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L-type amino acid transporter 1 (LAT1, SLC7A5) is an amino acid transporter expressed in various carcinomas, and it is postulated to play an important role in the proliferation of cancer cells through the uptake of essential amino acids. Cabazitaxel is a widely used anticancer drug for treating castration-resistant prostate cancer (CRPC); however, its effectiveness is lost when cancer cells acquire drug resistance. In this study, we investigated the expression of LAT1 and the effects of a LAT1-specific inhibitor, JPH203, in cabazitaxel-resistant prostate cancer cells. LAT1 was more highly expressed in the cabazitaxel-resistant strains than in the normal strains. Administration of JPH203 inhibited the growth, migration, and invasive ability of cabazitaxel-resistant strains in vitro. Phosphoproteomics using liquid chromatography-mass spectrometry to comprehensively investigate changes in phosphorylation due to JPH203 administration revealed that cell cycle-related pathways were affected by JPH203, and that JPH203 significantly reduced the kinase activity of cyclin-dependent kinases 1 and 2. Moreover, JPH203 inhibited the proliferation of cabazitaxel-resistant cells in vivo. Taken together, the present study results suggest that LAT1 might be a valuable therapeutic target in cabazitaxel-resistant prostate cancer.
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Benzoxazoles , Transportador de Aminoácidos Neutros Grandes 1 , Neoplasias de la Próstata , Taxoides , Tirosina/análogos & derivados , Masculino , Humanos , Fosforilación , Transportador de Aminoácidos Neutros Grandes 1/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Quinasas Ciclina-Dependientes/metabolismo , Línea Celular TumoralRESUMEN
BACKGROUND AND AIMS: We compared ERCP using a balloon-assisted endoscope (BE-ERCP) with EUS-guided antegrade treatment (EUS-AG) for removal of common bile duct (CBD) stones in patients with Roux-en-Y (R-Y) gastrectomy. METHODS: Consecutive patients who had previous R-Y gastrectomy undergoing BE-ERCP or EUS-AG for CBD stones in 16 centers were retrospectively analyzed. RESULTS: BE-ERCP and EUS-AG were performed in 588 and 59 patients, respectively. Baseline characteristics were similar, except for CBD diameter and angle. The technical success rate was 83.7% versus 83.1% (P = .956), complete stone removal rate was 78.1% versus 67.8% (P = .102), and early adverse event rate was 10.2% versus 18.6% (P = .076) in BE-ERCP and EUS-AG, respectively. The mean number of endoscopic sessions was smaller in BE-ERCP (1.5 ± .8 vs 1.9 ± 1.0 sessions, P = .01), whereas the median total treatment time was longer (90 vs 61.5 minutes, P = .001). Among patients with biliary access, the complete stone removal rate was significantly higher in BE-ERCP (93.3% vs 81.6%, P = .009). Negative predictive factors were CBD diameter ≥15 mm (odds ratio [OR], .41) and an angle of CBD <90 degrees (OR, .39) in BE-ERCP and a stone size ≥10 mm (OR, .07) and an angle of CBD <90 degrees (OR, .07) in EUS-AG. The 1-year recurrence rate was 8.3% in both groups. CONCLUSIONS: Effectiveness and safety of BE-ERCP and EUS-AG were comparable in CBD stone removal for patients after R-Y gastrectomy, but complete stone removal after technical success was superior in BE-ERCP.
