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1.
Breast Cancer Res Treat ; 203(2): 205-214, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37833452

RESUMEN

PURPOSE: This study aimed to quantitatively estimate the changes in breast volume associated with radiotherapy in patients undergoing breast-conserving surgery and whole-breast irradiation (WBI). METHODS: Pre-WBI simulation computed tomography (CT) scans and post-WBI follow-up chest CT scans from a total of 1,151 breast cancer patients were analyzed using a deep-learning-driven auto-segmentation approach. The CT-based asymmetry index (CTAI) was calculated by dividing the volume of the irradiated breast by the volume of the contralateral breast. Significant breast shrinkage was defined as a CTAI < 0.85. To quantify changes in CTAI over the follow-up period, the CTAI ratio was determined as the post-WBI CTAI divided by the pre-WBI CTAI. A multivariate logistic regression analysis was conducted to identify potential variables associated with post-WBI significant breast shrinkage. RESULTS: The median CTAI values for pre- and post-WBI CT scans were 0.973 (interquartile range: 0.887-1.069) and 0.866 (interquartile range: 0.773-0.967), respectively. The difference between them was statistically significant (p < 0.001). Following WBI, there was an increase in the rate of significant breast shrinkage from 16.3 to 44.8%. The CTAI ratio showed a negative association with the time interval (p < 0.001, Pearson r = - 0.310). In the multivariate logistic regression analysis, lower pre-WBI CTAI, younger age, and longer interval between CT scans were found to be significantly associated with a higher occurrence of post-WBI significant breast shrinkage. CONCLUSION: Breast volume decreases following WBI, and this decrease is correlated with an increased duration after WBI. These findings highlight the long-term consequences of WBI on breast asymmetry.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Mama/diagnóstico por imagen , Mastectomía Segmentaria , Tomografía Computarizada por Rayos X/métodos
2.
Endoscopy ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38718833

RESUMEN

BACKGROUND: Disposable digital single-operator cholangioscopy (D-SOC) and direct peroral cholangioscopy (D-POC) using an ultraslim endoscope are established POC modalities for the diagnosis and treatment of various biliary diseases. We compared the usefulness of D-SOC and D-POC for the diagnosis of intraductal superficial lesions of the bile duct (ISL-Bs). METHODS: 38 consecutive patients with suspected biliary diseases who underwent both D-SOC and D-POC were enrolled. The primary outcome was ISL-B detection rate, and the secondary outcomes were technical success of POC and POC-guided forceps biopsy sampling (POC-FB), procedure time, visualization quality, and tissue adequacy. RESULTS: D-SOC had a higher technical success rate than D-POC but the difference was not statistically significant (100% vs. 92.1%, P = 0.25). D-POC had a marginally higher ISL-B detection rate (34.2% vs. 28.9%, P = 0.68) and significantly higher visualization quality (P = 0.03). The mean (SD) procedure time was significantly shorter with D-SOC (11.00 [1.33] vs. 19.03 [2.95] minutes, P<0.001). The technical success rate of POC-FB and tissue adequacy did not differ between the two techniques (D-SOC vs. D-POC: 81.8% vs. 84.6%, P = 0.69 and 77.8% vs. 90.9%, P = 0.57, respectively). CONCLUSIONS: Both POC systems were safe and useful for the detection, characterization, and diagnosis of minute ISL-Bs. While D-SOC displayed a shorter procedure time and a tendency for higher technical success rate, D-POC provided superior visualization quality, allowing detailed observation of the surface structure and microvascular patterns.

3.
Prev Med ; 178: 107793, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38052332

RESUMEN

OBJECTIVE: Many municipal districts in Korea face population decline owing to overall population decreases and aging. We investigated the association between geographic rurality and likelihood of receiving diabetes management education and diabetic retinopathy and diabetes-related kidney disease screenings among adults with diabetes. METHODS: Patient data were obtained from the 2021 Korea Community Health Survey (27,391 individuals; aged ≥19 years and physician-diagnosed with diabetes mellitus). Geographic rurality was categorized based on population decline as follows: with, at risk of, or without population decline. The association between geographic rurality and likelihood of receiving diabetes management education and diabetic retinopathy and diabetes-related kidney disease screenings was examined using multilevel logistic regression analyses. RESULTS: Among 27,391 patients with diabetes, 31.1% received diabetes education; 40.0% and 46.4% were screened for diabetic retinopathy and diabetes-related kidney disease, respectively. Individuals residing in regions with population decline were less likely to receive diabetes education (odds ratio [OR] 0.62, 95% CI 0.50-0.75) and diabetic retinopathy (OR 0.79, 95% CI 0.70-0.90) and diabetes-related kidney disease (OR 0.64, 95% CI 0.55-0.75) screenings, as compared with their counterparts. CONCLUSIONS: Our findings highlight the importance of increased monitoring and providing diabetes education and screenings for patients with diabetes living in rural areas.


