of the highly homologous sequences of Myh genes. Here we demonstrate that an ISH analysis with the untranslated region (UTR) sequence of Myh genes is cost-effective and specific method for analyzing the Myh gene expression in whole-mount samples. Digoxigenin (DIG)-labeled antisense probes for UTR sequences, but not for protein coding sequences, specifically detected the expression patterns of respective Myh isoform genes in both embryo and adult skeletal muscle tissues. UTR probes also revealed the isoform gene-specific polarized localization of Myh mRNAs in embryonic myofibers, which implied a novel mRNA distribution mechanism. Our data suggested that the DIG-labeled UTR probe is a cost-effective and versatile method to specifically detect skeletal muscle Myh genes in a whole-mount analysis.


Asunto(s)
Cadenas Pesadas de Miosina , ARN , Animales , Cadenas Pesadas de Miosina/genética , Cadenas Pesadas de Miosina/metabolismo , Sondas ARN/metabolismo , Digoxigenina/metabolismo , Regiones no Traducidas , Músculo Esquelético/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Perfilación de la Expresión Génica , Hibridación in Situ , Mamíferos/metabolismo
4.
Jpn J Clin Oncol ; 52(6): 531-538, 2022 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-35325167

RESUMEN

Nuclear protein of the testis (NUT) midline carcinoma (NMC) is a rare tumor that typically presents in the head, neck, and chest region. NMC is characterized by rearrangement of the NUTM1 gene. It mainly affects children and young adults and is rapidly progressive and lethal. Reportedly, the prognoses of NMCs of the head and neck improve following aggressive initial surgical resection +/- postoperative chemoradiotherapy (CRT) or radiotherapy (RT). However, as NMC of the thorax was identified later, treatments to improve its prognosis are yet to be identified. Our review reveals that NMC is an extremely rare cancer, and most patients remain undiagnosed. Furthermore, this review outlines the clinical characteristics of NMC of the thorax and the prospects for its treatment.


Asunto(s)
Carcinoma , Neoplasias Testiculares , Carcinoma/patología , Quimioradioterapia , Niño , Humanos , Masculino , Proteínas Nucleares/genética , Proteínas de Fusión Oncogénica/genética , Neoplasias Testiculares/genética , Neoplasias Testiculares/terapia , Tórax , Adulto Joven
5.
J Clin Apher ; 36(3): 313-321, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33325084

RESUMEN

OBJECTIVE: To evaluate the efficacy and safety of direct hemoperfusion using a polymyxin B-immobilized polystyrene column (PMX-DHP) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive pneumonia patients. METHODS: This study was a case series conducted at a designated infectious diseases hospital. Twelve SARS-CoV-2-positive patients with partial pressure of arterial oxygen/percentage of inspired oxygen (P/F) ratio < 300 were treated with PMX-DHP on two consecutive days each during hospitalization. We defined day 1 as the first day when PMX-DHP was performed. PMX-DHP efficacy was assessed on days 7 and 14 after the first treatment based on eight categories. Subsequently, improvement in P/F ratio and urinary biomarkers on days 4 and 8, malfunctions, and ventilator and extracorporeal membrane oxygenation avoidance rates were also evaluated. RESULTS: On day 14 after the first treatment, disease severity decreased in 58.3% of the patients. P/F ratio increased while urine ß2-microglobulin decreased on days 4 and 8. Cytokine measurement pre- and post-PMX-DHP revealed decreased levels of interleukin-6 and the factors involved in vascular endothelial injury, including vascular endothelial growth factor. Twenty-two PMX-DHPs were performed, of which seven and five PMX-DHPs led to increased inlet pressure and membrane coagulation, respectively. When the membranes coagulated, the circuitry needed to be reconfigured. Circuit problems were usually observed when D-dimer and fibrin degradation product levels were high before PMX-DHP. CONCLUSIONS: Future studies are expected to determine the therapeutic effect of PMX-DHP on COVID-19. Because of the relatively high risk of circuit coagulation, coagulation capacity should be assessed beforehand.


