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1.
Glycobiology ; 2020 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-32601684

RESUMO

Loss-of-function variants in CHST14 cause a dermatan 4-O-sulfotransferase deficiency named musculocontractural Ehlers-Danlos syndrome-CHST14 (mcEDS-CHST14), resulting in complete depletion of the dermatan sulfate moiety of decorin glycosaminoglycan (GAG) chains, which is replaced by chondroitin sulfate. Recently, we uncovered structural alteration of GAG chains in the skin of patients with mcEDS-CHST14. Here, we conducted the first systematic investigation of Chst14 gene-deleted homozygote (Chst14-/-) mice. We used skin samples of wild-type (Chst14+/+) and Chst14-/- mice. Mechanical fragility of the skin was measured with a tensile test. Pathology was observed using light microscopy, decorin immunohistochemistry, and electron microscopy (EM) including cupromeronic blue (CB) staining. Quantification of chondroitin sulfate and dermatan sulfate was performed using enzymatic digestion followed by anion-exchange HPLC. In Chst14-/- mice, skin tensile strength was significantly decreased compared with that in Chst14+/+ mice. EM showed that collagen fibrils were oriented in various directions to form disorganized collagen fibers in the reticular layer. Through EM-based CB staining, rod-shaped linear GAG chains were found to be attached at one end to collagen fibrils and protruded outside of the fibrils, in contrast to them being round and wrapping the collagen fibrils in Chst14+/+ mice. A very low level of dermatan sulfate disaccharides was detected in the skin of Chst14-/- mice by anion-exchange chromatography. Chst14-/- mice, exhibiting similar abnormalities in the GAG structure of decorin and collagen networks in the skin, could be a reasonable model for skin fragility of patients with mcEDS-CHST14, shedding light on the role of dermatan sulfate in maintaining skin strength.

2.
JCI Insight ; 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32603314

RESUMO

Macrolide antibiotics exert anti-inflammatory effects; however, little is known regarding their immunomodulatory mechanisms. In this study, using two distinct mouse models of mucosal inflammatory disease (LPS-induced acute lung injury and ligature-induced periodontitis), we demonstrated that the anti-inflammatory action of erythromycin (ERM) is mediated through upregulation of the secreted homeostatic protein DEL-1. Consistent with the anti-neutrophil recruitment action of endothelial cell-derived DEL-1, ERM inhibited neutrophil infiltration in the lungs and the periodontium in a DEL-1-dependent manner. Whereas ERM (but not other antibiotics such as josamycin and penicillin) protected against lethal pulmonary inflammation and inflammatory periodontal bone loss, these protective effects of ERM were abolished in Del1-deficient mice. By interacting with the growth hormone secretagogue receptor (GHSR) and activating JAK2 in human lung microvascular endothelial cells, ERM induced C/EBPß-dependent DEL-1 transcription, which was mediated by MAPK p38. Moreover, ERM reversed IL-17-induced inhibition of DEL-1 transcription, in a manner that was not only dependent on JAK2 but also on PI3K/AKT signaling. As DEL-1 levels are severely reduced in inflammatory conditions and with aging, the ability of ERM to upregulate DEL-1 may be a novel approach for the treatment of inflammatory and aging-related diseases.

3.
J Oral Biosci ; 2020 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-32544616

RESUMO

BACKGROUND: The oral cavity serves as an entrance to the body and is therefore exposed to various exogenous stimuli, including mechanical forces, chemical agents, and bacterial components. The oral mucosa responds to these stimuli to maintain homeostasis and good oral health. The transient receptor potential vanilloid 1 (TRPV1) ion channel functions as an environment-sensing protein and is involved in a wide variety of cellular responses. Recent studies have revealed that epithelial TRPV1 ion channels in the oral cavity play pivotal roles in several pathophysiological conditions. In this review, we summarize the features of epithelial TRPV1 channels in the oral cavity and focus on their cellular function and pathogenicity with reference to related findings in other organs and tissues. HIGHLIGH: t: TRPV1 channels are widely expressed in epithelial cells in the oral cavity and play pivotal roles in fundamental cellular processes and disease progression. CONCLUSION: This review suggests that oral epithelial TRPV1 contributes to several cellular functions such as cell proliferation, barrier function, and inflammation. Further understanding of the characteristics of epithelial TRPV1 in the oral cavity may provide new insights into the prevention or treatment of diseases.