Asunto(s)
Diabetes Mellitus , Retinopatía Diabética , Enfermedades Renales , Animales , Adulto , Humanos , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/epidemiología , Escolaridad , Encuestas Epidemiológicas , República de Corea/epidemiología , Enfermedades Renales/complicaciones , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología
4.
Bioorg Chem ; 150: 107603, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38968905

RESUMEN

Inhibition of LSD1 was proposed as promising and attractive therapies for treating osteoporosis. Here, we synthesized a series of novel TCP-(MP)-Caffeic acid analogs as potential LSD1 inhibitors to assess their inhibitory effects on osteoclastogenesis by using TRAP-staining assay and try to explore the preliminary SAR. Among them, TCP-MP-CA (11a) demonstrated osteoclastic bone loss both in vitro and in vivo, showing a significant improvement in the in vivo effects compared to the LSD1 inhibitor GSK-LSD1. Additionally, we elucidated a mechanism that 11a and its precursor that 11e directly bind to LSD1/CoREST complex through FAD to inhibit LSD1 demethylation activity and influence its downstream IκB/NF-κB signaling pathway, and thus regulate osteoclastic bone loss. These findings suggested 11a or 11e as potential novel candidates for treating osteoclastic bone loss, and a concept for further development of TCP-(MP)-Caffeic acid analogs for therapeutic use in osteoporosis clinics.

5.
BMC Med Inform Decis Mak ; 24(1): 145, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38811961

RESUMEN

BACKGROUND: Nasal polyps and inverted papillomas often look similar. Clinically, it is difficult to distinguish the masses by endoscopic examination. Therefore, in this study, we aimed to develop a deep learning algorithm for computer-aided diagnosis of nasal endoscopic images, which may provide a more accurate clinical diagnosis before pathologic confirmation of the nasal masses. METHODS: By performing deep learning of nasal endoscope images, we evaluated our computer-aided diagnosis system's assessment ability for nasal polyps and inverted papilloma and the feasibility of their clinical application. We used curriculum learning pre-trained with patches of nasal endoscopic images and full-sized images. The proposed model's performance for classifying nasal polyps, inverted papilloma, and normal tissue was analyzed using five-fold cross-validation. RESULTS: The normal scores for our best-performing network were 0.9520 for recall, 0.7900 for precision, 0.8648 for F1-score, 0.97 for the area under the curve, and 0.8273 for accuracy. For nasal polyps, the best performance was 0.8162, 0.8496, 0.8409, 0.89, and 0.8273, respectively, for recall, precision, F1-score, area under the curve, and accuracy. Finally, for inverted papilloma, the best performance was obtained for recall, precision, F1-score, area under the curve, and accuracy values of 0.5172, 0.8125, 0.6122, 0.83, and 0.8273, respectively. CONCLUSION: Although there were some misclassifications, the results of gradient-weighted class activation mapping were generally consistent with the areas under the curve determined by otolaryngologists. These results suggest that the convolutional neural network is highly reliable in resolving lesion locations in nasal endoscopic images.


Asunto(s)
Aprendizaje Profundo , Endoscopía , Cavidad Nasal , Pólipos Nasales , Humanos , Cavidad Nasal/diagnóstico por imagen , Cavidad Nasal/patología , Pólipos Nasales/diagnóstico por imagen , Neoplasias Nasales/diagnóstico por imagen , Neoplasias Nasales/patología , Papiloma Invertido/diagnóstico por imagen , Papiloma Invertido/patología , Diagnóstico por Computador , Diagnóstico Diferencial , Masculino , Persona de Mediana Edad , Adulto
6.
J Biol Chem ; 298(5): 101816, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35278430