Asunto(s)
COVID-19/terapia , Hemoperfusión/instrumentación , Hemoperfusión/métodos , Polimixina B/química , Poliestirenos/química , Adulto , Anciano , Anciano de 80 o más Años , Arterias/metabolismo , Biomarcadores/orina , Análisis de los Gases de la Sangre , Citocinas/sangre , Endotelio Vascular/metabolismo , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Oxígeno/metabolismo , Respiración Artificial , Estudios Retrospectivos , Riesgo , Microglobulina beta-2/orina
6.
Rheumatology (Oxford) ; 59(7): 1734-1742, 2020 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-31925431

RESUMEN

OBJECTIVE: Rapidly progressive interstitial lung disease (RPILD) is a major cause of death in patients with DM. Although clinically amyopathic DM (CADM) represents risk for RPILD, the incidence rate of RPILD in patients with CADM varies widely. Whole-body (WB) MRI can reveal involvement of systemic muscle and myofascia. The objective of this study was to explore the risk factors for RPILD in patients with DM using WB-MRI. METHODS: This retrospective study comprised 41 patients with DM who underwent WB-MRI before the initiation of treatment in our hospital. Muscular and myofascial signals were scored on 42 muscular groups. The myofascia/muscle ratio was calculated and used to define the relevance of myofascia-dominant involvement. RPILD was defined as worsening of dyspnoea, hypoxaemia and radiographic ILD/fibrosis within 3 months from the onset of respiratory symptoms. RESULTS: Among the 41 patients, 17 had CADM and 30 had ILD, including 10 patients with RPILD. All patients including those with CADM showed abnormal signal intensity in both muscle and myofascia (median score: 15 and 23, respectively). Muscle signal scores positively correlated with the serum creatine kinase level (r = 0.714; P< 0.001). Patients with RPILD showed a significantly higher myofascia/muscle ratio than those without RPILD (1.929 vs 1.200; P= 0.027). Logistic regression analysis identified higher myofascia/muscle ratio as independent risk factors for developing RPILD. CONCLUSION: Myofascia-dominant involvement was defined and appreciated in patients with DM using WB-MRI. This may be one of the risk factors for RPILD.


Asunto(s)
Dermatomiositis/diagnóstico por imagen , Fascia/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Músculo Esquelético/diagnóstico por imagen , Adulto , Dermatomiositis/complicaciones , Progresión de la Enfermedad , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/etiología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Imagen de Cuerpo Entero
7.
Chemistry ; 25(36): 8528-8542, 2019 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-30882926

RESUMEN

Iriomoteolide-2a is a marine macrolide metabolite isolated from a cultured broth of the benthic dinoflagellate Amphidinium sp. HYA024 strain. This naturally occurring substance was reported to show remarkable cytotoxic activity against human cancer cell lines HeLa and DG-75 and in vivo antitumor activity against murine leukemia P388 cell line. Herein, the total synthesis, stereochemical revision, and biological assessment of iriomoteolide-2a are reported in detail. Total synthesis of the proposed structure 1 of iriomoteolide-2a featured a late-stage convergent assembly of three components by a Suzuki-Miyaura coupling, an esterification, and a ring-closing metathesis. However, the NMR data of synthetic 1 were not identical to those of the natural product. Careful analysis of the NMR data of the authentic material and synthesis/NMR analysis of appropriately designed model compounds led to consideration of four possible stereoisomers 2-5 as candidates for the correct structure. Accordingly, total syntheses of 2-5 were achieved by taking advantage of the convergent strategy, and comparison of the NMR spectra of synthetic 2-5 with those of the natural product led to the conclusion that 5 shows the correct relative configuration of iriomoteolide-2a. The absolute configuration of this natural product was finally established through chiral HPLC analysis of synthetic 5/ent-5 with the authentic sample. The antiproliferative activity of the synthetic compounds was assessed against HeLa and A549 cells to show that, in contrast to expectation, synthetic 5 and ent-5 were only marginally active in these cell lines. This work clearly underscores the vital role of total synthesis in the establishment of the structure and biological activity of natural products.


Asunto(s)
Productos Biológicos/síntesis química , Macrólidos/química , Productos Biológicos/química , Productos Biológicos/toxicidad , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Dinoflagelados/química , Dinoflagelados/metabolismo , Esterificación , Humanos , Macrólidos/síntesis química , Macrólidos/toxicidad , Espectroscopía de Resonancia Magnética , Conformación Molecular , Estereoisomerismo
8.
BMC Musculoskelet Disord ; 20(1): 481, 2019 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-31656183