4.
Ann Rehabil Med ; 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32475095

RESUMO

Objective: To examine the efficacy and safety of an innovative, device-driven abdominal trunk muscle strengthening program, with the ability to measure muscle strength, to treat chronic low back pain (LBP) in elderly participants. Methods: Seven women with non-specific chronic LBP, lasting at least 3 months, were enrolled and treated with the prescribed exercise regimen. Patients participated in a 12-week device-driven exercise program which included abdominal trunk muscle strengthening and 4 types of stretches for the trunk and lower extremities. Primary outcomes were adverse events associated with the exercise program, improvement in abdominal trunk muscle strength, as measured by the device, and improvement in the numerical rating scale (NRS) scores of LBP with the exercise. Secondary outcomes were improvement in the Roland-Morris Disability Questionnaire (RDQ) score and the results of the locomotive syndrome risk test, including the stand-up and two-step tests. Results: There were no reports of increased back pain or new-onset abdominal pain or discomfort during or after the device-driven exercise program. The mean abdominal trunk muscle strength, NRS, RDQ scores, and the stand-up and two-step test scores were significantly improved at the end of the trial compared to baseline. Conclusion: No participants experienced adverse events during the 12-week strengthening program, which involved the use of our device and stretching, indicating the program was safe. Further, the program significantly improved various measures of LBP and physical function in elderly participants.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32596728

RESUMO

BACKGROUND: Chronic hypoxia may play a pivotal role in the development of diabetic nephropathy (DN). However, the precise mechanisms underlying progressive hypoxia-induced glomerular injury remain unclear. METHODS: We housed db/db mice in a hypoxia chamber (12% O2) for up to 16 weeks beginning at 8 weeks of age. Various urine, serum and kidney abnormalities and glomerular messenger RNA (mRNA) expression were compared with those in age-matched db/db mice housed under normoxia. RESULTS: Levels of urinary albumin and podocalyxin (PCX) were significantly higher in hypoxic mice early during hypoxia. Ultracentrifugation of urine samples revealed that podocytes in the hypoxic mice shed PCX-positive microparticles into the urine. After 16 weeks of hypoxia, the mice also had higher hematocrits with lower serum glucose and various degrees of mesangiolytic glomerulosclerosis with microaneurysms and the infrequent occurrence of nodular lesions. Immunohistologically, hypoxic mice showed significantly decreased endothelial cell densities early during hypoxia and decreased podocyte densities later. In both hypoxic and normoxic mice, glomerular macrophage and transforming growth factor-ß1 (TGF-ß1) staining significantly increased with aging, without changes in vascular endothelial growth factor or endothelial nitric oxide synthase (eNOS). Glomerular mRNA expression of monocyte chemoattractant protein-1, eNOS and TGF-ß1 was significantly enhanced in the hypoxic mice. CONCLUSIONS: These results indicate that chronic hypoxia induces advanced glomerulosclerosis with accelerated albuminuria triggered by mesangiolysis and podocyte injury in a murine model of DN.