RESUMEN

Jumonji domain-containing protein-3 (JMJD3), a histone H3 lysine 27 (H3K27) demethylase, promotes endothelial regeneration, but its function in neointimal hyperplasia (NIH) of arteriovenous fistulas (AVFs) has not been explored. In this study, we examined the contribution of endothelial JMJD3 to NIH of AVFs and the mechanisms underlying JMJD3 expression during kidney failure. We found that endothelial JMJD3 expression was negatively associated with NIH of AVFs in patients with kidney failure. JMJD3 expression in endothelial cells (ECs) was also downregulated in the vasculature of chronic kidney disease (CKD) mice. In addition, specific knockout of endothelial JMJD3 delayed EC regeneration, enhanced endothelial mesenchymal transition, impaired endothelial barrier function as determined by increased Evans blue staining and inflammatory cell infiltration, and accelerated neointima formation in AVFs created by venous end to arterial side anastomosis in CKD mice. Mechanistically, JMJD3 expression was downregulated via binding of transforming growth factor beta 1-mediated Hes family transcription factor Hes1 to its gene promoter. Knockdown of JMJD3 enhanced H3K27 methylation, thereby inhibiting transcriptional activity at promoters of EC markers and reducing migration and proliferation of ECs. Furthermore, knockdown of endothelial JMJD3 decreased endothelial nitric oxide synthase expression and nitric oxide production, leading to the proliferation of vascular smooth muscle cells. In conclusion, we demonstrate that decreased expression of endothelial JMJD3 impairs EC regeneration and function and accelerates neointima formation in AVFs. We propose increasing the expression of endothelial JMJD3 could represent a new strategy for preventing endothelial dysfunction, attenuating NIH, and improving AVF patency in patients with kidney disease.


Asunto(s)
Fístula Arteriovenosa , Histona Demetilasas con Dominio de Jumonji/genética , Insuficiencia Renal Crónica , Animales , Fístula Arteriovenosa/genética , Fístula Arteriovenosa/patología , Regulación hacia Abajo , Células Endoteliales/metabolismo , Células Endoteliales/patología , Humanos , Hiperplasia/genética , Hiperplasia/patología , Histona Demetilasas con Dominio de Jumonji/metabolismo , Ratones , Neointima/genética
7.
Gastrointest Endosc ; 97(5): 898-910, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36642196

RESUMEN

BACKGROUND AND AIMS: Indirect diagnostic modalities are unsatisfactory for detecting intraductal neoplasm of the bile duct (IN-B), which can be detected by peroral cholangioscopy (POC) with narrow-band imaging (NBI). We investigated the POC findings of IN-B and developed a feasible endoscopic classification system. METHODS: Four hundred seventy-one patients who underwent direct POC from April 2008 to July 2020 were enrolled. Intraductal superficial lesions of the bile duct (ISL-Bs) were classified according to surface structure and microvascular pattern on POC with NBI and correlated to histologic findings after POC-guided forceps biopsy sampling (POC-FB) or surgery. The primary outcome was the detection rate of IN-Bs, and the secondary outcomes were the associations of POC findings with IN-B, technical success rates of POC and POC-FB, and adverse events. RESULTS: Direct POC was successful in 458 of 471 patients (97.2%). Among the patients, 131 (27.8%) exhibited ISL-Bs. The technical success rate of POC-FB was 94.7% (124/131). Among the 124 patients who underwent POC-FB, IN-B was revealed in 54 (43.5%), for a detection rate of 11.8% (54/458). Papillary lesions (P = .041), nodular lesions (P = .044), and irregularly or regularly dilated and tortuous vessels (P = .004 and P = .006, respectively) were POC findings associated with IN-B. The area under the receiver-operating characteristic curve of the novel classification system was .899. CONCLUSIONS: POC with NBI can be useful for the detection of IN-Bs. Our novel classification system based on both surface structure and microvascular pattern may allow differentiation of IN-B from ISL-Bs.


Asunto(s)
Neoplasias de los Conductos Biliares , Laparoscopía , Humanos , Endoscopía del Sistema Digestivo/métodos , Conductos Biliares/patología , Cateterismo , Neoplasias de los Conductos Biliares/patología
8.
Gastrointest Endosc ; 98(5): 848-856, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37473968