RESUMEN

BACKGROUND: To perform medial open-wedge high tibial osteotomy (OWHTO), surgeons expose the medial-proximal tibia by releasing or cutting the superficial layer of the medial collateral ligament (sMCL). Biomechanically, the sMCL provides primary restraint against valgus forces. Therefore, any release of the sMCL can cause valgus instability of the knee joint. The purpose of this study was to assess valgus laxity after release of the medial structure of the knee during OWHTO. METHODS: Between 2009 and 2015, 84 consecutive patients (93 knees) who underwent OWHTO using a locking plate were enrolled in this study. All patients underwent radiological examinations before surgery, during surgery, 1 year after surgery, and after plate removal to objectively assess valgus laxity. The medial joint space (MJS) and the joint line convergence angle (JLCA) of the knee were evaluated using quantitative valgus stress radiography. Clinical evaluation was performed 2 years after surgery. RESULTS: The mean functional knee score improved significantly, from 65.5 to 91.1 points (p < 0.0001). The mechanical axis percentage shifted to pass through a point 69.7% lateral from the medial edge of the tibial plateau. The MJS and JLCA increased significantly during OWHTO surgery (11.0 mm, 7.4 °, p < 0.0001). However, no significant differences were noted in the MJS and JLCA among preoperative, 1-year postoperative periods and after plate removal. CONCLUSION: Valgus laxity was significantly greater after release of the sMCL. However, no significant differences were noted in valgus laxity in preoperative, 1-year postoperative periods and after plate removal. Complete release of the sMCL did not cause postoperative valgus laxity after OWHTO surgery. TRIAL REGISTRATION: Trial registration number: No.012-0360.


Asunto(s)
Inestabilidad de la Articulación/diagnóstico , Articulación de la Rodilla/cirugía , Osteoartritis de la Rodilla/cirugía , Osteotomía/efectos adversos , Tibia/cirugía , Adulto , Anciano , Placas Óseas , Femenino , Humanos , Inestabilidad de la Articulación/etiología , Articulación de la Rodilla/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Osteotomía/instrumentación , Osteotomía/métodos , Periodo Posoperatorio , Estudios Prospectivos
9.
Angew Chem Int Ed Engl ; 57(14): 3801-3805, 2018 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-29385300

RESUMEN

Total syntheses of the proposed and correct structures of iriomoteolide-2a, a cytotoxic marine macrolide natural product with an unusual 23-membered macrolactone skeleton, have been accomplished for the first time. The synthesis of the correct structure involves an asymmetric epoxidation/diepoxide cyclization cascade for the construction of the bis(tetrahydrofuran) moiety, a Suzuki-Miyaura coupling for the fragment assembly, and a ring-closing metathesis for the closure of the macrocyclic backbone. In addition, the original stereochemical assignment of iriomoteolide-2a was revised.

10.
Surg Today ; 47(9): 1104-1110, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28229300

RESUMEN

PURPOSE: Pancreatic neuroendocrine tumor (PNET) is relatively rare and has a generally better prognosis than does pancreatic cancer. However, as its prognosis in patients with lymph node metastasis (LNM) is unclear, lymph node dissection for PNET is controversial. Our study aimed to clarify the significance of LNM in PNET. METHODS: We retrospectively examined 83 PNET patients who underwent pancreatic resections with lymph node dissection at Kumamoto University Hospital, Saiseikai Kumamoto Hospital, and Kumamoto Regional Medical Center from April 2001 to December 2014. Their clinicopathological parameters were analyzed by the absence or presence of LNM, and with regard to the disease-free survival (DFS) and overall survival (OS). A predictive score of LNM was also made using the age, tumor size, primary tumor location, and tumor function. RESULTS: Although the 5-year OS was 74.8% for LNM+ and 94.6% for LNM- (P = 0.002), LNM was not an independent risk factor for the OS in a multivariate analysis. However, tumors larger than 1.8 cm were found to be an independent prognostic factor, and the cut-off value for the predictive score was 1.69. CONCLUSIONS: Although LNM was not an independent prognostic factor, lymph node dissection is recommended for patients whose predictive score is larger than 1.69.


