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1.
J Med Virol ; 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32369204

RESUMO

During the clinical course of coronavirus disease 2019 (COVID-19), it has been observed that hepatic injury occurs in a significant proportion of patients, particularly in those with severe or critical illness. Mild increase in sinusoidal lymphocytic infiltration, sinusoidal dilatation, steatosis and multifocal hepatic necrosis are the pathologic changes reported. Direct viral-induced cellular injuries and potential hepatotoxicity from therapeutic drugs are two likely underlying mechanisms. In addition, the pre-existing chronic liver disease exacerbated during COVID-19, and COVID-19-related hyperinflammatory reactions may contribute to liver injury as well. Further studies of additional autopsy cases will help clarifying these possibilities.

2.
Pathol Res Pract ; : 152989, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32386774

RESUMO

OBJECTIVE: Some cases of solitary fibrous tumor (SFT) exhibit unusual histologic features that may cause diagnostic difficulty, such as fascicular monotonous spindle cells accompanied by hyalinized blood vessels and numerous evenly distributed mast cells, and features mimicking myxoid liposarcoma. Awareness of these features is important for reaching correct diagnosis of similar cases. METHODS: Three cases of SFT with the above unusual features were retrieved from our consult files for review, including H&E slides and immunohistochemical stains. In addition, FISH analysis for SS18-SSX (SYT), DDIT3 and MDM2 were performed. Furthermore, formalin-fixed paraffin-embedded (FFPE) tissue sections were tested for 8 fusion variants of NAB2-STAT6 by qualitative endpoint reverse-transcriptase (RT)-PCR. RESULTS: Neoplastic cells from all 3 cases are positive for CD34, CD99, and STAT6 immunohistochemically. In addition, the tumors are positive for NAB2-STAT6 fusion gene. Mast cells from the first case possess nonneoplastic phenotype and are positive for CD117 and tryptase staining but negative for CD25. CONCLUSIONS: The three cases studied here represent rare types of SFT, which differ from classical "pattern-less" pattern of SFT. Correct diagnosis required a combination of CD34 and STAT6 immunostaining and NAB2-STAT6 fusion gene analysis.

3.
Mod Pathol ; 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32291399

RESUMO

Data on pathologic changes of the 2019 novel coronavirus disease (COVID-19) are scarce. To gain knowledge about the pathology that may contribute to disease progression and fatality, we performed postmortem needle core biopsies of lung, liver, and heart in four patients who died of COVID-19 pneumonia. The patients' ages ranged from 59 to 81, including three males and one female. Each patient had at least one underlying disease, including immunocompromised status (chronic lymphocytic leukemia and renal transplantation) or other conditions (cirrhosis, hypertension, and diabetes). Time from disease onset to death ranged from 15 to 52 days. All patients had elevated white blood cell counts, with significant rise toward the end, and all had lymphocytopenia except for the patient with leukemia. Histologically, the main findings are in the lungs, including injury to the alveolar epithelial cells, hyaline membrane formation, and hyperplasia of type II pneumocytes, all components of diffuse alveolar damage. Consolidation by fibroblastic proliferation with extracellular matrix and fibrin forming clusters in airspaces is evident. In one patient, the consolidation consists of abundant intra-alveolar neutrophilic infiltration, consistent with superimposed bacterial bronchopneumonia. The liver exhibits mild lobular infiltration by small lymphocytes, and centrilobular sinusoidal dilation. Patchy necrosis is also seen. The heart shows only focal mild fibrosis and mild myocardial hypertrophy, changes likely related to the underlying conditions. In conclusion, the postmortem examinations show advanced diffuse alveolar damage, as well as superimposed bacterial pneumonia in some patients. Changes in the liver and heart are likely secondary or related to the underlying diseases.