RESUMEN

BACKGROUND AND AIMS: EUS-guided hepaticogastrostomy (EUS-HPG) has a risk of serious procedural adverse events (AEs), but few dedicated devices for EUS-HPG are available. We evaluated the feasibility of a new partially covered self-expandable metal stent (PCSEMS) with an anchoring flange for EUS-HPG. METHODS: The feasibility of a stent featuring a proximal radiopaque uncovered portion 1.5 cm in length and a distal anchoring flange 20 mm in diameter was evaluated in consecutive patients undergoing EUS-HPG for unresectable malignant biliary obstruction. Primary outcomes were the technical and clinical success of EUS-HPG, and secondary outcomes were AEs, recurrent biliary obstruction (RBO), reintervention for RBO, and the technical feasibility of peroral cholangioscopy (POC) through the stent in situ. RESULTS: EUS-HPG was performed in 24 patients with unresectable malignant biliary obstruction. The technical and clinical success rates of EUS-HPG were 100% (24/24) and 91.7% (22/24), respectively. AEs developed after EUS-HPG in 8.3% of patients (2/24, cholangitis). RBO developed in 29.2% of patients (7/24), with a median cumulative time to RBO of 6.7 months. The causes of RBO were sludge formation (n = 4), hyperplasia at an uncovered portion (n = 2), and nonocclusive cholangitis (n = 1). Reintervention for RBO had a 100% success rate (7/7), and POC through the stent in situ was technically feasible in 7 of 8 patients with a stent diameter of 10 mm. CONCLUSIONS: EUS-HPG with a new PCSEMS can alleviate malignant biliary obstruction after failed ERCP. The novel stent evaluated in this study may prevent stent-related AEs, including stent migration, and allow advanced endoscopic interventions through the HPG route.

9.
Colorectal Dis ; 25(3): 431-442, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36281503

RESUMEN

AIM: The applicability of laparoscopic D3 oncological resection for splenic flexure cancer (SFC) surgery has not been fully explored due to technical difficulties and variations in surgical procedure. The aim of this work is to describe the feasibility of performing laparoscopic D3 resection in SFC and its impact on long-term survival. METHOD: A retrospective study on 47 out of 52 consecutive patients who underwent elective laparoscopic colectomy for SFC from December 2006 until December 2019 at Korea University Anam Hospital was performed. Data on patients' demographic and clinical features, surgical procedures, intraoperative and postoperative complications, pathological features and follow-up were collected. Categorical data are expressed as frequencies (n) and percentages (%). Continuous data are expressed as mean ± standard deviation and median (range). The Kaplan-Meier test was used to determine the overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS). RESULTS: The median age of patients was 67.0 years (range 27-87 years) and 72.3% were men. Ten (21.3%) patients presented with an obstructing tumour and underwent an elective laparoscopic colectomy, while 68.1% of patients presented with Stage II and III disease. The conversion rate was 4.3% and the morbidity rate was 31.9%. There was one postoperative death secondary to splenic infarction and anastomotic leak leading to multi-organ failure. Four deaths occurred due to disease progression during a median follow-up of 63.8 months. The rate of recurrence was 20%, the 5-year OS was 89.6% and the 5-year PFS was 72.9%. After R0 resection, the 5-year OS was 91.5% and the 5-year DFS was 74.5%. CONCLUSION: Laparoscopic D3 colectomy for SFC is feasible, with an acceptable morbidity and long-term oncological outcome when performed by highly skilled laparoscopic colorectal surgeons with knowledge of the complex anatomy around the splenic flexure. Further randomized trials should be performed to determine the advantage of laparoscopic D3 colectomy over conventional colectomy for SFC.


Asunto(s)
Colon Transverso , Neoplasias del Colon , Laparoscopía , Masculino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Colon Transverso/cirugía , Colon Transverso/patología , Neoplasias del Colon/patología , Estudios Retrospectivos , Resultado del Tratamiento , Laparoscopía/métodos , Colectomía/efectos adversos , Colectomía/métodos , Complicaciones Posoperatorias/cirugía
10.
Dig Dis Sci ; 68(1): 268-273, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35616805

RESUMEN

BACKGROUND AND AIMS: Endoscopic ultrasound (EUS) guided choledochoduodenostomy using a lumen-apposing metal stent (LAMS) allows access to the biliary system with a sufficiently large diameter stent. However, an appropriate endoscope for this purpose is required. We evaluated the feasibility of per-oral cholangioscopy (POC) using a multibending ultra-slim endoscope through a LAMS for EUS-guided choledochoduodenostomy. METHODS: Twelve patients who underwent EUS-guided choledochoduodenostomy, followed by POC via a LAMS, were enrolled. POC was performed with an multibending ultra-slim endoscope. The primary outcome was technical success, defined as examination of both hepatic ducts and either the distal common bile duct or stricture site within 10 min. The types of intervention and adverse events were also assessed. RESULTS: Technical success was achieved in all cases with the multibending ultra-slim endoscope. Narrow-band imaging endoscopy was performed in five cases (41.7%) and POC-guided targeted biopsy was performed in three cases (25.0%). Stone extraction during POC was performed in two patients (16.7%) and foreign body removal from the intrahepatic duct was performed in one patient. One patient underwent additional metal stent insertion under direct visualization. After POC, no stent migration or severe adverse events were seen in any case. CONCLUSIONS: POC using a multibending ultra-slim endoscope for diagnostic or therapeutic purposes can be performed effectively and safely through a LAMS after EUS-guided choledochoduodenostomy.