Asunto(s)
Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/cirugía , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Masculino , Persona de Mediana Edad , Pancreatectomía/métodos , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven
11.
Mod Rheumatol ; 27(6): 953-960, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28121200

RESUMEN

OBJECTIVES: To evaluate the scoring of whole-body magnetic resonance imaging (WBMRI) for efficacy assessment in rheumatoid arthritis (RA) patients receiving biological disease-modifying anti-rheumatic drugs (bDMARDs). METHODS: Thirty consecutive RA patients receiving bDMARDs were included in this retrospective study. Contrast WBMRI was performed before and 1 year after bDMARDs initiation. RESULTS: At baseline, mean age was 57.1 years and mean disease duration was 3.0 years. Median disease activity score in 28 joints improved from 5.1 to 2.1. Treatment with bDMARDs improved mean whole-body synovitis score from 31.2 to 23.2 and median whole-body bone-edema score from 11 to 3. Whole-body bone-erosion score improved in seven patients and deteriorated in 17 patients. Logistic regression analysis identified whole-body synovitis score as a poor prognostic factor for whole-body bone-erosion progression. Bone-edema score in individual bones was identified as a poor prognostic factor for the progression of bone-erosion. Changes in hand synovitis score correlated with those of other joints, but neither changes in bone-edema nor erosion score of hands correlated with those of other joints in WBMRI. CONCLUSIONS: WBMRI scoring may be a novel useful tool to evaluate the efficacy of anti-rheumatic drugs, as well as a potential predictor of joint prognosis, in patients with RA.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/diagnóstico por imagen , Imagen por Resonancia Magnética , Adulto , Anciano , Artritis Reumatoide/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Retrospectivos
12.
Int J Clin Oncol ; 21(2): 310-319, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26338271

RESUMEN

BACKGROUND: Major hepatectomy is associated with significant morbidity and mortality rates, particularly in patients aged more than 70 years. This study assessed whether physical indicators, such as sarcopenia and visceral fat amount, could predict morbidity and mortality after major hepatectomy. METHODS: The study enrolled 144 patients who underwent curative major hepatectomy. Skeletal muscle and visceral fat amount at the third lumbar vertebra (L3) in the inferior direction were quantified using enhanced computed tomography scans. The patients were divided into two subgroups, with and without sarcopenia, based on median skeletal muscle mass in men and women (43.2 cm(2)/m(2) in men; 35.3 cm(2)/m(2) in women). RESULTS: The study included 108 men and 36 women, with median skeletal muscle tissue of 43.2 and 35.3 cm(2)/m(2), respectively. The mortality rate was significantly higher in patients with than without sarcopenia [seven cases (9.7 %), one case (1.4 %), respectively; P = 0.021], whereas liver-related morbidity and mortality rates were similar. In patients aged >70 years, the morbidity, liver dysfunction-related morbidity, and mortality rates were significantly higher in patients with than without sarcopenia (P < 0.05 each). In contrast, surgical outcomes were similar in patients with high and low visceral fat amounts. CONCLUSIONS: Sarcopenia was a risk factor for postoperative complications after major hepatectomy, particularly in elderly patients.


Asunto(s)
Hepatectomía/efectos adversos , Grasa Intraabdominal/diagnóstico por imagen , Músculo Esquelético/diagnóstico por imagen , Sarcopenia/complicaciones , Sarcopenia/diagnóstico por imagen , Anciano , Femenino , Hepatectomía/mortalidad , Humanos , Región Lumbosacra/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Factores de Riesgo , Tomografía Computarizada por Rayos X
13.
Cancer Sci ; 106(9): 1153-62, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26132727

RESUMEN

It has become evident that P-cadherin, one of the classical cadherins, contributes to the malignant behavior of several types of cancer. In this study, we analyzed the expression of P-cadherin and its clinicopathological and prognostic values in intrahepatic cholangiocarcinoma (ICC) and pancreatic cancer. Furthermore, we investigated the functional role of P-cadherin in these cancer cells by knockdown and overexpression in vitro and by analyzing the correlation between the P-cadherin expression and its promoter methylation status. Thirty of 59 ICC cases (51%) and 36 of 73 pancreatic cancer cases (49%) stained positive for P-cadherin with mainly membranous distribution in tumor cells by immunohistochemistry. P-cadherin expression was significantly correlated with several clinicopathological factors, which reflect tumor behavior, and was identified as an independent adverse prognostic factor for disease-free survival in patients with ICC (relative risk [RR] 2.93, P = 0.04) and pancreatic cancer (RR 2.68, P = 0.005) via multivariate analyses. P-cadherin downregulation by siRNA suppressed migration and invasion, and P-cadherin overexpression induced the opposite effects in both ICC and pancreatic cancer cells, without any effects on cell proliferation. P-cadherin expression was related to its promoter methylation status in both cell lines and cancer tissues. In summary, P-cadherin overexpression may serve as a useful biomarker of invasive phenotype and poor prognosis; P-cadherin expression was found to be regulated by its promoter methylation. These results suggest that P-cadherin represents a novel therapeutic target for the treatment of ICC and pancreatic cancer.