5.
J Mol Neurosci ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152936

RESUMO

The purpose of this study was to evaluate the contribution of DNA methylation at the phospholipase A2 group VII (PLA2G7) gene, to the risk of developing brain arteriovenous malformations (BAVMs) and intracranial aneurysms (IAs) in a Han Chinese population. Seventy patients with BAVMs or IAs and 26 control subjects were recruited to evaluate PLA2G7 methylation by bisulfite pyrosequencing. CpG3 methylation at the PLA2G7 was significantly higher in BAVM patients than in the control group (Chr6,46735560, p = 0.042). Gender subgroup analysis showed that PLA2G7 CpG4 (Chr6,46735574, p = 0.033) and mean methylation (p = 0.037) levels were significantly associated with BAVM in males. However, in females, PLA2G7 methylations were much lower in IAs than in controls [CpG2 (Chr6,46735558), p = 0.030] and BAVMs [CpG2, p = 0.001; CpG4, p = 0.007; CpG6 (Chr6, 46735579), p = 0.024; mean, p = 0.013]. In addition, mean methylation of the PLA2G7 significantly correlated with apoB levels in all individuals (r = 0.288, p = 0.006), and with apoE in BAVM patients (r = 0.259, p = 0.016). The receiver operating characteristic (ROC) curve showed that PLA2G7 CpG3 methylation might be a predictor of BAVM risk in Han Chinese (area under curve (AUC) = 0.76, p = 0.008). PLA2G7 DNA methylation was significantly associated with the risk of developing BAVMs in males or IAs in females. Future studies on the PLA2G7 mechanisms should be performed on the pathogenesis of these cerebrovascular disorders.

6.
J Thorac Oncol ; 15(5): 700-704, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32114094

RESUMO

There is currently a lack of pathologic data on the novel coronavirus (severe acute respiratory syndrome coronavirus 2) pneumonia, or coronavirus disease 2019 (COVID-19), from autopsy or biopsy. Two patients who recently underwent lung lobectomies for adenocarcinoma were retrospectively found to have had COVID-19 at the time of the operation. These two cases thus provide important first opportunities to study the pathology of COVID-19. Pathologic examinations revealed that apart from the tumors, the lungs of both patients exhibited edema, proteinaceous exudate, focal reactive hyperplasia of pneumocytes with patchy inflammatory cellular infiltration, and multinucleated giant cells. Hyaline membranes were not prominent. Because both patients did not exhibit symptoms of pneumonia at the time of operation, these changes likely represent an early phase of the lung pathology of COVID-19 pneumonia.


Assuntos
Adenocarcinoma/cirurgia , Infecções por Coronavirus/complicações , Neoplasias Pulmonares/cirurgia , Pulmão/patologia , Pneumonia Viral/complicações , Adenocarcinoma/complicações , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Neoplasias Pulmonares/complicações , Masculino , Pandemias , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
7.
Int J Gynecol Pathol ; 39(2): 136-140, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32039937

RESUMO

Muir-Torre syndrome is a rare subtype of Lynch syndrome characterized by coincidence of skin neoplasm and visceral malignancies. Here, we report a case of this rare disease, whose diagnosis of the syndrome was first suspected by the pathologist. This was a 60-yr-old woman who presented with an axillary skin nodule, which was diagnosed as basal cell carcinoma. Further inquiry revealed that she was hospitalized for evaluation of a recurrent vaginal stump endometrial carcinoma. Histologic workup and immunohistochemistry for mismatch repair proteins of both the skin and vaginal tumor suggested the possibility of Muir-Torre syndrome. NexGen sequencing identified a frame-shift mutation in the MSH2 gene. The patient was found to have a metachronous colorectal carcinoma, uterine endometrial carcinoma, and skin cancer from 1998 to 2016. Five family members had also suffered from colorectal cancer or glioma. This case report illustrates the importance of the multidisciplinary care approach, mismatch repair protein and gene testing, and detailed medical history taking into consideration the diagnosis of Muir-Torre syndrome.

