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1.
Radiology ; 311(2): e232369, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38805727

RESUMEN

The American College of Radiology Liver Imaging Reporting and Data System (LI-RADS) standardizes the imaging technique, reporting lexicon, disease categorization, and management for patients with or at risk for hepatocellular carcinoma (HCC). LI-RADS encompasses HCC surveillance with US; HCC diagnosis with CT, MRI, or contrast-enhanced US (CEUS); and treatment response assessment (TRA) with CT or MRI. LI-RADS was recently expanded to include CEUS TRA after nonradiation locoregional therapy or surgical resection. This report provides an overview of LI-RADS CEUS Nonradiation TRA v2024, including a lexicon of imaging findings, techniques, and imaging criteria for posttreatment tumor viability assessment. LI-RADS CEUS Nonradiation TRA v2024 takes into consideration differences in the CEUS appearance of viable tumor and posttreatment changes within and in close proximity to a treated lesion. Due to the high sensitivity of CEUS to vascular flow, posttreatment reactive changes commonly manifest as areas of abnormal perilesional enhancement without washout, especially in the first 3 months after treatment. To improve the accuracy of CEUS for nonradiation TRA, different diagnostic criteria are used to evaluate tumor viability within and outside of the treated lesion margin. Broader criteria for intralesional enhancement increase sensitivity for tumor viability detection. Stricter criteria for perilesional enhancement limit miscategorization of posttreatment reactive changes as viable tumor. Finally, the TRA algorithm reconciles intralesional and perilesional tumor viability assessment and assigns a single LI-RADS treatment response (LR-TR) category: LR-TR nonviable, LR-TR equivocal, or LR-TR viable.


Asunto(s)
Carcinoma Hepatocelular , Medios de Contraste , Neoplasias Hepáticas , Ultrasonografía , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/radioterapia , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/radioterapia , Ultrasonografía/métodos , Sistemas de Información Radiológica , Hígado/diagnóstico por imagen , Resultado del Tratamiento
2.
Hepatol Res ; 52(9): 754-761, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35635496

RESUMEN

AIM: The risk of hepatitis B virus (HBV) reactivation with immune checkpoint inhibitors (ICIs) is an important issue that has not yet been fully investigated. ICI is also expected to have an antiviral effect on HBV due to its immune tolerance inhibitory effect. We herein investigated the risk of HBV reactivation and the antiviral effect of ICI administration. METHODS: This study included 892 patients on ICIs between September 2014 and May 2021 at our hospital. The frequency of HBV reactivation and antiviral effects were investigated. RESULTS: Among the 892 patients who underwent ICI, 27 were hepatitis B surface antigen (HBsAg) positive. HBV reactivation was evaluated in 24 cases, among which 4.1% (1/24) had HBV reactivation. Nucleic acid analog prophylaxis was not administered to patients with reactivation. In a study of 15 cases, the amount of HBsAg decreased from baseline; 2.18 ± 0.77 log to 48 weeks later; 1.61 ± 1.38 log (p = 0.17). Forty-eight weeks after the start of ICI, disappearance of HBsAg was observed in two out of 15 cases (13.3%), and one case each with and without nucleic acid analog. CONCLUSION: In rare cases, HBsAg-positive patients may be reactivated by ICI administration. On the other hand, when ICI is administered, it is expected to have an antiviral effect on HBV due to its immune tolerance inhibitory effect, and future drug development is expected.