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Colangiopancreatografia Retrógrada Endoscópica , Cálculos Biliares , Humanos , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Estudios Retrospectivos , Cálculos Biliares/diagnóstico por imagen , Cálculos Biliares/cirugía , Gastrectomía , Conducto Colédoco , Endoscopios , Resultado del TratamientoRESUMEN
PURPOSE OF REVIEW: We discussed the challenges associated with the clinical application of extracellular vesicles and summarized their potential impact on oncological clinical practice in urology. RECENT FINDINGS: Despite extensive research on extracellular vesicles, their clinical applications remain limited; this is likely to be because of small study cohorts, a lack of large-scale analyses, and the impact of variable extraction and storage methods on analysis outcomes. However, promising results have emerged from clinical trials targeting urinary extracellular vesicles in prostate cancer using ExoDx Prostate Test. The ExoDx Prostate Test has demonstrated its efficacy in diagnosing prostate cancer in previous studies and is the only FDA-approved kit for this purpose. Moreover, recent trials have investigated the use of the ExoDx Prostate Test to determine the optimal timing for biopsies in prostate cancer patients undergoing active surveillance. SUMMARY: We summarized recent studies on the potential of extracellular vesicles in the management of urological cancers. Particularly, the diagnosis of prostate cancer using the ExoDx Prostate Test has yielded positive results in several clinical trials. Additionally, while there are other studies suggesting its efficacy, most of these are based on retrospective analyses. These findings warrant further large-scale studies to optimize extracellular vesicle-based diagnostic and monitoring strategies. Although further research is required, extracellular vesicles would be attractive for early detection and surveillance.
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BACKGROUND: Thin delivery system stents can be inserted directly without the need for a tract dilation step and are expected to reduce bile leakage during endoscopic ultrasound-guided biliary drainage (EUS-BD). The present study retrospectively compared the safety and efficacy of EUS-BD using a thin metal stent (< 7.5 Fr) with those of EUS-BD using a conventional stent (≥ 7.5 Fr). METHODS: The present study enrolled 112 patients who underwent EUS-BD using metal stents for unresectable malignant biliary obstruction between April 2016 and July 2022. The primary endpoint was the rate of adverse events (AEs). The secondary endpoints were clinical success rate, procedure time, procedure success rate in the absence of the tract dilation step, recurrent biliary obstruction rate, time to biliary obstruction, and overall survival. Risk factors associated with early AEs were also evaluated. RESULTS: The rate of early AEs was significantly lower (12% vs. 35%, P = 0.013) and the procedure success without the tract dilation step was significantly higher (82% vs. 33%, P < 0.001) in the thin than in the conventional delivery system stent group. None of the other secondary endpoints differed significantly between the two groups. Multivariate analysis showed that employing the tract dilation step during EUS-BD was a significant independent risk factor for early AEs (skipping vs. employing; HR, 9.66; 95% CI, 1.13-83.0, P = 0.028). CONCLUSION: Employing the tract dilation step during EUS-BD was a significant risk factor for early AEs. Metal stents with a delivery diameter < 7.5 Fr can be inserted directly without the tract dilation step, resulting in lower early AE rates.
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Colangiopancreatografia Retrógrada Endoscópica , Colestasis , Humanos , Estudios Retrospectivos , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Dilatación/efectos adversos , Colestasis/etiología , Colestasis/cirugía , Endosonografía/métodos , Stents/efectos adversos , Drenaje/efectos adversos , Drenaje/métodos , Ultrasonografía Intervencional/efectos adversosRESUMEN
BACKGROUND: Few studies have compared endoscopic ultrasound (EUS)-guided hepaticogastrostomy (HGS) with EUS-guided antegrade metal stent placement (AGMS). The purpose of this study was to compare times to recurrent biliary obstruction (TRBO) in patients who underwent HGS using metal stents (MS) and those who underwent AGMS keeping access routes with plastic stents (AGMS-AR). METHODS: This study retrospectively evaluated consecutive patients who underwent HGS or AGMS between September 2016 and December 2022. TRBO, overall survival (OS), and adverse event (AE) rates were compared in the two groups. The risk factors for RBO were determined using a multivariable Cox proportional hazards model. RESULTS: This study included 32 patients in the HGS group and 30 in the AGMS-AR group. Technical success rate was significantly higher in the HGS than in the AGMS-AR group (100 vs. 80%; P = 0.009). The technical success rate without tract dilation was significantly higher in the AGMS-AR than in the HGS group (83 vs. 38%; P < 0.001). RBO rates were significantly higher in the HGS than in the AGMS-AR group (53 vs. 17%; P = 0.024), whereas AE rates did not differ significantly. TRBO differed significantly in the HGS and AGMS-AR groups (159 days vs. not reached, P = 0.011), whereas OS did not differ significantly. Multivariable analysis revealed that HGS was an independent risk factor for RBO (hazard ratio, 6.48, P = 0.014). CONCLUSION: TRBO was significantly longer in patients who underwent AGMS with PS than HGS. AGMS with PS may be effective after the failure of ERCP in patients with malignant biliary obstruction.