Asunto(s)
Coledocostomía , Endoscopía del Sistema Digestivo , Humanos , Coledocostomía/métodos , Estudios de Factibilidad , Endoscopía del Sistema Digestivo/métodos , Endoscopios , Conducto Colédoco , Stents/efectos adversos , Endosonografía , Drenaje , Resultado del Tratamiento
11.
Int J Mol Sci ; 24(4)2023 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-36835016

RESUMEN

Epigenetic regulators are involved in osteoclast differentiation. This study proposes that the inhibitors of epigenetic regulators could be effective in the treatment of osteoporosis. This study identified GSK2879552, a lysine-specific histone demethylase 1 (LSD1) inhibitor, as a candidate for the treatment of osteoporosis from epigenetic modulator inhibitors. We investigate the function of LSD1 during RANKL-induced osteoclast formation. LSD1 small-molecule inhibitors effectively inhibit the RANKL-induced osteoclast differentiation in a dose-dependent manner. LSD1 gene knockout in macrophage cell line Raw 264.7 also inhibits RANKL-mediated osteoclastogenesis. LSD1-inhibitor-treated primary macrophage cells and LSD1 gene knockout Raw 264.7 cells failed to show actin ring formation. LSD1 inhibitors prevent the expression of RANKL-induced osteoclast-specific genes. They also downregulated the protein expression of osteoclast-related markers in osteoclastogeneses, such as Cathepsin K, c-Src, and NFATc1. Although LSD1 inhibitors were shown to reduce the in vitro demethylation activity of LSD1, they did not modulate the methylation of Histone 3 K4 and K9 during osteoclastogenesis. The ovariectomy (OVX)-induced osteoporosis model revealed that GSK2879552 slightly restores OVX-induced cortical bone loss. LSD1 can be employed as a positive regulator to promote osteoclast formation. Hence, inhibition of LSD1 activities is a potential target for preventing bone diseases characterized by excessive osteoclast activities.


Asunto(s)
Resorción Ósea , Histona Demetilasas , Osteoclastos , Osteoporosis , Femenino , Resorción Ósea/metabolismo , Diferenciación Celular , Lisina/metabolismo , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteogénesis/efectos de los fármacos , Osteogénesis/genética , Osteoporosis/tratamiento farmacológico , Osteoporosis/metabolismo , Ovariectomía , Ligando RANK/metabolismo , Ratones , Histona Demetilasas/efectos de los fármacos , Histona Demetilasas/metabolismo , Animales
12.
Int J Mol Sci ; 24(5)2023 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-36901758

RESUMEN

Osteoporosis is a common skeletal disease; however, effective pharmacological treatments still need to be discovered. This study aimed to identify new drug candidates for the treatment of osteoporosis. Here, we investigated the effect of EPZ compounds, protein arginine methyltransferase 5 (PRMT5) inhibitors, on RANKL-induced osteoclast differentiation via molecular mechanisms by in vitro experiments. EPZ015866 attenuated RANKL-induced osteoclast differentiation, and its inhibitory effect was more significant than EPZ015666. EPZ015866 suppressed the F-actin ring formation and bone resorption during osteoclastogenesis. In addition, EPZ015866 significantly decreased the protein expression of Cathepsin K, NFATc1, and PU.1 compared with the EPZ015666 group. Both EPZ compounds inhibited the nuclear translocation of NF-κB by inhibiting the dimethylation of the p65 subunit, which eventually prevented osteoclast differentiation and bone resorption. Hence, EPZ015866 may be a potential drug candidate for the treatment of osteoporosis.