3.
Hepatol Res ; 52(10): 888-892, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35860944

RESUMEN

AIM: We report a rare case of immune-related cholangitis in which the natural course could be demonstrated. CASE PRESENTATION: Eight courses of pembrolizumab maintenance therapy were given as first-line treatment for squamous cell lung cancer; however, the patient was subsequently hospitalized due to a rapid increase in hepatobiliary enzymes. On endoscopic ultrasound, the common bile duct was dilated to 11 mm, and the wall, throughout its length from the papilla, was thickened. Endoscopic retrograde cholangiopancreatography showed no obvious stenosis in the lower bile duct; however, a parapapillary diverticulum was found, and papillary incision and bile duct plastic stent insertion were carried out. However, the liver disorder did not improve and overt jaundice appeared subsequently; therefore, an immune-related cholangitis was suspected, and prednisolone (PSL) 35 mg/day was introduced from day 59 of admission. Following PSL initiation, a decrease in serum bilirubin level was observed; however, significant decrease was not observed in alkaline phosphatase. Given the history of recurrent infectious cholangitis, magnetic resonance cholangiopancreatography was carried out on day 70 of admission. The intrahepatic bile duct showed stenosis and dilated findings, which was considered to be a factor for repeated infectious cholangitis. CONCLUSION: No previous case reports have described the changes and progression in bile duct images in immune-related adverse events. Therefore, this case is noteworthy for considering the progression of immune-related cholangitis.

4.
Hepatol Res ; 51(7): 767-774, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33900663

RESUMEN

AIM: Both entecavir (ETV) and tenofovir alafenamide fumarate (TAF) are widely used to treat chronic hepatitis B (CHB) in Japan. However, it remains unclear whether the efficacy of TAF in decreasing the hepatitis B surface antigen (HBsAg) level, and its safety, are superior to those of ETV. This study aimed to report the long-term effects and safety of 96-week ETV and TAF treatment in patients with CHB. METHODS: A prospective comparative observational study was undertaken on the following two groups: patients with CHB who received continuous ETV (n = 32) and patients with CHB who were switched from ETV to TAF upon request (n = 48). The HBsAg, urinary ß2-microglobulin (ß2MG)/creatinine (Cr), urinary N-acetyl-ß-D-glucosaminidase (NAG)/Cr, and serum alanine aminotransferase (ALT) levels, estimated glomerular filtration rate (eGFR), and bone mineral density (lumbar spine and femur) at 96 weeks were compared. RESULTS: The two groups did not significantly differ with respect to mean age, male / female patient ratio, or rate of hepatitis B e antigen-positive status. The mean changes in serum HBsAg level and eGFR at 96 weeks were not significantly different between the two groups. The ß2MG/Cr and NAG/Cr levels at 96 weeks were similar between the two groups. Additionally, the bone mineral density of the lumbar spine and femur as well as the serum ALT did not significantly differ. CONCLUSIONS: When compared with patients who received continuous ETV, those who were introduced to TAF after ETV showed similar effects in terms of the decrease in HBsAg level and safety.

5.
Dig Endosc ; 33(5): 829-839, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33020955

RESUMEN

BACKGROUND AND AIMS: Pancreatic neuroendocrine neoplasms (PanNENs), including Grade 1 (G1) or G2 tumors, can have a poor prognosis. This study investigated the value of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for predicting the prognosis of PanNENs. METHODS: This single-center, retrospective study included 47 consecutive patients who underwent CH-EUS and were diagnosed with PanNEN by surgical resection or EUS-guided fine needle aspiration between December 2011 and February 2016. Patients were divided into aggressive and non-aggressive groups according to the degree of clinical malignancy. CH-EUS was assessed regarding its capacity for diagnosing aggressive PanNEN, the correspondence between contrast patterns and pathological features, and its ability to predict the prognosis of PanNEN. RESULTS: There were 19 cases of aggressive PanNEN and 28 cases of non-aggressive PanNEN. The aggressive group included three G1, four G2, three G3 tumors, three mixed neuroendocrine non-neuroendocrine neoplasms, and six neuroendocrine carcinomas. CH-EUS was superior to contrast-enhanced computed tomography for the diagnosis of aggressive PanNEN (P < 0.001): hypo-enhancement on CH-EUS was an indicator of aggressive PanNEN, with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 94.7%, 100%, 100%, 96.6%, and 97.9%, respectively. Among G1/G2 PanNENs, cases with hypo-enhancement on CH-EUS had a poorer prognosis than those with hyper/iso-enhancement (P = 0.0009). Assessment of 36 resected specimens showed that hypo-enhancement on CH-EUS was associated with smaller and fewer vessels and greater degree of fibrosis. CONCLUSION: Contrast-enhanced harmonic endoscopic ultrasonography may be useful for predicting the prognosis of PanNENs.