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OBJECTIVES: Detective flow imaging endoscopic ultrasonography (DFI-EUS) is a recent imaging modality developed for detecting fine vessels without the need for ultrasound contrast agents. The aim of the present study was to evaluate the utility of DFI-EUS for solid pancreatic lesions and to compare the diagnostic ability for pancreatic cancer (PC) between DFI-EUS, directional power Doppler (eFLOW) EUS, and contrast-enhanced harmonic (CH)-EUS. METHODS: Patients with a pancreatic lesion who underwent DFI-EUS, eFLOW-EUS, and CH-EUS between March 2019 and November 2023 were retrospectively enrolled. Final diagnoses were confirmed by pathologic examination of EUS-guided tissue acquisition and/or resected specimens. Lesions were categorized into the three patterns of poor, mild, and rich vascularity on DFI-EUS and eFLOW-EUS, and hypo-, iso-, and hypervascular on CH-EUS. PC was defined as a poor pattern on DFI-EUS and eFLOW-EUS, and a hypovascular pattern on CH-EUS. RESULTS: The final diagnoses of 90 examined tumors were PC (n = 57), inflammatory mass (n = 6), autoimmune pancreatitis (n = 13), neuroendocrine tumor (n = 9), and others (n = 5). The sensitivity, specificity, and accuracy for diagnosis of PC were 93%, 82%, and 88%, respectively, on DFI-EUS, 97%, 42%, and 77% on eFLOW-EUS, and 95%, 89%, and 92% on CH-EUS. The accuracy of DFI-EUS was significantly superior to eFLOW-EUS (P = 0.005), but no significant difference was found between DFI-EUS and CH-EUS. CONCLUSION: DFI-EUS is more sensitive for depicting vasculature than eFLOW-EUS, and has higher diagnostic sensitivity for PC. Evaluation of vascularity on DFI-EUS is useful for the differential diagnosis of pancreatic lesions without the need for intravenous contrast agent.
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OBJECTIVES: Contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) plays an important role in the diagnosis of pancreatic lesions. The aim of this study was to evaluate whether CH-EUS is useful for predicting the treatment efficacy of neoadjuvant chemotherapy (NAC) determined by pathological response. METHODS: Patients who underwent CH-EUS before chemotherapy and surgical resection were divided into two groups according to poor (group-P) or rich tumor vascularity (group-R) determined by enhancement pattern on early- and late-phase CH-EUS. The pathological response to chemotherapy was categorized according to Evans' classification. Pathological analysis showing tumor cell destruction (>50 %) defined a good response. RESULTS: Early-phase CH-EUS classified 44 patients into group-R and 50 into group-P, whereas late-phase CH-EUS classified 10 into group-R and 84 into group-P. Early-phase CH-EUS classification resulted in significantly higher numbers of patients with a good response in the rich group (n = 19) than in the poor group (n = 4; P = 0.0015). Multivariate analysis showed that assignment to the rich group was the strongest independent factor associated with chemosensitivity (P = 0.006, hazard ratio = 5.66, 95 % confidence interval: 1.17-19.27). In resectable patients, the enhancement pattern was the only independent factor associated with chemosensitivity (group-P vs. group-R, P = 0.003; HR [95 % CI], 14.59 [1.38-154.38]). Late-phase CH-EUS did not reveal a significant difference between group-P and group-R. CONCLUSIONS: Evaluation of vascular pattern on CH-EUS could be useful for predicting the efficacy of NAC in patients with pancreatic cancer. The enhancement pattern on CH-EUS could be a one of the useful features for determining NAC indications in resectable pancreatic cancer patients.