8.
JAMA Netw Open ; 3(2): e1921290, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32058557

RESUMO

Importance: Patients with locally advanced gastroesophageal adenocarcinoma (ie, stage ≥T3 and/or node positive) have high rates of recurrence despite surgery and adjunctive perioperative therapies, which also have high toxicity profiles. Evaluation of pharmacogenomically dosed perioperative gFOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and UGT1A1 genotype-directed irinotecan) to optimize efficacy while limiting toxic effects may have value. Objective: To evaluate the coprimary end points of margin-negative (R0) resection rates and pathologic response grades (PRGs) of gFOLFIRINOX therapy among patients with locally advanced gastroesophageal adenocarcinoma. Design, Setting, and Participants: This single-group phase 2 trial, conducted at 2 academic medical centers from February 2014 to March 2019, enrolled 36 evaluable patients with locally advanced adenocarcinoma of the esophagus, gastroesophageal junction, and gastric body. Data analysis was conducted in May 2019. Interventions: Patients received biweekly gFOLFIRINOX (fluorouracil, 2400 mg/m2 over 46 hours; oxaliplatin, 85 mg/m2; irinotecan, 180 mg/m2 for UGT1A1 genotype 6/6, 135 mg/m2 for UGT1A1 genotype 6/7, or 90 mg/m2 for UGT1A1 genotype 7/7; and prophylactic peg-filgastrim, 6 mg) for 4 cycles before and after surgery. Patients with tumors positive for ERBB2 also received trastuzumab (6-mg/kg loading dose, then 4 mg/kg). Main Outcomes and Measures: Margin-negative resection rate and PRG. Results: A total of 36 evaluable patients (27 [78%] men; median [range] age, 66 [27-85] years; 10 [28%] with gastric body cancer; 24 [67%] with intestinal-type tumors; 6 [17%] with ERBB2-positive tumors; 19 [53%] with UGT1A1 genotype 6/6; 16 [44%] with genotype 6/7; and 1 [3%] with genotype 7/7) were enrolled. Of these, 35 (97%) underwent surgery; 1 patient (3%) died after completing neoadjuvant chemotherapy while awaiting surgery. Overall, R0 resection was achieved in 33 of 36 patients (92%); 2 patients (6%) with linitis plastica achieved R1 resection. Pathologic response grades 1, 2, and 3 occurred in 13 patients (36%), 9 patients (25%), and 14 patients (39%), respectively, and PRG 1 was observed in 11 of 24 intestinal-type tumors (46%). Median disease-free survival was 30.1 months (95% CI, 15.0 months to not reached), and median overall survival was not reached (95% CI, 8.3 months to not reached). There were no differences in outcomes by UGT1A1 genotype group. A total of 38 patients, including 2 (5%) with antral tumors, were evaluable for toxic effects. Grade 3 or higher adverse events occurring in 5% or more of patients during the perioperative cycles included diarrhea (7 patients [18%]; 3 of 19 patients [16%] with genotype 6/6; 2 of 16 patients [13%] with genotype 6/7; 2 of 3 patients [67%] with genotype 7/7), anemia (2 patients [5%]), vomiting (2 patients [5%]), and nausea (2 patients [5%]). Conclusions and Relevance: In this study, perioperative pharmacogenomically dosed gFOLFIRINOX was feasible, providing downstaging with PRG 1 in more than one-third of patients and an R0 resection rate in 92% of patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02366819.

10.
Gene ; 730: 144266, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-31809837

RESUMO

INTRODUCTION: Small-cell variant of RO is a rare subtype of renal tumor that can be easily misdiagnosed. To date, only 20 cases had been reported, with its genetic alterations largely unknown due to insufficient information. MATERIALS AND METHODS: We report a case of the tumor with genetic characterization using exome sequencing chip. We also reviewed literature on this lesion to summarize clinicopathological presentation and differential diagnosis of the tumor. DISCUSSION: Grossly, the tumor is yellow to grayish brown, with clear boundary, central scar, or cystic degeneration. Microscopically, small-cell variant RO show scant eosinophilic cytoplasm with small-round nuclei, arranged in small acini and tubules. Nucleoli and necrosis are rarely observed. Immunohistochemically, the tumor is positive for EMA, cytokeratin 18, CD117 and E-cadherin. Genetically, 4745 differentially expressed genes in this tumor, which encode tricarboxylic acid cycle enzymes and are involved in mitochondrial respiratory chain. This result strongly supports the diagnosis of small cell variant of RO. Findings from the molecular genetic analysis of our case suggests that metabolic pathway-related genes (PIK3R5, PI3KCB, PLA2G4E, PLA2G2A, PLA2G6, PLCB4, PLCG2) may be exploited as potential targets for diagnosis and treatment when necessary. These genes may provide new clues for future research. CONCLUSION: Small-cell variant of RO is considered benign renal neoplasms with good prognosis. A histochemical and immunohistochemical stains assist in diagnosis of this tumor. Definitive diagnosis can help avoid unnecessary total renal nephrectomy. The exact mechanism of Small-cell variant of RO remains to be further investigated.