Asunto(s)
Tumores Neuroendocrinos , Neoplasias Pancreáticas , Medios de Contraste , Endosonografía , Humanos , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/cirugía , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/cirugía , Pronóstico , Estudios Retrospectivos
6.
Chemistry ; 26(43): 9471-9474, 2020 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-32181527

RESUMEN

Facile synthesis of various benzonaphthofurans was achieved by intramolecular hydroarylation of 1,4-disilyl-2-aryloxy-1,3-enynes followed by cycloaddition with arynes or alkenes and finally desilylaromatization. The three-step transformation can be operated sequentially in one-pot, providing with a range of furanoacenes easily and highly effectively.

7.
J Org Chem ; 85(19): 12262-12269, 2020 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-32786640

RESUMEN

The mechanism for the synthesis of 2,3-bismethylenechromanes obtained by the reaction between silylethynyloxyarenes and allylic pivalates and catalyzed by a palladium complex has been investigated using computational methods rooted in density functional theory. The reaction is promoted by a C-H bond activation and the consequent bond cleavage of both substrates, followed by a novel annulation. The whole mechanism of this reaction is described together with the drawbacks that could block it. The main role played by the allyl rotation, inducing selectivity, together with the lability of the phosphine ligand and base (Cs2CO3) effects are unraveled. Finally, the nature of the substrates was managed, confirming that ortho-allylated silylethynyloxybenzenes lead to the same type of annulated products.

8.
Hepatol Res ; 50(1): 67-74, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31301213

RESUMEN

AIM: To retrospectively investigate the potential benefit of ultrasound-ultrasound (US-US) overlay fusion guidance for local controllability of radiofrequency ablation (RFA) in the treatment of hepatocellular carcinoma (HCC). METHODS: Patients (n = 101) with 121 HCCs (mean ± SD, 1.8 ± 0.7 cm) who underwent RFA guided by US-US overlay fusion were included in the retrospective study. By overlaying pre/postoperative US, the tumor image could be projected onto the ablative hyperechoic zone. The ablative margin could thereby be evaluated three-dimensionally during the RFA procedure. As a control group, all 325 patients with 453 HCCs who underwent conventional RFA during the same study period were selected. RESULTS: The total number of RF needle insertions per tumor for ablation was significantly more in the US overlay fusion group (mean 1.9 vs. 1.2; P < 0.01). The technical success rates of ablation after a single session were 100% (101/101) and 96.6% (314/325) for the US overlay fusion group and the control group, respectively. For early assessment of RFA response, 5-mm safety margins were achieved in 89.3% (108/121) and 47.0% (213/453) of nodules in the US overlay fusion group and the control group, respectively (P < 0.01). During the follow-up period (median 19 months), the 2-year local tumor progression rates were 0.8% (1/121) and 6.0% (27/453) in the US overlay fusion group and the control group, respectively (P = 0.022, log-rank test). CONCLUSIONS: US-US overlay fusion guidance can be highly effective for safety margin achievement in RFA for HCC, providing a lower risk of local tumor progression.

9.
Ultraschall Med ; 41(5): 562-585, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32707595

RESUMEN

The present, updated document describes the fourth iteration of recommendations for the hepatic use of contrast enhanced ultrasound (CEUS), first initiated in 2004 by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). The previous updated editions of the guidelines reflected changes in the available contrast agents and updated the guidelines not only for hepatic but also for non-hepatic applications.The 2012 guideline requires updating as previously the differences of the contrast agents were not precisely described and the differences in contrast phases as well as handling were not clearly indicated. In addition, more evidence has been published for all contrast agents. The update also reflects the most recent developments in contrast agents, including the United States Food and Drug Administration (FDA) approval as well as the extensive Asian experience, to produce a truly international perspective.These guidelines and recommendations provide general advice on the use of ultrasound contrast agents (UCA) and are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis to improve the management of patients.