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Endosonografía , Neoplasias Pancreáticas , Humanos , Endosonografía/métodos , Terapia Neoadyuvante , Medios de Contraste , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Páncreas/diagnóstico por imagen , Páncreas/patologíaRESUMEN
Extracellular vesicles (EVs) are small particles with lipid bilayer membranes that are secreted by all cell types and are widely known as crucial intercellular communication mediators, shuttling biologically active molecules. The bone is a typically preferred site of cancer metastasis due to its unique cellular compositions and dynamics. Bone cell-derived EVs serve as regulators that orchestrate harmonious bone homeostasis. Cancer cells secrete specific EVs in a series of the bone metastatic process to dominate the bone microenvironment. Additionally, cancer cell-related EVs contribute to pre-metastatic niche formation, bone homeostasis disruption, and tumor bone progression and survival. Here, we investigated recent studies on EV-mediated crosstalk in the bone tumor microenvironment. Furthermore, this review aimed to elucidate the EV-based therapeutic perspectives for bone metastasis.
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Vesículas Extracelulares , Vesículas Extracelulares/metabolismo , Comunicación Celular/fisiología , Huesos , HomeostasisRESUMEN
Amino acid transporters are responsible for the uptake of amino acids, critical for cell proliferation. L-type amino acid transporters play a major role in the uptake of essential amino acids. L-type amino acid transporter 1 (LAT1) exerts its functional properties by forming a dimer with 4F2hc. Utilizing this cancer-specificity, research on diagnostic imaging and therapeutic agents for malignant tumors targeting LAT1 progresses in various fields. In hormone-sensitive prostate cancer, the up-regulation of L-type amino acid transporter 3 (LAT3) through the androgen receptor (AR) has been identified. On the other hand, in castration-resistant prostate cancer, the negative regulation of LAT1 through AR has been determined. Furthermore, 4F2hc: a binding partner of LAT1, was identified as the specific downstream target of Androgen Receptor Splice Variant 7: AR-V7. LAT1 has been suggested to contribute to acquiring castration resistance in prostate cancer, making LAT1 a completely different therapeutic target from anti-androgens and taxanes. Increased expression of LAT1 has also been found in renal and bladder cancers, suggesting a contribution to acquiring malignancy and progression. In Japan, clinical trials of LAT1 inhibitors for solid tumors are in progress, and clinical applications are now underway. This article will summarize the relationship between LAT1 and urological malignancies.
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Transportador de Aminoácidos Neutros Grandes 1 , Neoplasias de la Próstata , Neoplasias Urológicas , Humanos , Masculino , Sistemas de Transporte de Aminoácidos , Transportador de Aminoácidos Neutros Grandes 1/genética , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Receptores Androgénicos/genética , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/genéticaRESUMEN
Extracellular vesicles (EVs) are lipid membranous vesicles that are released from every type of cell. It has become clear that EVs are involved in a variety of biological phenomena, including cancer progression, and play critical roles in intracellular communication through the horizontal transfer of cellular cargoes such as proteins, DNA fragments, RNAs including mRNA and non-coding RNAs (microRNA, piRNA, and long non-coding RNA) and lipids. The most common cause of death associated with cancer is metastasis. Recent investigations have revealed that EVs are deeply associated with metastasis. Bone is a preferred site of metastasis, and bone metastasis is generally incurable and dramatically affects patient quality of life. Bone metastasis can cause devastating complications, including hypercalcemia, pathological fractures, spinal compression, and bone pain, which result in a poor prognosis. Although the mechanisms underlying bone metastasis have yet to be fully elucidated, increasing evidence suggests that EVs in the bone microenvironment significantly contribute to cancer progression and cancer bone tropism. Emerging evidence on EV functions in bone metastasis will facilitate the discovery of novel treatments. In this review, we will discuss the remarkable effects of EVs, especially on the tumor microenvironment in bone.