6.
Eur Radiol ; 2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-32518984

RESUMO

OBJECTIVES: To evaluate the relationship between imperceptible T1 enhancement of papillary renal cell carcinoma (pRCC) on MR and intratumoral hemosiderin deposition. METHODS: One hundred ten pRCCs (≤ 7 cm) were evaluated by MR with in- and opposed-phase spoiled gradient echo (GRE) and T1-weighted spoiled GRE with fat suppression before and after contrast. Hemosiderin deposition was assessed by SIindex and Dindex on in- and opposed-phase images. SIindex and Dindex are calculated as (SIin - SIopp)/(SIin) × 100, where SIin and SIopp are tumor signal intensities on in- and opposed-phase images and (Din)/(Dopp), where Din and Dopp are tumor diameters on in- and opposed-phase images, respectively. The degree of tumor enhancement was classified as grade 1 (no), grade 2 (subtle), or grade 3 (definite). Tumor enhancement on CT was assessed when available. RESULTS: Five (5%), 10 (9%), and 95 (86%) tumors were categorized as grades 1, 2, and 3 enhancement, respectively. The mean SIindex was - 33.9, - 25.3, and 1.00, whereas the mean Dindex was 1.26, 1.05, and 1.00 in tumors with grades 1, 2, and 3 enhancement, respectively. Tumors with grade 1 enhancement had significantly lower SIindex (p = 0.001) and higher Dindex (p = 0.005) than those with grade 3 enhancement. Among six tumors with grade 1 or 2 enhancement and available CT, four tumors showed > 20 HU enhancement. CONCLUSIONS: pRCC with no subjective enhancement on contrast-enhanced MR showed hemosiderin deposition evident by lower SIindex and higher Dindex. Hemosiderin deposition might mask the tumor enhancement on MR. KEY POINTS: • 5% of papillary renal cell carcinoma showed imperceptible enhancement on contrast-enhanced MR. • Hemosiderin deposition in papillary renal cell carcinoma might mask the tumor enhancement on contrast-enhanced MR due to T2/T2*-shortening effects. • A renal lesion with extensive hemosiderin deposition but no perceptible enhancement on MR should be considered suspicious for papillary renal cell carcinoma.

7.
J Med Invest ; 67(1.2): 102-112, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32378592

RESUMO

Fibrocytes, which are bone marrow-derived collagen-producing cells, were reported to play a role in the pathogenesis of pulmonary fibrosis. However, their function in pulmonary fibrosis is unclear. We analyzed their function compared with that of monocytes and localization in fibrotic tissues in patients with idiopathic pulmonary fibrosis (IPF). We compared the gene expression profile of monocyte-derived fibrocytes with that of monocytes by microarray analysis. Proliferation and differentiation into myofibroblasts were examined by 3H-thymidine incorporation assay and Western blotting. We measured the level of growth factors in the culture supernatant of fibrocytes by ELISA. The localization of fibrocytes in lung tissues of patients with IPF was determined by immunofluorescence staining. Compared with monocytes, fibrocytes had higher expression of extracellular matrix- and growth factor-encoding genes, including PDGF-B, FGF-2 and VEGF-B. Although fibrocytes did not proliferate in response to PDGF, co-culture of fibrocytes stimulated the growth of lung fibroblasts through the production of PDGF-BB. In the lung of IPF patients, CD45+Collagen-I+FSP-1+ cells, which have a similar phenotype to fibrocytes, were detected and co-stained with anti-PDGF antibody. This study suggested that fibrocytes function in pulmonary fibrosis partly by producing PDGF in the lungs of IPF patients. J. Med. Invest. 67 : 102-112, February, 2020.

8.
J Vet Med Sci ; 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32418945

RESUMO

The lateral cytoplasmic processes of tenocytes extend to form three-dimensional network surrounding collagen fibers. It is unknown whether connections between two cytoplasmic processes involve overlapping of the processes or merely surface contact. In this study, the two-dimensional and three-dimensional structure of tenocytes in the Achilles tendons of the newly hatched chicks were studied using transmission electron microscopy and serial blocked face-scanning electron microscopy. Observation of the two-dimensional structures revealed various forms of cellular connections, including connections between the cytoplasmic processes of adjacent tenocytes and between the cytoplasmic process of tenocytes and fibroblasts. Three-dimensional observation showed spike-like cytoplasmic processes extending from one tenocyte that interlocked with cytoplasmic processes from other tenocytes. Cytoplasmic processes from each tenocyte within the chick tendons interlocked to ensure a tight cell-to-cell connection around growing collagen fibers. A cellular network formed by these cytoplasmic processes surrounds each collagen fiber. Cell-cell junctions, which were suggested to be gap junctions, observed at sites of cytoplasmic process overlap most likely represent the major route for communication between tenocytes associated with fibroblasts, enabling vital signals important for maintaining the cell and tendon integrity to be transmitted.