Asunto(s)
Resorción Ósea , Osteoporosis , Humanos , Resorción Ósea/metabolismo , FN-kappa B/metabolismo , Osteoclastos/metabolismo , Osteoporosis/metabolismo , Proteína-Arginina N-Metiltransferasas/metabolismo , Transducción de Señal , Ligando RANK
13.
Int J Mol Sci ; 24(3)2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36769036

RESUMEN

In this study, we designed and synthesized novel 1,4-dialkoxynaphthalene-2-alkyl imidazolium salt (IMS) derivatives containing both 1,4-dialkoxynaphthalene and imidazole, which are well known as pharmacophores. The cytotoxicities of these newly synthesized IMS derivatives were investigated in order to explore the possibility of using them to develop anticancer drugs. It was found that some of the new IMS derivatives showed good cytotoxic activities. In addition, an initial, qualitative structure-activity relationship is presented on the basis of observations of activity changes corresponding to structural changes.


Asunto(s)
Antineoplásicos , Neoplasias , Sales (Química)/farmacología , Sales (Química)/química , Línea Celular , Antineoplásicos/química , Relación Estructura-Actividad , Cloruro de Sodio , Estructura Molecular , Ensayos de Selección de Medicamentos Antitumorales , Línea Celular Tumoral
14.
Molecules ; 28(18)2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37764482

RESUMEN

Inflammatory-related diseases are becoming increasingly prevalent, leading to a growing focus on the development of anti-inflammatory agents, with a particular emphasis on creating novel structural compounds. In this study, we present a highly efficient synthetic method for direct N-arylation to produce a variety of N(2)-arylindazol-3(2H)-ones 3, which exhibit anti-inflammatory activity. The Chan-Evans-Lam (CEL) coupling of N(1)-benzyl-indazol-3-(2H)-ones 1 with arylboronic acids 2 in the presence of a copper complex provided the corresponding N(2)-arylindazol-3(2H)-ones 3 in good-to-excellent yields, as identified with NMR, MS, and X-ray crystallography techniques. The cell viability and anti-inflammatory effects of the synthesized compounds (3 and 5) were briefly assessed using the MTT method and Griess assay. Among them, compounds 5 exhibited significant anti-inflammatory effects with negligible cell toxicity.

15.
Plant Cell Environ ; 45(4): 1049-1064, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35098547

RESUMEN

Chemical pesticides are still frequently overused to diminish such crop loss caused by biotic stress despite the threat to humans and the environment. Thus, it is urgent to find safer and more effective defense strategies. In this study, we report that caffeine, implanted through a transgenic approach, enhances resistance against variable biotic stresses in rice without fitness cost. Caffeine-producing rice (CPR) was generated by introducing three N-methyltransferase genes involved in the biosynthesis of caffeine in coffee plants. The CPR plants have no differences in morphology and growth compared to their wild-type counterparts, but they show strongly enhanced resistance to both bacterial leaf blight, rice blast, and attack of white-backed planthoppers. Caffeine acts as a repellent agent against rice pathogens. Moreover, caffeine triggers a series of Ca2+ signalling-like processes to synthesize salicylic acid (SA), a hormone associated with plant resistance. In CPR, phosphodiesterase was inhibited by caffeine, cAMP and cGMP increased, intracellular Ca2+ increased, phenylalanine lyase (PAL) was activated by OsCPK1, and SA synthesis was activated. This finding is a novel strategy to improve resistance against the biotic stresses of crops with a special type of defense inducer.


Asunto(s)
Cafeína , Oryza , Cafeína/farmacología , Resistencia a la Enfermedad/genética , Regulación de la Expresión Génica de las Plantas , Enfermedades de las Plantas/microbiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Ácido Salicílico/farmacología , Estrés Fisiológico/genética
16.
BMC Cancer ; 22(1): 1179, 2022 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-36384573