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Neoplasias Óseas/patología , Huesos/patología , Vesículas Extracelulares/patología , Metástasis de la Neoplasia/patología , Microambiente Tumoral/fisiología , Animales , Sistemas de Liberación de Medicamentos/métodos , HumanosRESUMEN
Stress-induced activation of p53 is an essential cellular response to prevent aberrant cell proliferation and cancer development. The ubiquitin ligase MDM2 promotes p53 degradation and limits the duration of p53 activation. It remains unclear, however, how p53 persistently escapes MDM2-mediated negative control for making appropriate cell fate decisions. Here we report that TBP-like protein (TLP), a member of the TBP family, is a new regulatory factor for the p53-MDM2 interplay and thus for p53 activation. We found that TLP acts to stabilize p53 protein to ensure long-lasting p53 activation, leading to potentiation of p53-induced apoptosis and senescence after genotoxic stress. Mechanistically, TLP interferes with MDM2 binding and ubiquitination of p53. Moreover, single cell imaging analysis shows that TLP depletion accelerates MDM2-mediated nuclear export of p53. We further show that a cervical cancer-derived TLP mutant has less p53 binding ability and lacks a proliferation-repressive function. Our findings uncover a role of TLP as a competitive MDM2 blocker, proposing a novel mechanism by which p53 escapes the p53-MDM2 negative feedback loop to modulate cell fate decisions.
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Mapas de Interacción de Proteínas , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Proteínas Similares a la Proteína de Unión a TATA-Box/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Apoptosis , Células HCT116 , Células HeLa , Humanos , Neoplasias/metabolismo , Neoplasias/patología , Estabilidad Proteica , Proteolisis , Proteínas Proto-Oncogénicas c-mdm2/análisis , Proteínas Similares a la Proteína de Unión a TATA-Box/análisis , Proteína p53 Supresora de Tumor/análisis , UbiquitinaciónRESUMEN
OBJECTIVES: To determine the predictors of testosterone recovery after termination of androgen deprivation therapy in high/intermediate-risk prostate cancer patients receiving external beam radiation therapy with neoadjuvant and adjuvant androgen deprivation therapy. METHODS: A total of 82 patients who underwent external beam radiation therapy with androgen deprivation therapy for prostate cancer were retrospectively analyzed. Serum testosterone levels after androgen deprivation therapy terminations were studied. Cox proportional hazard models and the Kaplan-Meier method were used for statistical analysis. RESULTS: Median age, baseline testosterone, nadir testosterone and duration of androgen deprivation therapy were 73 years, 456 ng/dL, 16 ng/dL and 26 months, respectively. Androgen deprivation therapy duration of 33 months (hazard ratio 0.13; P = 0.0018), nadir testosterone of 20 ng/dL (hazard ratio 0.35; P = 0.0112) and testosterone >50 ng/dL at 6 months after androgen deprivation therapy termination (hazard ratio 0.21; P = 0.0075) were significantly associated with testosterone recovery to normal levels (200 ng/dL) on multivariate analysis. Androgen deprivation therapy duration of 33 months (hazard ratio 0.31; P = 0.0023) and nadir testosterone of 20 ng/dL (hazard ratio 0.38; P = 0.0012) were significantly associated with testosterone recovery to the supracastrate level (50 ng/dL) on multivariate analysis. After dividing patients into three risk groups, the rate of testosterone recovery to the normal level after 2 years of androgen deprivation therapy termination was 100% in the low-risk group versus 20.8% in the high-risk group (P < 0.0001); the rate of testosterone recovery to the supracastrate level was 100% in the low-risk group versus 51.5% in the high-risk group (P < 0.0001). CONCLUSIONS: Duration of androgen deprivation therapy and achievement of nadir testosterone 20 ng/dL both predict testosterone recovery to the supracastrate level in prostate cancer patients undergoing external beam radiation therapy with androgen deprivation therapy.