Asunto(s)
Medios de Contraste , Ultrasonografía , Medios de Contraste/normas , Humanos , Ultrasonografía/normas
10.
J Med Ultrasound ; 28(2): 59-82, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32874864

RESUMEN

The first edition of the guidelines for the use of ultrasound contrast agents was published in 2004, dealing with liver applications. The second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some nonliver applications. The third edition of the contrast-enhanced ultrasound (CEUS) guidelines was the joint World Federation for Ultrasound in Medicine and Biology-European Federation of Societies for Ultrasound in Medicine and Biology (WFUMB-EFSUMB) venture in conjunction with other regional US societies such as Asian Federation of Societies for Ultrasound in Medicine and Biology, resulting in a simultaneous duplicate on liver CEUS in the official journals of both WFUMB and EFSUMB in 2013. However, no guidelines were described mainly for Sonazoid due to limited clinical experience only in Japan and Korea. The new proposed consensus statements and recommendations provide general advice on the use of Sonazoid and are intended to create standard protocols for the use and administration of Sonazoid in hepatic and pancreatobiliary applications in Asian patients and to improve patient management.

11.
J Med Virol ; 91(10): 1804-1810, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31199513

RESUMEN

Tenofovir alafenamide (TAF) is a newly developed prodrug of tenofovir (TFV). We divided 48 chronic hepatitis B patients who had taken entecavir (ETV) for ≥2 years into two groups: the ETV continuation (n = 24) and the TAF switching (n = 24) groups, and compared the antiviral effects and safety until 48 weeks after the start of the study. There were no significant differences in the alterations in the serum levels of HBs antigen (HBsAg) level between the ETV continuation and the TAF switching groups at 24 or 48 weeks. We also examined the effect of baseline HBsAg level on the decrease of HBsAg during the treatment; in the TAF switching group, the decrease of HBsAg level at 48 weeks was more significant in patients with low baseline HBsAg (<800 IU/mL) than those with high baseline HBsAg ( >800 IU/mL) (change of HBsAg; - 0.029 vs - 0.132 for high and low baseline HBsAg, respectively, P = .007). Also, the effect on renal function was found to be comparable between the TAF switch group and the ETV continuation group. In this study, switching from ETV to TAF may represent higher efficacy for a decrease of HBsAg than a continuation of ETV among the patients with low baseline HBsAg level.


Asunto(s)
Adenina/análogos & derivados , Antivirales/uso terapéutico , Guanina/análogos & derivados , Hepatitis B Crónica/tratamiento farmacológico , Adenina/sangre , Adenina/uso terapéutico , Adulto , Anciano , Alanina , Antivirales/sangre , Femenino , Guanina/sangre , Guanina/uso terapéutico , Antígenos de Superficie de la Hepatitis B/sangre , Humanos , Masculino , Persona de Mediana Edad , Tenofovir/análogos & derivados
12.
Chemistry ; 25(2): 391-399, 2019 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-30024650

RESUMEN

Organo(trialkyl)silanes have several advantages, including high stability, low toxicity, good solubility, easy handling, and ready availability compared with heteroatom-substituted silanes. However, methods for the cross-coupling of organo(trialkyl)silanes are limited, most probably because of their exceeding robustness. Thus, a practical method for the cross-coupling of organo(trialkyl)silanes has been a long-standing challenging research target. This article discusses how aryl(trialkyl)silanes can be used in cross-coupling reactions. A pioneering example is CuII catalytic conditions with the use of electron-accepting aryl- or heteroaryl(triethyl)silanes and aryl iodides. The reaction forms biaryls or teraryls. This design concept can be extended to Pd/CuII -catalyzed cross-coupling polymerization reactions between such silanes and aryl bromides or chlorides and to CuI -catalyzed alkylation using alkyl halides.