10.
Cell Mol Immunol ; 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32457406

RESUMO

Monoclonal antibodies (mAbs) are widely utilized as therapeutic drugs for various diseases, such as cancer, autoimmune diseases, and infectious diseases. Using the avian-derived B cell line DT40, we previously developed an antibody display technology, namely, the ADLib system, which rapidly generates antigen-specific mAbs. Here, we report the development of a human version of the ADLib system and showcase the streamlined generation and optimization of functional human mAbs. Tailored libraries were first constructed by replacing endogenous immunoglobulin genes with designed human counterparts. From these libraries, clones producing full-length human IgGs against distinct antigens can be isolated, as exemplified by the selection of antagonistic mAbs. Taking advantage of avian biology, effective affinity maturation was achieved in a straightforward manner by seamless diversification of the parental clones into secondary libraries followed by single-cell sorting, quickly affording mAbs with improved affinities and functionalities. Collectively, we demonstrate that the human ADLib system could serve as an integrative platform with unique diversity for rapid de novo generation and optimization of therapeutic or diagnostic antibody leads. Furthermore, our results suggest that libraries can be constructed by introducing exogenous genes into DT40 cells, indicating that the ADLib system has the potential to be applied for the rapid and effective directed evolution and optimization of proteins in various fields beyond biomedicine.

11.
Molecules ; 25(9)2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32365716

RESUMO

BACKGROUND: Gut microbiota plays a pivotal role in regulating host metabolism that affects the systemic health. To date, several studies have confirmed the fact that microbiota interacts with host, modulating immunity, controlling the homeostasis environment, and maintaining systemic condition. Recent studies have focused on the protective function of poly unsaturated fatty acids, 10-oxo-trans-11-oxadecenoic acid (KetoC) and 10-hydroxy-cis-12-octadecenoic acid (HYA), generated by gut microbiota on periodontal disease. Nevertheless, the mechanism remains unclear as investigations are limited to in vivo and in vitro studies. In this present review, we found that the administration of metabolites, KetoC and HYA, by a probiotic gut microbiota Lactobacillus plantarum from linoleic acid is found to inhibit the oxidation process, possess an antimicrobial function, and prevent the inflammation. These findings suggest the promising use of functional lipids for human health. CONCLUSION: Protective modalities of bioactive metabolites may support periodontal therapy by suppressing bacterial dysbiosis and regulating periodontal homeostasis in the clinical setting.

12.
J Clin Exp Hematop ; 60(1): 7-10, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32224564

RESUMO

Successful treatment of indolent T-cell lymphoproliferative disorder of the gastrointestinal tract (ITLPDGI) by chemotherapy is rare and watchful waiting is often performed for asymptomatic patients. We report a case of ITLPDGI successfully treated by involved field radiotherapy (IFRT). The patient presented with slow ITLPDGI localised to the stomach with mild symptoms. IFRT (30 Gy/20f) was administered, after which endoscopy revealed resolution of lesions and blood vessel appearance, and absence of proliferating abnormal lymphocytes was confirmed by biopsy. The patient remains lymphoma-free 1 year post-treatment. Although long-term follow-up and additional cases are essential for the evaluation of IFRT as a treatment option for localised ITLPDGL, complete remission after relatively low-dose IFRT is promising, particularly as this has been rarely achieved by chemotherapy.

13.
J Clin Oncol ; 38(18): 2053-2061, 2020 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-32343640

RESUMO

PURPOSE: This is a phase Ib trial of regorafenib plus nivolumab for gastric and colorectal cancer. PATIENTS AND METHODS: Enrolled patients received regorafenib plus nivolumab in a dose-finding part to estimate the maximum tolerated dose. Additional patients were enrolled in a dose-expansion part. Regorafenib of 80-160 mg was administered once daily for 21 days on/7 days off with nivolumab 3 mg/kg every 2 weeks. The primary end point was dose-limiting toxicity (DLT) during the first 4 weeks to estimate the recommended dose. RESULTS: Fifty patients (25 each with gastric and colorectal cancer) were enrolled. All patients had received ≥ 2 previous lines of chemotherapy, including anti-angiogenetic inhibitors in 96% of patients. Seven patients with gastric cancer had previously been treated with immune checkpoint inhibitors. One patient had microsatellite instability-high colorectal cancer, whereas the remaining patients had microsatellite stable or mismatch repair-proficient tumors. Three DLTs (grade 3 colonic perforation, maculopapular rash, and proteinuria) were observed with regorafenib 160 mg; none were observed with 80 or 120 mg. During the dose-expansion part, regorafenib dose was reduced from 120 to 80 mg because of frequent maculopapular rash. The common grade ≥ 3 treatment-related adverse events were rash (12%), proteinuria (12%), and palmar-plantar erythrodysesthesia (10%). Objective tumor response was observed in 20 patients (40%), including 11 with gastric cancer (44%) and 9 with colorectal cancer (36%). Median progression-free survival was 5.6 and 7.9 months in patients with gastric and colorectal cancer, respectively. CONCLUSION: The combination of regorafenib 80 mg plus nivolumab had a manageable safety profile and encouraging antitumor activity in patients with gastric and colorectal cancer, which warrants additional investigations in larger cohorts.