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Antagonistas de Andrógenos/administración & dosificación , Neoplasias de la Próstata/terapia , Testosterona/sangre , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante/métodos , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Humanos , Estimación de Kaplan-Meier , Masculino , Terapia Neoadyuvante/métodos , Modelos de Riesgos Proporcionales , Próstata/efectos de los fármacos , Próstata/efectos de la radiación , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
Although the majority of gene expression is driven by TATA-binding protein (TBP)-based transcription machinery, it has been reported that TBP-related factors (TRFs) are also involved in the regulation of gene expression. TBP-like protein (TLP), which is one of the TRFs and exhibits the highest affinity to TFIIA among known proteins, has recently been showed to have significant roles in gene regulation. However, how the level of TLP is maintained in vivo has remained unknown. In this study, we explored the mechanism by which TLP protein is turned over in vivo and the factor that maintains the amount of TLP. We showed that TLP is rapidly degraded by the ubiquitin-proteasome system and that tight interaction with TFIIA results in protection of TLP from ubiquitin-proteasome-dependent degradation. The half-life of TLP was shown to be less than a few hours, and the proteasome inhibitor MG132 specifically suppressed TLP degradation. Moreover, knockdown and over-expression experiments showed that TFIIA is engaged in stabilization of TLPin vivo. Thus, we showed a novel characteristic of TLP, that is, interaction with TFIIA is essential to suppress proteasome-dependent turnover of TLP, providing a further insight into TLP-governed gene regulation.
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Complejo de la Endopetidasa Proteasomal/metabolismo , Proteínas Similares a la Proteína de Unión a TATA-Box/metabolismo , Factor de Transcripción TFIIA/metabolismo , Ubiquitina/metabolismo , Animales , Unión Competitiva , Regulación de la Expresión Génica , Células HCT116 , Células HeLa , Humanos , Ratones , Unión Proteica , Estabilidad Proteica , Proteolisis , Proteína de Unión a TATA-Box/metabolismoRESUMEN
TBP-TFIIA interaction is involved in the potentiation of TATA box-driven promoters. TFIIA activates transcription through stabilization of TATA box-bound TBP. The precursor of TFIIA is subjected to Taspase1-directed processing to generate α and ß subunits. Although this processing has been assumed to be required for the promoter activation function of TFIIA, little is known about how the processing is regulated. In this study, we found that TBP-like protein (TLP), which has the highest affinity to TFIIA among known proteins, affects Taspase1-driven processing of TFIIA. TLP interfered with TFIIA processing in vivo and in vitro, and direct binding of TLP to TFIIA was essential for inhibition of the processing. We also showed that TATA box promoters are specifically potentiated by processed TFIIA. Processed TFIIA, but not unprocessed TFIIA, associated with the TATA box. In a TLP-knocked-down condition, not only the amounts of TATA box-bound TFIIA but also those of chromatin-bound TBP were significantly increased, resulting in the stimulation of TATA box-mediated gene expression. Consequently, we suggest that TLP works as a negative regulator of the TFIIA processing and represses TFIIA-governed and TATA-dependent gene expression through preventing TFIIA maturation.