13.
Eur Radiol ; 29(9): 5045-5051, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30963271

RESUMEN

Percutaneous radiofrequency ablation (RFA), a generally accepted alternative therapy for patients with liver metastases, is a minimally invasive approach with a favorable safety profile and a lower rate of major complications. The use of RFA or combined RFA plus resection can produce total tumor clearance in patients with unresectable liver metastases. However, the relatively high rate of local tumor progression has prevented the widespread use of RFA. Furthermore, its efficacy is controversial because there have been no comparisons for its effect on overall survival compared with standard options such as systemic chemotherapy. Meanwhile, immunotherapy has become a major research focus for oncology based on the recent successes reported for immune checkpoint inhibitors for melanoma, non-small cell lung cancer, gastric cancer, and other cancers. Immune checkpoints negatively regulate T cell function, and inhibition prevents the blockade of the immune system by cancer cells to prevent their destruction. Unfortunately, only some patients (< 25%) respond to immuno-oncology drugs, whereas other patients acquire resistance. However, RFA can induce massive necrotic cell death which might activate immunity and the presentation of cryptic antigens to induce tumor-specific T cell response. Because RFA can induce the rapid release of large amounts of tumor antigens, it can potentially stimulate transient immune responses to much tumor antigens. Combination therapies have induced synergistic enhancement of anticancer immune response in preclinical studies, indicating great promise for the future of oncologic treatment.Key Points • Only some patients respond to immuno-oncology drugs. • RFA causes the release of large amounts of cellular debris, a source of tumor antigens that elicit immune responses against tumors. • Combination RFA for liver metastases and immune checkpoint inhibitor therapies might synergistically enhance antitumor immunity.


Asunto(s)
Factores Inmunológicos/uso terapéutico , Inmunoterapia/métodos , Neoplasias Hepáticas/terapia , Ablación por Radiofrecuencia/métodos , Terapia Combinada , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundario , Metástasis de la Neoplasia , Tomografía Computarizada por Rayos X
14.
Eur Radiol ; 28(5): 1986-1993, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29196855

RESUMEN

OBJECTIVES: To assess the clinical feasibility of US-US image overlay fusion with evaluation of the ablative margin in radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). METHODS: Fifty-three patients with 68 HCCs measuring 0.9-4.0 cm who underwent RFA guided by US-US overlay image fusion were included in this retrospective study. By an overlay of pre-/postoperative US, the tumor image could be projected onto the ablative hyperechoic zone. Therefore, the ablative margin three-dimensionally could be shown during the RFA procedure. US-US image overlay was compared to dynamic CT a few days after RFA for assessment of early treatment response. Accuracy of graded response was calculated, and the performance of US-US image overlay fusion was compared with that of CT using a Kappa agreement test. RESULTS: Technically effective ablation was achieved in a single session, and 59 HCCs (86.8 %) succeeded in obtaining a 5-mm margin on CT. The response with US-US image overlay correctly predicted early CT evaluation with an accuracy of 92.6 % (63/68) (k = 0.67; 95 % CI: 0.39-0.95). CONCLUSION: US-US image overlay fusion can be proposed as a feasible guidance in RFA with a safety margin and predicts early response of treatment assessment with high accuracy. KEY POINTS: • US-US image overlay fusion visualizes the ablative margin during RFA procedure. • Visualizing the margin during the procedure can prompt immediate complementary treatment. • US image fusion correlates with the results of early evaluation CT.


Asunto(s)
Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Ablación por Catéter/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Ultrasonografía Intervencional/métodos , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/patología , Estudios de Factibilidad , Femenino , Humanos , Hígado/diagnóstico por imagen , Hígado/patología , Hígado/cirugía , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
15.
Angew Chem Int Ed Engl ; 57(7): 1987-1990, 2018 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-29316098

RESUMEN

Whereas aryl(trialkyl)silanes are considered to be ideal organometallic reagents for cross-coupling reactions owing to their stability, low toxicity, solubility, and easy accessibility, they are generally inert under typical cross-coupling conditions. Disclosed herein is a palladium/copper catalytic system that enables the cross-coupling of trimethyl, triethyl, tert-butyldimethyl, and triisopropyl aryl silanes with aryl bromides. This process is applicable to the sequential C-H and C-Si bond arylation of thiophenes and the synthesis of poly(thiophene-fluorene)s.

16.
J Am Chem Soc ; 139(40): 14013-14016, 2017 10 11.
Artículo en Inglés | MEDLINE | ID: mdl-28933842

RESUMEN

Straightforward synthesis of benzosiloles was achieved by the invention of Pd/acid-catalyzed intramolecular anti-hydroarylation of aryloxyethynyl(aryl)silanes via ortho-C-H bond activation. The aryloxy group bound to the ethynyl carbon is the key factor for this transformation.