14.
Plant Mol Biol ; 103(3): 321-340, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32277429

RESUMO

Plants live in constantly changing and often unfavorable or stressful environments. Environmental changes induce biotic and abiotic stress, which, in turn, may cause genomic DNA damage. Hence, plants simultaneously suffer abiotic/biotic stress and DNA damage. However, little information is available on the signaling crosstalk that occurs between DNA damage and abiotic/biotic stresses. Arabidopsis thaliana SUPPRESSOR OF GAMMA RESPONSE1 (SOG1) is a pivotal transcription factor that regulates thousands of genes in response to DNA double-strand break (DSB), and we recently reported that SOG1 has a role in immune responses. In the present study, the effects of SOG1 overexpression on the DNA damage and immune responses were examined. Results found that SOG1 overexpression enhances the regulation of numerous downstream genes. Relative to the wild type plants, then, DNA damage responses were observed to be strongly induced. SOG1 overexpression also upregulates chitin (a major components of fungal cell walls) responsive genes in the presence of DSBs, implying that pathogen defense response is activated by DNA damage via SOG1. Further, SOG1 overexpression enhances fungal resistance. These results suggest that SOG1 regulates crosstalk between DNA damage response and the immune response and that plants have evolved a sophisticated defense network to contend with environmental stress.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Dano ao DNA/fisiologia , Regulação da Expressão Gênica de Plantas/fisiologia , Fatores de Transcrição/metabolismo , Apoptose/fisiologia , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Sequência de Bases , DNA de Plantas , Regulação da Expressão Gênica de Plantas/imunologia , Folhas de Planta/citologia , Ligação Proteica , Estresse Fisiológico , Fatores de Transcrição/genética
15.
Clin Chim Acta ; 507: 271-279, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32348784

RESUMO

BACKGROUND: Oxidative stress is now recognized to be an important therapeutic target in kidney diseases. However, there are currently no biomarkers that can be used clinically to diagnose renal oxidative stress. METHODS: A rapid assay system for urinary thioredoxin 1, an oxidative stress-dependent biomarker of acute kidney injury (AKI), was developed as a chemiluminescence enzyme immunoassay and validated analytically and clinically. RESULTS: Analytic evaluation revealed that hemolytic hemoglobin caused measurements to be abnormally high, above the detectable range. However, urine sediment containing red blood cells did not affect the measurements. Assays using our proposed chemiluminescence enzyme immunoassay were completed within as little as 6 min, whereas a conventional ELISA > 4 h. Aciduria

16.
Abdom Radiol (NY) ; 45(5): 1481-1487, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32285180

RESUMO

PURPOSE: Determine inter-observer variability among radiologists in assigning Cambridge Classification (CC) of chronic pancreatitis (CP) based on magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP) and contrast-enhanced CT (CECT). METHODS: Among 422 eligible subjects enrolled into the PROCEED study between 6/2017 and 8/2018, 39 were selected randomly for this study (chronic abdominal pain (n = 8; CC of 0), suspected CP (n = 22; CC of 0, 1 or 2) or definite CP (n = 9; CC of 3 or 4). Each imaging was scored by the local radiologist (LRs) and three of five central radiologists (CRs) at other consortium sites. The CRs were blinded to clinical data and site information of the participants. We compared the CC score assigned by the LR with the consensus CC score assigned by the CRs. The weighted kappa statistic (K) was used to estimate the inter-observer agreement. RESULTS: For the majority of subjects (34/39), the group assignment by LR agreed with the consensus composite CT/MRCP score by the CRs (concordance ranging from 75 to 89% depending on cohort group). There was moderate agreement (63% and 67% agreed, respectively) between CRs and LRs in both the CT score (weighted Kappa [95% CI] = 0.56 [0.34, 0.78]; p-value = 0.57) and the MR score (weighted Kappa [95% CI] = 0.68 [0.49, 0.86]; p-value = 0.72). The composite CT/MR score showed moderate agreement (weighted Kappa [95% CI] = 0.62 [0.43, 0.81]; p-value = 0.80). CONCLUSION: There is a high degree of concordance among radiologists for assignment of CC using MRI and CT.