11.
Opt Express ; 27(20): 27618-27627, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31684526

RESUMO

Black phosphorus (BP), an emerging two-dimensional (2D) material with intriguing optical properties, forms a promising building block in optical and photonic devices. In this work, we propose a simple structure composed of a monolayer BP sandwiched by polymer and dielectric materials with low index contrast, and numerically demonstrate the perfect absorption mechanism via the critical coupling of guided resonances in the mid-infrared. Due to the inherent in-plane anisotropic feature of BP, the proposed structure exhibits highly polarization-dependent absorption characteristics, i.e., the optical absorption of the structure reaches 99.9% for TM polarization and only 3.2% for TE polarization at the same wavelength. Furthermore, the absorption peak and resonance wavelength can be flexibly tuned by adjusting the electron doping of BP, the geometrical parameters of the structure and the incident angles of light. Finally, the perfect absorption is also realized with the multilayer BP by simply adjusting the geometrical parameters. With high efficiency absorption, the remarkable anisotropy, flexible tunability, and easy-to-fabricate advantages, the proposed structure shows promising prospects in the design of polarization-selective and tunable high-performance devices in the mid-infrared, such as polarizers, modulators and photodetectors.

12.
Virchows Arch ; 2019 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-31422503

RESUMO

MFAP5, a 25-kD microfibril-associated glycoprotein that is involved in elastic microfibril assembly, has been demonstrated to be significantly downregulated in tumor stroma by previous gene expression study. The aim of this study was to confirm the reduced expression of MFAP5 in colonic tumor stroma using immunohistochemistry and to explore the utility of MFAP5 as a marker to facilitate diagnosing an invasive component versus pseudoinvasion in colon polyps. In all 19 colon cancer resection cases evaluated, while there was intact MFAP5 immunoreactivity in the uninvolved normal connective tissue, there was marked reduction of MFAP5 immunoreactivity in the desmoplastic stroma surrounding the invasive component. The difference in MFAP5 expression levels was most pronounced within the tumor, while a more heterogeneous expression pattern was observed at the tumor invasive front. Reduction of MFAP5 staining was also observed in the stroma around mucin pools in 6 out of 9 sections from mucinous adenocarcinomas and in areas with high-grade dysplasia. For the polypectomy cases, intact expression of MFAP5 was seen in the stroma surrounding the displaced adenomatous glands in 9 out of 12 polyps with pseudoinvasion. Loss of expression of MFAP5 was observed in the stroma surrounding small foci of invasive adenocarcinoma in 8 of 10 malignant polyps. MFAP5 is a useful marker that may help distinguish normal connective tissue from stroma within invasive colonic adenocarcinoma. MFAP5 may facilitate the distinction between pseudoinvasion and true invasive cancer in colonic adenomatous polyps with a sensitivity of 80% (confidence interval 44-96%) and a specificity of 75% (confidence interval 43-93%) in this small cohort.

13.
J Phys Condens Matter ; 31(46): 465002, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31425148

RESUMO

Photocatalytic water-splitting for hydrogen generation is a promising way to solve the energy crisis, yet the design of efficient photocatalysts is still a challenge. By utilization of first principles calculations, we predict the photocatalytic properties of monolayer boron phosphide (BP) based BP/XY2 (X = Mo, W; Y = S, Se) composites of different rotated configurations. Our results suggest that the BP/XY2 composites can be stably formed, and the narrowed bandgaps ensure these composites are suitable for absorbing visible light. The bandgaps and band edge positions are slightly affected by the rotation angles. The BP/MoS2, BP/MoSe2, and BP/WSe2 are type II heterostructures. Furthermore, the transferred charge from BP to XY2 layers leads to the formation of electric fields, which efficiently separate the photoinduced carriers. The band alignments of BP/MoS2, BP/MoS2, BP/MoSe2, and BP/WSe2 satisfy the requirements of overall water-splitting within the pH scope of 3.6-7.9, 6.8-7.9, 4.0-8.0, and 8.7-8.8. This work will provide valuable insight for designing efficient water-splitting photocatalysts.