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Endopeptidasas/metabolismo , Proteínas Represoras/metabolismo , Proteínas Similares a la Proteína de Unión a TATA-Box/metabolismo , TATA Box , Factor de Transcripción TFIIA/metabolismo , Activación Transcripcional , Línea Celular , Cromatina/metabolismo , Células HeLa , Humanos , Proteína de Unión a TATA-Box/metabolismoRESUMEN
TBP-like protein (TLP) is one of the metazoan-restricted transcription factors participating in development and differentiation, though the molecular mechanism by which TLP regulates these processes remains unclear. In this study, we investigated the relationship between TLP and myogenesis of mouse C2C12 myoblasts. We found that TLP gene expression decreases during myogenic differentiation. Overexpression and knockdown of TLP revealed that the levels of muscle-specific myosin heavy chain and the myogenic transcription factor myogenin are downregulated by TLP. TLP inhibits the progression of morphological change from myoblasts to myotubes, thereby suppressing myogenesis. We further show that TLP represses the promoter activity of myogenin. The proximal AT-rich sequence of the myogenin promoter is responsible for TLP-mediated transcriptional repression. The results of this study suggest that TLP inhibits myogenesis through downregulation of the myogenin gene.
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Desarrollo de Músculos/genética , Desarrollo de Músculos/fisiología , Miogenina/genética , Regiones Promotoras Genéticas , Proteínas Similares a la Proteína de Unión a TATA-Box/genética , Proteínas Similares a la Proteína de Unión a TATA-Box/metabolismo , Animales , Diferenciación Celular , Línea Celular , Regulación hacia Abajo , Ratones , Fibras Musculares Esqueléticas/citología , Fibras Musculares Esqueléticas/metabolismo , Mioblastos Esqueléticos/citología , Mioblastos Esqueléticos/metabolismo , ARN Interferente Pequeño/genética , Proteínas Similares a la Proteína de Unión a TATA-Box/antagonistas & inhibidoresRESUMEN
BACKGROUND: One advantage of endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is that it is difficult for reflux cholangitis, caused by duodenal pressure increasing due to duodenal obstruction, to occur. In addition, since stent deployment is performed away from the malignant stricture site, longer stent patency than with endoscopic retrograde cholangiopancreatography (ERCP) may be obtained. However, no study has previously compared EUS-HGS and ERCP for patients without duodenal obstruction or surgically altered anatomy. The aim of the present study was to compare clinical outcomes between EUS-HGS and ERCP in normal anatomy patients without duodenal obstruction. METHOD: In the ERCP group, patients who initially underwent biliary drainage were included. In the EUS-HGS group, patients who underwent EUS-HGS due to failed biliary cannulation were included. Patients with an inaccessible papilla, such as with surgically altered anatomy or duodenal obstruction, were excluded. RESULTS: A total of 314 patients who underwent ERCP and EUS-HGS were enrolled in this study. Of the 314 patients, 289 underwent biliary stenting under ERCP guidance, and 25 patients underwent biliary stenting under EUS-HGS. After propensity score-matching analysis, the adverse event rate tended to be lower in the EUS-HGS group than in the ERCP group. Although overall survival was not significantly different between the EUS-HGS and ERCP groups (p = .228), stent patency was significantly longer in the EUS-HGS group (median 366.0 days) than in the ERCP group (median 76.5 days). CONCLUSIONS: EUS-HGS had a lower adverse event rate, shorter procedure time, and longer stent patency than ERCP in cases of normal anatomy without duodenal obstruction.
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TATA-binding protein-like protein (TLP) is involved in development, checkpoint, and apoptosis through potentiation of gene expression. TLP-overexpressing human cells, especially p53-containing cells, exhibited a decreased growth rate and increased proportion of G(1) phase cells. TLP stimulated expression of several growth-related genes including p21 (p21(Waf1/Cip1)). TLP-mediated activation of the p21 upstream promoter in cells was shown by a promoter-luciferase reporter assay. The p53-binding sequence located in the p21 upstream promoter and p53 itself are required for TLP-mediated transcriptional activation. TLP and p53 bound to each other and synergistically enhanced activity of the upstream promoter. TLP specifically activated transcription from the endogenous upstream promoter, and p53 was required for this activation. Etoposide treatment also resulted in activation of the upstream promoter as well as nuclear accumulation of TLP and p53. Moreover, the upstream promoter was associated with endogenous p53 and TLP, and the p53 recruitment was enhanced by TLP. The results of the present study suggest that TLP mediates p53-governed transcriptional activation of the p21 upstream promoter.