Asunto(s)
Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/patología , Cadherinas/genética , Colangiocarcinoma/genética , Colangiocarcinoma/patología , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Anciano , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Proliferación Celular/genética , Supervivencia sin Enfermedad , Regulación hacia Abajo/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Masculino , Pronóstico , Regiones Promotoras Genéticas/genética
14.
Ann Surg Oncol ; 21(12): 3817-26, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24841354

RESUMEN

BACKGROUND: The purpose of this study was to determine the relationship between serum zinc (Zn) level and clinicopathological profiles in patients with hepatocellular carcinoma (HCC). Furthermore, we investigate the influence of serum Zn level on the long-term prognosis after hepatectomy. METHODS: A retrospective analysis was conducted of 310 patients who underwent initial hepatectomy for HCC. The correlation between serum Zn level and preoperative liver functional indicator, pathological features, including the degree of hepatic fibrosis, and perioperative outcome were evaluated. The patients were divided into two groups (serum Zn ≤ 65 mg/dL; n = 71 and Zn > 65 mg/dL; n = 239), and their long-term prognosis were compared. RESULTS: There were strong correlations between preoperative serum Zn level and serum albumin (r = 0.47, P < 0.0001), branched-chain amino acids (r = 0.28, P < 0.0001), and hyaluronic acid level (r = -0.33, P < 0.0001). The patients with low Zn group were characterized as hepatitis C virus (HCV) infection, impaired liver function, background hepatic fibrosis, and pathological vascular invasion. The disease-free and overall survivals in the low Zn group were significantly lower than those in the high Zn group, especially in subgroup with HCV-related liver disease (P = 0.041 and 0.0004, respectively). Multivariate analyses showed that serum Zn level was an independent prognostic factor for overall survival (hazard ratio 1.79, P = 0.038). CONCLUSIONS: Serum Zn level reflects liver function and is useful for predicting the hepatic fibrosis before surgery. The prognosis of patients with HCC was found to be associated with preoperative serum Zn level, especially in patients with HCV-related chronic liver disease.


Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/patología , Hepatectomía/efectos adversos , Cirrosis Hepática/diagnóstico , Neoplasias Hepáticas/patología , Complicaciones Posoperatorias/diagnóstico , Zinc/sangre , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/cirugía , Femenino , Estudios de Seguimiento , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/etiología , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/etiología , Cuidados Preoperatorios , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia
15.
Hepatol Res ; 44(9): 964-74, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24245496

RESUMEN

AIM: Hepatectomy is feasible for patients with hepatocellular carcinoma (HCC) with good hepatic function who meet the Milan criteria. Several studies have indicated that tumor markers of HCC, α-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP percentage and protein induced by vitamin K absence/antagonist-II were good predictors of malignant potential. It is important to identify highly malignant cases of HCC, and the aim of this study was to clarify the impact of triple positive tumor markers as the prognostic factors for early stage HCC within the Milan criteria. METHODS: This study investigated 199 patients who underwent hepatectomy for HCC within the Milan criteria between January 2001 and May 2009. Cumulative recurrence-free survival (RFS), overall survival (OS) and clinicopathological parameters were analyzed according to the number of positive tumor markers. RESULTS: In patients with triple positive tumor markers, 5-year RFS and OS was poor (17.1 and 61.4%, respectively). Multivariate analyses revealed independent risk factors for recurrence to be hepatitis C virus antibody positivity, non-initial treatment for HCC and triple positive tumor markers, and the independent risk factors for OS were high indocyanine green retention rate at 15 min value, maximum tumor size and triple positive tumor markers. Pathologically invasive growth, microvascular invasion and moderate to poor differentiation were significantly related to the number of the three tumor markers. CONCLUSION: Triple positive tumor markers for early stage HCC within the Milan criteria showed poor prognosis and malignant characteristics. These markers could be a useful predictor for the degree of malignant potential in early stage HCC.