17.
Cancer Sci ; 108(10): 1996-2003, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28777492

RESUMEN

Most hepatocellular carcinomas (HCC) develop as a result of chronic liver inflammation. We have shown that the oncoprotein gankyrin is critical for inflammation-induced tumorigenesis in the colon. Although the in vitro function of gankyrin is well known, its role in vivo remains to be elucidated. We investigated the effect of gankyrin in the tumor microenvironment of mice with liver parenchymal cell-specific gankyrin ablation (Alb-Cre;gankyrinf/f ) and gankyrin deletion both in liver parenchymal and non-parenchymal cells (Mx1-Cre;gankyrinf/f ). Gankyrin upregulates vascular endothelial growth factor expression in tumor cells. Gankyrin binds to Src homology 2 domain-containing protein tyrosine phosphatase-1 (SHP-1), mainly expressed in liver non-parenchymal cells, resulting in phosphorylation and activation of signal transducer and activator of transcription 3 (STAT3). Gankyrin deficiency in non-parenchymal cells, but not in parenchymal cells, reduced STAT3 activity, interleukin (IL)-6 production, and cancer stem cell marker (Bmi1 and epithelial cell adhesion molecule [EpCAM]) expression, leading to attenuated tumorigenic potential. Chronic inflammation enhances gankyrin expression in the human liver. Gankyrin expression in the tumor microenvironment is negatively correlated with progression-free survival in patients undergoing sorafenib treatment for HCC. Thus, gankyrin appears to play a critical oncogenic function in tumor microenvironment and may be a potential target for developing therapeutic and preventive strategies against HCC.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Resistencia a Antineoplásicos , Neoplasias Hepáticas/metabolismo , Niacinamida/análogos & derivados , Compuestos de Fenilurea/administración & dosificación , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Factor de Transcripción STAT3/metabolismo , Animales , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Interleucina-6/metabolismo , Hígado/metabolismo , Hígado/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Masculino , Ratones , Niacinamida/administración & dosificación , Niacinamida/farmacología , Compuestos de Fenilurea/farmacología , Complejo de la Endopetidasa Proteasomal/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 6/metabolismo , Proteínas Proto-Oncogénicas/genética , Sorafenib , Análisis de Supervivencia , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/metabolismo
18.
Acc Chem Res ; 49(1): 67-77, 2016 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-26651014

RESUMEN

Organic synthesis based on straightforward transformations is essential for environmentally benign manufacturing for the invention of novel pharmaceuticals, agrochemicals, and organoelectronic materials in order to ultimately realize a sustainable society. Metal-catalyzed C-H bond-cleaving functionalization has become a promising method for achieving the above goal. For site-selective C-H bond cleavage, so-called directing groups, i.e., ligands attached to substrates, are employed. Commonly utilized directing groups are carbonyls, imines, carboxyls, amides, and pyridyls, which σ-donate electron pairs to metals. On the other hand, unsaturated substrates such as alkenes and alkynes, which participate largely as reactants in organic synthesis, are prepared readily by a wide variety of synthetic transformations and are also employed as reactants in organometallic chemistry. Moreover, such unsaturated groups form complexes with some metals by ligation of their p orbitals via donation and back-donation. However, the use of unsaturated bonds as directing groups has not been studied extensively. We have been involved in the development of methods for the cleavage of C-H bonds by means of transition-metal catalysts to achieve new carbon-carbon bond-forming reactions and incidentally came to focus on the alkynoxy group (-OC≡C-), which shows a ketene-like resonance structure. We expected the alkynoxy group to interact electrophilically with a low-valent transition-metal complex in order to cleave adjacent C-H bonds. In this Account, we summarize our recent achievements on C-H activation based on interactions of palladium with the alkynoxy group in alkynyl aryl ethers. The alkynoxy group plays two roles in the transformation: as a directing group for adjacent C-H bond activation and as an acceptor for the carbon and hydrogen fragments. A typical example is palladium-catalyzed ortho-C-H bond activation in alkynoxyarenes followed by sequential insertion/annulation with internal alkynes and the alkynoxy group to produce 2-methylidene-2H-1-benzopyrans. Mechanistic studies have shown that the presence of both oxygen and alkynyl moieties is essential for selective ortho-C-H bond activation and subsequent annulation. In addition to internal alkynes, norbornene, allenes, isocyanates, and ketenes produce the corresponding oxacycles. It is worthy of note that benzoxadinones formed by the reaction with isocyanates exhibit solid-state luminescence. In addition, 2-methylphenyl alkynyl ethers and 2-alkynoxybiaryls undergo intramolecular annulation at the benzylic γ-position and aryl δ-position via C-H bond activation to give benzofurans and dibenzopyrans, respectively. The disclosed methods allow us to construct useful π-conjugated systems in a straightforward manner.