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Inhibidor p21 de las Quinasas Dependientes de la Ciclina/biosíntesis , Elementos de Respuesta/fisiología , Proteínas Similares a la Proteína de Unión a TATA-Box/metabolismo , Transcripción Genética/fisiología , Activación Transcripcional/fisiología , Proteína p53 Supresora de Tumor/metabolismo , Animales , Antineoplásicos Fitogénicos/farmacología , Células COS , Chlorocebus aethiops , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Etopósido/farmacología , Fase G1/efectos de los fármacos , Fase G1/fisiología , Células HeLa , Células Hep G2 , Humanos , Proteínas Similares a la Proteína de Unión a TATA-Box/genética , Transcripción Genética/efectos de los fármacos , Activación Transcripcional/efectos de los fármacos , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Detective flow imaging endoscopic ultrasonography (DFI-EUS) is an innovative imaging modality that was developed to detect fine vessels and low-velocity blood flow without contrast agents. We evaluate its utility for the differential diagnosis of gallbladder lesions and intraductal papillary mucinous neoplasms (IPMNs). We enrolled patients who underwent DFI-EUS, e-FLOW EUS, and contrast-enhanced EUS for gallbladder lesions or IPMNs. The detection of vessels using DFI-EUS and e-FLOW EUS was compared with that via contrast-enhanced EUS and pathological findings. The vessel pattern was also categorized as regular or irregular. Of the 33 lesions included, there were final diagnoses of 13 IPMNs and 20 gallbladder lesions. DFI-EUS was significantly superior to e-FLOW EUS for discriminating between mural nodules and mucous clots and between solid gallbladder lesions and sludge using the presence or absence of vessel detection in lesions (p = 0.005). An irregular vessel pattern with DFI-EUS was a significant predictor of malignant gallbladder lesions (p = 0.002). DFI-EUS is more sensitive than e-FLOW-EUS for vessel detection and the differential diagnosis of gallbladder lesions and IPMNs. Vessel evaluation using DFI-EUS may be a useful and simple method for differentiating between mural nodules and mucous clots in IPMN, between solid gallbladder lesions and sludge, and between malignant and benign gallbladder lesions.
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Characteristic distributions of Al, Mn, Fe, Ni, Zn, and Pb were investigated in the surface sediments of a small river (Niitsu River) flowing through both urban and agricultural areas, along with comparison with those from the upper main stream (Nodai River). The mean compositions of the most mobile metals were ordered as Zn = Mn > Ni = Pb = Fe > Al in the Niitsu River. They were Mn = Zn = Pb = Fe > Ni = Al in the Nodai River. Mn, Fe, Ni, and Zn in the Niitsu River showed higher compositions of mobile (2.9%-36%) and oxidizable (6.6%-16%) phases than those in the Nodai River. The Ni and Zn in the Niitsu River also had higher reducible phase composition (15% and 16%, respectively). In the Niitsu River, Pb had the higher oxidizable composition (29%). Over 90% of Al was in the lithogenic phase in the two rivers.
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Agricultura/estadística & datos numéricos , Sedimentos Geológicos/química , Metales/análisis , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente , Japón , Ríos/química , Contaminación Química del Agua/estadística & datos numéricosRESUMEN
The characteristic distributions of 12 metals (Al, Ti, Cr, Mn, Fe, Co, Ni, Cu, Zn, Sr, Cd and Pb) were investigated in surface sediments from a small river (Niitsu River) flowing through both urban and agricultural areas by comparison with those from the upper main stream (Nodai River). Among the investigated metals, the mean concentrations of Al, Cr, Fe, Zn, Cd and Pb in the Niitsu River were significantly higher than those in the Nodai River. The investigated sites can be characterized by the principal components 1-3.