17.
Leuk Res ; 91: 106336, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32151888

RESUMO

The 2017 WHO classification includes a new provisional entity of indolent T-lymphoproliferative disorders of the gastrointestinal tract (ITLPD-GIT). We investigated GI involvement of peripheral T-cell lymphoma (PTCL). Eighty-two patients were diagnosed with PTCL during 2007-2017. Eleven patients (13 %) had histologically-confirmed GI tract involvement {3 monomorphic epitheliotropic intestinal lymphoma (MEITL), 3 extranodal NK-/T-cell lymphoma nasal type (ENKL), 2 PTCL, not otherwise specified, 1 adult T-cell leukemia-lymphoma, 2 ITLPD-GIT}. Three patients each had lesions in the small intestine and multiple lesions, two each in the stomach and colon, and one in the duodenum. Six of the 11 patients remained alive. No perforation/stenosis was observed after chemo-radiotherapy, although one patient with ENKL developed gastric bleeding during chemotherapy. One patient with ITLPD-GIT (CD4-/CD8+/Ki67Low) with a colonic lesion showing diffuse edema and multiple aphtha by endoscope and diarrhea, initially diagnosed with MEITL, had active but stable disease after various chemotherapies for 1 year and no therapy for the next 5 years. Another patient with ITLPD-GIT (CD4+/CD8+/Ki67Low) with a localized gastric lesion and slight epigastralgia was in remission for 1 year after radiation. In conclusion, about 10 % of PTCLs were complicated by GI tract lesions and most had a poor prognosis. ITLPD-GIT should be considered as a differential diagnosis based on histology and clinical course. Local complications after chemo/radiotherapy in PTCL with GI involvement were not frequent.

18.
PLoS One ; 15(2): e0229262, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32092099

RESUMO

Recent studies have shown that colorectal serrated lesions, which include sessile serrated adenomas (SSAs) and traditional serrated adenomas (TSAs), are precursors of colorectal cancer. However, the molecular mechanisms underlying the carcinogenesis, particularly in TSAs, remain largely uncharacterized. To clarify their molecular and clinicopathological characteristics, we performed mutation and methylation analyses of cancer-associated genes in 78 serrated lesions, including TSAs, SSAs and microvesicular hyperplastic polyps. Target exon sequence analysis was performed with 39 genes, including genes known to be frequently mutated in colorectal cancers and/or serrated lesions. We also used bisulfite pyrosequencing to assess the methylation status of various cancer-associated genes and marker genes of the CpG island methylator phenotype (CIMP). The prevalence of mutations in genes associated with Wnt signaling was significantly higher in TSAs than SSAs (65% vs. 28%, p < 0.01). Among those, RNF43 mutations were observed in 38% of TSAs and 17% of SSAs. In immunohistochemical studies of 39 serrated lesions, the prevalence of abnormal nuclear ß-catenin accumulation was significantly higher in TSAs (57%) than SSAs (8%) (P = 0.01). SMOC1 methylation was detected in 54% of TSAs but in no SSAs (p < 0.01). Additionally, SMOC1 methylation was more prevalent among TSAs with KRAS mutation (82%) than with BRAF mutation (38%, p = 0.03). Lesions with CIMP-high or RNF43 mutations were detected only in TSAs with BRAF mutation, suggesting two distinct carcinogenic pathways in TSAs. Mutations in genes associated with Wnt signaling play a greater role in the carcinogenesis of TSAs than SSAs.