RESUMEN

BACKGROUND: Postoperative radiotherapy (PORT) could be useful for pN1 breast cancer patients who have undergone breast-conserving surgery (BCS) or mastectomy. However, the value of regional nodal irradiation (RNI) for BCS patients, and the indications for post-mastectomy radiotherapy (PMRT) for pN1 breast cancer mastectomy patients, have recently been challenged due to the absence of relevant trials in the era of modern systemic therapy. "PORT de-escalation" should be assessed in patients with pN1 breast cancer. METHODS: The PORT-N1 trial is a multicenter, randomized, phase 3 clinical trial for patients with pN1 breast cancer that compares the outcomes of control [whole-breast irradiation (WBI) and RNI/PMRT] and experimental (WBI alone/no PMRT) groups. PORT-N1 aims to demonstrate non-inferiority of the experimental group by comparing 7-year disease-free survival rates with the control group. Female breast cancer patients with pT1-3 N1 status after BCS or mastectomy are eligible. Participants will be randomly assigned to the two groups in a 1:1 ratio. Randomization will be stratified by surgery type (BCS vs. mastectomy) and histologic subtype (triple-negative vs. non-triple-negative). In patients who receive mastectomy, dissection of ≥5 nodes is required when there is one positive node, and axillary lymph node dissection when there are two or three positive nodes. Patients receiving neoadjuvant chemotherapy are not eligible. RNI includes a "high-tangent" or wider irradiation field. This study will aim to recruit 1106 patients. DISCUSSION: The PORT-N1 trial aims to verify that PORT de-escalation after BCS or mastectomy is safe for pN1 breast cancer patients in terms of oncologic outcomes and capable of reducing toxicity rates. This trial will provide information crucial for designing PORT de-escalation strategies for patients with pN1 breast cancer. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT05440149) on June 30, 2022.


Asunto(s)
Neoplasias de la Mama , Mastectomía Segmentaria , Humanos , Femenino , Mastectomía Segmentaria/métodos , Mastectomía/métodos , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Estudios Prospectivos , Escisión del Ganglio Linfático , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase III como Asunto
17.
Gastrointest Endosc ; 96(3): 512-521, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35469893

RESUMEN

BACKGROUND AND AIMS: Direct peroral cholangioscopy (POC) can be useful when combined with narrow-band imaging (NBI) to explore the etiologies of indeterminate biliary strictures. We evaluated the efficacy of NBI compared with that of conventional white-light imaging (WLI) during POC diagnosis of indeterminate biliary strictures. METHODS: Consecutive patients with indeterminate biliary strictures were enrolled from 2016 to 2019. The primary outcome was diagnostic accuracy, and secondary outcomes were technical success, adverse events, and visualization quality when predicting malignancy. RESULTS: Seventy-one patients underwent direct POC under NBI during targeted biopsy sampling. The strictures were successfully explored and adequate biopsy samples obtained in 67 of 71 patients (94.4%). In terms of visual impression, WLI and NBI afforded 75.0% and 87.5% sensitivity, 82.9 and 91.4% specificity, and 82.8 and 91.3% accuracy, respectively. The areas under the WLI and NBI receiver-operating characteristic curves were .80 and .96 (P = .01). Under NBI, the visualization quality of surface structures, microvessels, and lesional margins was higher than that under conventional WLI (P < .05). CONCLUSIONS: Direct POC under NBI effectively and accurately predicts malignancies of indeterminate biliary strictures. NBI effectively illuminated surface structures, microvessels, and lesional margins.


Asunto(s)
Neoplasias de los Conductos Biliares , Colestasis , Neoplasias de los Conductos Biliares/complicaciones , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Biopsia/efectos adversos , Colestasis/complicaciones , Colestasis/etiología , Constricción Patológica/etiología , Humanos , Imagen de Banda Estrecha
18.
Endoscopy ; 54(4): 384-388, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34229357

RESUMEN

BACKGROUND: Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) using a lumen-apposing metal stent (LAMS) has rendered endoscopic gallbladder assessment through a stent possible, but an appropriate endoscope is required. We assessed the feasibility of peroral cholecystoscopy (POCC) using a multibending ultraslim endoscope passed through a LAMS after EUS-GBD. METHODS: 14 patients with a LAMS for EUS-GBD who consecutively underwent POCC were included. POCC was performed using a multibending endoscope inserted through the LAMS. The primary outcome was the technical success rate, defined as complete endoscopic examination of the gallbladder from the orifice of the cystic duct to the fundus. The types of intervention and adverse events were recorded. RESULTS: 17 POCCs were performed in 14 patients. Of the 17 POCCs, 15 (88.2 %) were technically successful. Narrow-band imaging endoscopy was performed in 12 procedures (70.6 %), and cholecystoscopy-guided target biopsies were obtained in six. Gallstone extraction was performed in two patients. After POCC, all LAMSs remained stable and no adverse events were observed. CONCLUSIONS: POCC using a multibending ultraslim endoscope can be effectively and safely performed through a LAMS after EUS-GBD.