16.
Int J Clin Oncol ; 19(4): 629-33, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23999903

RESUMEN

BACKGROUND: Patients with unresectable pancreatic and biliary cancers sometimes need decompression due to obstruction of the gastrointestinal tract and/or biliary tract. The aim of this study was to determine the prognostic factors associated with an indication for palliative bypass surgery in patients with unresectable pancreatic and biliary cancers. METHODS: Between April 2005 and September 2011, 37 patients with unresectable pancreatic and biliary cancers underwent palliative bypass surgery. Prognostic factors were searched for among clinical characteristics, operation-related factors, and tumor-related factors using a prospective database. RESULTS: The median survival time (MST) of these patients was 4.6 months, with a 6-month survival rate of 40.5 %. A multivariate Cox proportional hazards regression analysis revealed that mGPS >2 was the only independent prognostic factor for bypass surgery. Patients with an mGPS of 2 had an MST of 1.7 months, and they had a significantly worse prognosis than mGPS 0-1 patients with an MST of 6.3 months. CONCLUSIONS: The mGPS is useful for predicting survival after surgical decompression due to gastrointestinal obstruction in patients with unresectable pancreatic and biliary cancers. Patients with a poor mGPS may not be indicated for palliative bypass surgery.


Asunto(s)
Neoplasias del Sistema Biliar/cirugía , Desviación Biliopancreática , Cuidados Paliativos , Neoplasias Pancreáticas/cirugía , Anciano , Anciano de 80 o más Años , Neoplasias del Sistema Biliar/patología , Procedimientos Quirúrgicos del Sistema Biliar , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/patología , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Tasa de Supervivencia
17.
Gan To Kagaku Ryoho ; 41(12): 1506-8, 2014 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-25731234

RESUMEN

BACKGROUND: Prognosis of patients with hepatocellular carcinoma (HCC) with macrovascular invasion is extremely poor even after hepatic resection. Herein, the efficacy of short-term adjuvant hepatic arterial infusion chemotherapy (HAI) for HCC with macrovascular invasion has been studied. PATIENTS AND METHODS: From 1997 to 2013, 39 patients with HCC (BVp3, Vv3, or B3) undergoing hepatic resection were enrolled(group A: adjuvant HAI, n=21, group B: hepatectomy alone, n=18). RESULTS: Clinical and demographic characteristics were similar in the 2 groups. Five-year disease-free survival (DFS) rates were 31.0% and 6.2% in group A and group B, respectively (p=0.008). In multivariate analysis for DFS, adjuvant HAI was the only independent prognostic factor (hazard ratio: 0.44, p=0.04). In group A, the intrahepatic recurrence rate was significantly lower (33% vs 72%, p=0.01) compared to group B, but rates of extrahepatic recurrence were similar in the 2 groups (19% vs 22%). The rate of overall survival was marginally higher in group A compared to group B (51% vs 19%, respectively, p= 0.06). CONCLUSION: Short-term adjuvant HAI after hepatic resection may significantly improve DFS for HCC patients with macrovascular invasion.


Asunto(s)
Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Adulto , Anciano , Carcinoma Hepatocelular/irrigación sanguínea , Carcinoma Hepatocelular/cirugía , Quimioterapia Adyuvante , Femenino , Hepatectomía , Humanos , Infusiones Intraarteriales , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Invasividad Neoplásica
18.
Respir Investig ; 62(4): 617-622, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38718435

RESUMEN

BACKGROUND: Thoracoscopy is useful for diagnosing unexplained pleural effusions. A sufficient specimen volume is often difficult to obtain using forceps biopsies (FBs) but can be obtained with pleural cryobiopsies (CBs). This study aimed to assess the utility and safety of CB during thoracoscopy in the Japanese population. METHODS: Patients who underwent thoracoscopic CBs at the Japanese Red Cross Medical Center between January 2017 and August 2023 were included in the study. Data were retrospectively analyzed, including clinical data, thoracoscopic findings, specimen size, diagnostic yield, and complications. The number of collected specimens and the freezing time were left to the discretion of the attending physician. RESULTS: Twenty-six patients underwent thoracoscopic CB. Specimens obtained by CB were larger than those obtained by FB. Primary lung cancer was the most common cause of pleural effusion, followed by malignant pleural mesothelioma. CB contributed to the diagnosis in 24 of 26 cases (92.3%) and FB contributed to the diagnosis in 11 of 18 cases (61.1%). Severe fibrosis could be diagnosed in all 3 cases by CB, but not by FB. The common complications of CB included bleeding at the biopsy site and atelectasis, but no severe complications occurred. CONCLUSIONS: The utility and safety of thoracoscopic CB for diagnosing pleural effusions in Japan were verified. The diagnostic yield, specimen size, and safety profile of CB support the diagnostic utility of this method.