19.
Oncology ; 92 Suppl 1: 3-9, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27974712

RESUMEN

INTRODUCTION: Recently, the treatment of chronic hepatitis C has markedly advanced. A phase III clinical study of combination therapy with sofosbuvir (SOF) and ledipasvir (LDV) was conducted in Japan, and the additive therapeutic effects were reported. In this study, we report the results of treatment in our hospital. METHODS: Of 147 patients with chronic type C liver disease who had consulted our hospital since September 2015 and received SOF/LDV therapy, in 91 subjects a sustained virological response of 12 weeks (SVR12) could be evaluated. RESULTS: In all 91 patients, end treatment response was achieved. Subsequently, recrudescence was noted in 1 before the completion of treatment (week 12); an SVR12 was achieved in 90 patients (99%). The following adverse reactions were observed in 3 patients (3.3%): bradycardia, paroxysmal atrial fibrillation, and heart failure with QT prolongation, which were associated with heart disease. CONCLUSION: A favorable SVR was achieved by SOF/LDV therapy even in elderly patients, those with liver cirrhosis, or those having undergone radical treatment of liver cancer. Furthermore, a high tolerance was demonstrated, but adverse reactions associated with the heart may appear in patients with heart disease as an underlying disease; strict management during treatment is necessary.


Asunto(s)
Antivirales/administración & dosificación , Bencimidazoles/administración & dosificación , Fluorenos/administración & dosificación , Hepatitis C Crónica/tratamiento farmacológico , Sofosbuvir/administración & dosificación , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Combinación de Medicamentos , Femenino , Hepatitis C Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
20.
Oncology ; 92 Suppl 1: 29-34, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27974714

RESUMEN

OBJECTIVE: To compare contrast tissue harmonic imaging (THI) with low mechanical index (MI) and conventional contrast harmonic imaging (CHI) with respect to lesion visibility of hepatocellular carcinoma (HCC). METHODS: One hundred and twenty-five patients (84 men and 41 women, age range 39-94 years, mean age 74 years) with 100 naïve HCCs and 30 lesions after radiofrequency ablation (RFA) for HCC were evaluated. One hundred and four patients had liver cirrhosis of Child-Pugh class A, and the remaining 21 had Child-Pugh class B cirrhosis. The lesion conspicuity and intratumoral echogenicity during the postvascular phase were compared using conventional CHI and contrast THI with low MI. RESULTS: The MI values ranged from 0.20 to 0.30 on conventional CHI and from 0.30 to 0.35 on contrast THI. Regarding HCC lesion conspicuity, contrast THI with low MI was clearer in 79 lesions (60.8%), equal in 34 lesions (26.2%), and less clear in 17 lesions (13.1%) when compared with conventional CHI. The lesion conspicuity with contrast THI was significantly better than that with conventional CHI (p < 0.01). All of the postablative lesions were well delineated in patients who received RFA. CONCLUSION: Low-MI contrast THI was superior to conventional CHI with respect to lesion visibility of HCCs and might offer good imaging for the guiding of RFA.


Asunto(s)
Carcinoma Hepatocelular/diagnóstico por imagen , Diagnóstico por Imagen de Elasticidad/métodos , Neoplasias Hepáticas/diagnóstico por imagen , Ultrasonografía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Medios de Contraste , Femenino , Humanos , Cirrosis Hepática/diagnóstico por imagen , Masculino , Persona de Mediana Edad
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