Asunto(s)
Colecistitis Aguda , Colecistitis Aguda/etiología , Colecistitis Aguda/cirugía , Drenaje/métodos , Endoscopios , Endosonografía/métodos , Estudios de Factibilidad , Humanos , Stents , Resultado del Tratamiento , Ultrasonografía Intervencional
19.
Int J Colorectal Dis ; 37(9): 2085-2098, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36042031

RESUMEN

PURPOSE: Describe differences on recurrence patterns of mid-low rectal cancers treated with neoadjuvant chemoradiotherapy and low anterior resection between laparoscopic and robotic approach. METHODS: Patients were identified from a prospectively maintained institutional database between 2006 and 2019. Demographics, clinicopathological features, recurrence, and survival were investigated. Cox regression analysis was performed for risk factor analysis. RESULTS: A total of 160 patients (36 laparoscopic and 124 robotic) were included. Systemic recurrence rate was higher in laparoscopic group (27.8 vs 12.1%, p = 0.023). Liver recurrence was similar (11.1 vs 4.0%). Lung recurrence was higher after laparoscopy (19.4 vs 6.5%, p = 0.019). Time to lung recurrence was shorter after laparoscopy (13.0 months, IQR 4.0-20.0) compared to robotic (23.5 months, IQR 17.0-42.7) with no statistical significance. Time to liver recurrence was similar between laparoscopy (19.5 months, IQR 4.7-37.5) and robotic (19.0 months, IQR 10.5-33.0). Median overall survival after lung recurrence was different (p = 0.021) between laparoscopy (19.0 months, IQR 16.0-67.0) and robotic (74.0 months, IQR 50.2-112.2). OS after liver recurrence was similar between groups. Overall survival and lung disease-free survival were different between the two groups (p = 0.032 and p = 0.020), while liver disease-free survival and local recurrence-free survival were not. Laparoscopy (p = 0.030; HR 3.074, 95% CI: 1.112-8.496) was a risk factor for lung disease-free survival on multivariate analysis. CONCLUSION: Lung recurrences were less frequent and with better overall survival in the robotic group. Liver recurrences were not influenced by choice of approach. Trials are needed to investigate why the robotic approach affects distant metastasis control.


Asunto(s)
Laparoscopía , Neoplasias Pulmonares , Neoplasias del Recto , Procedimientos Quirúrgicos Robotizados , Quimioradioterapia , Humanos , Neoplasias Pulmonares/cirugía , Análisis Multivariante , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/cirugía , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Resultado del Tratamiento
20.
J Gastroenterol Hepatol ; 37(1): 225-232, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34750863

RESUMEN

BACKGROUND AND AIM: Durable biliary drainage is essential in patients with pancreatic cancer in the era of effective neoadjuvant chemotherapy (NACT). Plastic stent (PS) tends to occlude easily, and current metal stents are designed for nonresectable cancer. We evaluated the efficacy of a modified non-flared fully covered self-expandable metal stent (M-FCSEMS) during the perioperative period in patients with resectable or borderline resectable pancreatic cancer. METHODS: Consecutive patients with resectable or borderline resectable pancreatic ductal adenocarcinoma had a 12-mm M-FCSEMS (M-FCSEMS group) or 7-Fr PS (PS group) placed for biliary decompression before NACT or curative-intent surgery. The primary outcome was the re-intervention rate, and secondary outcomes were technical success, stent patency, and adverse events (AEs). RESULTS: Endoscopic stent placement was technically successful in all 60 patients. Twenty-three patients underwent surgery and 37 NACT before surgery. Re-intervention was performed in 10.0% (3/30) of patients in the M-FCSEMS group and 36.7% (11/30) of patients in the PS group (P = 0.030). The stent patency at 180 days was 89.8% (95% confidence interval, 77.3-100.0%) in the M-FCSEMS group and 30.2% (95% confidence interval, 11.4-80.0%) in the PS group (P < 0.0001). Stent-related AEs occurred in 10.0% (3/30) in the M-FCSEMS group and 40.0% (12/30) in the PS group (P = 0.015). Surgery-related AEs occurred in 10.5% (2/19) and 14.3% (3/21) in the M-FCSEMS and PS groups (P = 0.549). CONCLUSIONS: Modified non-flared fully covered self-expandable metal stents are effective and safe for durable biliary drainage in patients with resectable or borderline resectable pancreatic cancer during the perioperative period.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Cuidados Preoperatorios , Stents Metálicos Autoexpandibles , Carcinoma Ductal Pancreático/terapia , Drenaje , Humanos , Neoplasias Pancreáticas/terapia , Stents Metálicos Autoexpandibles/efectos adversos , Resultado del Tratamiento
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