Asunto(s)
Neoplasias Pulmonares , Derrame Pleural , Toracoscopía , Humanos , Estudios Retrospectivos , Toracoscopía/métodos , Toracoscopía/efectos adversos , Masculino , Femenino , Anciano , Biopsia/métodos , Biopsia/efectos adversos , Japón , Persona de Mediana Edad , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Derrame Pleural/etiología , Derrame Pleural/patología , Anciano de 80 o más Años , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/patología , Mesotelioma Maligno/diagnóstico , Mesotelioma Maligno/patología , Adulto
19.
Magn Reson Med Sci ; 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38494701

RESUMEN

17O-labeled water is a T2-shortening contrast agent used in proton MRI and is a promising method for visualizing cerebrospinal fluid (CSF) dynamics because it provides long-term tracking of water molecules. However, various external factors reduce the accuracy of 17O-concentration measurements using conventional signal-intensity-based methods. In addition, T2 mapping, which is expected to provide a stable assessment, is generally limited to temporal-spatial resolution. We developed the T2-prepared based on T2 mapping used in cardiac imaging to adapt to long T2 values and tested whether it could accurately measure 17O-concentration in the CSF using a phantom. The results showed that 17O-concentration in a fluid mimicking CSF could be evaluated with an accuracy comparable to conventional T2-mapping (Carr-Purcell-Meiboom-Gill multi-echo spin-echo method). This method allows 17O-imaging with a high temporal resolution and stability in proton MRI. This imaging technique may be promising for visualizing CSF dynamics using 17O-labeled water.

20.
Ann Nucl Med ; 38(7): 553-562, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38656630

RESUMEN

OBJECTIVE: To investigate the incidence of adverse events (AEs) following single and multiple administrations of I-131 metaiodobenzylguanidine (MIBG) therapy for inoperable pheochromocytomas and paragangliomas (PPGLs). METHODS: A single-center retrospective study was conducted on patients with inoperable PPGLs who underwent I-131 MIBG therapy between January 2000 and December 2020. A total of 28 patients with available electronic medical records were included. The treatment consisted of a single intravenous administration of 150 mCi (5.55 GBq) of I-131 MIBG. We evaluated the first MIBG treatment and repeated MIBG treatments performed within 200 days of the previous treatment. AEs for each treatment were evaluated using CTCAE version 4.0, and the statistical analysis was conducted at a significance level of p < 0.05. Objective response based on RECIST 1.1 criteria and biochemical response based on urinary catecholamines were assessed. RESULTS: The study included a total of 63 administrations, consisting of 28 single administrations (SAs), including the first administration for all 28 cases, and 35 multiple administrations (MAs), which included the second or later administrations. Hematological AEs were evaluable for 23 SAs and 29 MAs. Grade 3 or higher leukopenia occurred in 9.8% of all administrations, and Grade 3 or higher lymphopenia in 23.5%; both were manageable through observation. There were no significant differences in clinical AE Grades 1-2 (p = 0.32), hematological AE Grades 1-2 (p = 0.22), or hematological AE Grades 3-4 (p = 0.12) between MAs and SAs. Statistical analysis for each type of AE revealed significant increases in leukopenia (p < 0.01) and lymphopenia (p = 0.04). No significant difference in anemia, thrombocytopenia, or neutropenia was observed between MAs and SAs. There was no significant increase in the incidence rate of Grade 3 or higher hematological AEs for any of the parameters. The objective response rate was 0% for SAs and 36% for MAs. Biochemical response rates were 18% for SAs and 67% for MAs. CONCLUSION: In I-131 MIBG therapy for PPGLs, multiple administrations significantly increased only Grade 1 or 2 lymphopenia and leukopenia compared to single administration.


Asunto(s)
3-Yodobencilguanidina , Neoplasias de las Glándulas Suprarrenales , Paraganglioma , Feocromocitoma , Humanos , 3-Yodobencilguanidina/efectos adversos , 3-Yodobencilguanidina/uso terapéutico , Feocromocitoma/radioterapia , Estudios Retrospectivos , Masculino , Femenino , Paraganglioma/radioterapia , Persona de Mediana Edad , Adulto , Neoplasias de las Glándulas Suprarrenales/radioterapia , Anciano , Resultado del Tratamiento , Adulto Joven
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