Assuntos
Adenoma/genética , Neoplasias Colorretais/genética , Mutação , Via de Sinalização Wnt/genética , Idoso , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Osteonectina/genética , Proteínas Proto-Oncogênicas B-raf , Proteínas Proto-Oncogênicas p21(ras)/genética
19.
Gastrointest Endosc ; 91(6): 1303-1309, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31958461

RESUMO

BACKGROUND AND AIMS: Pancreatic necrosis may be categorized as an acute necrotic collection (ANC) or walled-off necrosis (WON) based on complete encapsulation by a wall and collection age (≤4 weeks or >4 weeks). Endoscopic intervention of WON has become the standard of care, but little is known regarding the safety and efficacy of endoscopic intervention of pancreatic necrosis ≤4 weeks from disease onset. METHODS: Retrospective review of medical records and imaging studies of all patients undergoing early endoscopic intervention of pancreatic necrosis between 2008 and 2018 was carried out at 1 referral center. Patients who underwent previous interventional treatment were excluded. Control WON patients were matched to early intervention cases. The primary outcome was defined as resolution of the collection after endoscopic treatment, without surgery. RESULTS: Nineteen patients with early intervention were identified. The most common indication for intervention was infection. Median age of these collections at the time of initial endoscopic intervention was 23 days (range, 15-27 days), and all collections had a partial or complete wall discernable on contrast-enhanced CT. Eleven patients underwent concurrent endoscopic necrosectomy. The primary outcome was achieved in all patients in the early intervention group. Total duration of therapy was longer for early intervention compared with controls (103 vs 69 days, P = .042), with no mortality and similar adverse event rates compared with controls. CONCLUSIONS: Endoscopic intervention of pancreatic necrosis in the third and fourth weeks of illness appears effective and safe when a partial collection wall is present on cross-sectional imaging studies, with outcomes paralleling those reported for intervention of WON.

20.
AJR Am J Roentgenol ; 214(1): W37-W43, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31670591

RESUMO

OBJECTIVE. The purpose of this article is to evaluate the MR findings of prostatic remnant after prostatectomy and estimate the prevalence of prostatic remnant in patients that undergo MRI after prostatectomy. MATERIALS AND METHODS. Sixty-six patients who had undergone radical prostatectomy with pathologically proven benign prostatic remnant between 2007 and 2017 were retrospectively reviewed. Pathologically proven benign prostatic remnant was determined on the basis of initial pathologic report. Of the 66 initial patients, 30 patients with biopsy-proven benign prostatic remnant without coexisting recurrent prostate carcinoma and three patients who underwent repeat resection for completion prostatectomy were enrolled. MRI characteristics including location, size, signal intensity on T2-weighted images and DWI, and contrast enhancement pattern were analyzed. Nine additional patients were found to have a prostatic remnant by imaging without biopsy. The prevalence of prostatic remnant among those undergoing MRI for suspected recurrence during the same period was estimated. RESULTS. Prostatic remnant was detected in 23 of 33 patients on MRI. The remaining 10 patients did not have any visible abnormality. The 23 detected lesions were located in three regions: under the vesicourethral anastomosis in five patients, in the bladder neck in 12 patients, and posterior to the bladder in six patients. On T2-weighted imaging, 17 of 23 lesions showed heterogeneous hyperintensity. On DWI, 14 lesions showed hyperintensity. Dedicated MRI studies were performed for suspected prostate cancer recurrence in 2466 patients during the same period. Prevalence of exclusively benign prostate remnant detectable on MRI was approximately 1% of that population (23/2466-35/2466), and overall prevalence of any prostate remnant detectable on MRI was 3% (75/2466). CONCLUSION. Benign prostate remnant after prostatectomy occurs at three common sites and typically shows heterogeneous hyperintensity on T2-weighted imaging. The prevalence of detectable prostatic remnant in men who undergo MRI for suspected recurrence was approximately 1-3%.


Assuntos
Imagem por Ressonância Magnética , Próstata/diagnóstico por imagem , Próstata/cirurgia , Prostatectomia , Neoplasias da Próstata/cirurgia , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Próstata/patologia , Prostatectomia/métodos , Estudos Retrospectivos
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