14.
Am J Surg Pathol ; 43(9): 1253-1263, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31283632

RESUMO

Epstein-Barr virus (EBV) is a herpes virus that has been shown to contribute to the development of multiple tumor types. There are isolated reports on EBV infection in the gastrointestinal tract, but, notably, there are none with detailed descriptions of the morphologic features. It is believed to be difficult to generalize the histologic features, as EBV does not cause viral inclusions in infected cells. This study was aimed at describing the pathologic changes of nonlymphomatous gastrointestinal EBV lymphoproliferative diseases in both immunocompetent and immunocompromised settings; the former was focused on chronic active EBV infection, and the latter was about the infection in posttransplantation patients. A retrospective search identified a total of 26 cases of EBV lymphoproliferative disease in the gastrointestinal tract-8 in immunocompetent patients and 18 in immunocompromised patients. We found that there was no difference in pathologic findings in immunocompetent and immunocompromised patients, which ranged from essentially subtle to severe mucosal architectural distortion with prominent lymphoid aggregates. Most cases showed either focal or diffuse lymphocytic infiltration comprised of small to intermediate-sized lymphocytes with a round shape and increased cytoplasm when compared with mature small lymphocytes. Focal lymphoepithelial lesions and karyorrhexis can be seen. Although gastrointestinal primary EBV lymphoproliferative diseases are not common, the mortality is high. Awareness of the potential histologic features combined with suspicion of EBV infection from clinical presentation, radiographic findings, and/or EBV serologies can aid in the diagnosis of primary EBV infection in the gastrointestinal tract.

16.
Ann Surg Oncol ; 26(11): 3446-3454, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31240591

RESUMO

BACKGROUND: Controversy in axillary reverse mapping in axillary lymph node dissection (ALND) possibly results from incomplete recognition of the arm lymphatic system (ALS) and its compromise to oncological safety. The iDEntification and Preservation of ARm lymphaTic system (DEPART) technique facilitates complete identification of ALS; therefore, its use may decrease the occurrence of arm lymphedema. This study aimed to examine the arm lymphedema rate, locoregional recurrence, and feasibility to perform DEPART in ALND. METHODS: Patients from February 2013 to October 2017 from two tertiary referral centers were randomly assigned to two groups. In the study group, indocyanine green and methylene blue (MB) were utilized to identify arm sentinel nodes, and 0.1 ml MB was injected into the arm sentinel nodes to reveal the subsequent-echelon nodes and lymphatics. Gross arm lymph nodes were examined by intraoperative partial frozen section and were removed if positive. Arm lymphedema, local recurrence, regional recurrence, and distant metastasis were recorded at different follow-up examinations. RESULTS: Arm sentinel nodes were identified in 573 (83.2%) patients. Subsequent-echelon nodes and lymphatics were visualized in 558 (97.4%) patients. Metastatic arm nodes were identified in 38 (6.8%) patients. The arm lymphedema rate was 3.3% (18/543) in the study group versus 15.3% (99/648) in the control group (p < 0.001) after 37-month median follow-up. Regional recurrence showed no difference between the two groups (1.4% and 1.2%, respectively) (p = 0.392). CONCLUSIONS: DEPART can benefit breast cancer patients who undergo ALND, reducing the arm lymphedema rate without adversely affecting the morbidity of regional recurrence.


Assuntos
Braço/cirurgia , Neoplasias da Mama/cirurgia , Linfonodos/cirurgia , Sistema Linfático , Linfedema/prevenção & controle , Recidiva Local de Neoplasia/cirurgia , Tratamentos com Preservação do Órgão/métodos , Adulto , Idoso , Braço/patologia , Axila , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/patologia , Carcinoma Lobular/cirurgia , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Prospectivos , Procedimentos Cirúrgicos Reconstrutivos
17.
Hum Pathol ; 89: 44-50, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31054900

RESUMO

Inflammatory bowel disease-associated colorectal carcinomas (IBD-CRCs) develop in a background of chronic inflammation, and thus, the molecular landscape of these tumors likely differs from that of sporadic colorectal cancer. To add to emerging data on molecular alterations present in these tumors, we analyzed our institution's cohort of IBD-CRCs. CRCs resected from patients with IBD underwent molecular analysis via a 50-gene hot-spot solid tumor panel (OncoScreen ST2.0). In-house sporadic CRCs and The Cancer Genome Atlas project data were used for comparison. Fifty-five IBD-CRCs from 48 patients were successfully analyzed. Mutations in TP53 were most common and were present in 69% of IBD-CRCs; a similar percentage of TP53 mutations was detected in sporadic colorectal carcinomas (70%). APC and KRAS mutations were significantly less common in IBD-CRCs than in sporadic CRCs (15% versus 53%, P < .001 and 20% versus 38%, P = .02, respectively). Additionally, the potentially targetable IDH1 R132 mutation was present in 7% of IBD-CRCs but only 1% of sporadic CRCs and The Cancer Genome Atlas CRCs; alterations in other genes with potential targeted therapies were very rare. In conclusion, IBD-CRCs exhibit molecular differences when compared to sporadic CRCs, suggesting different pathways of carcinogenesis, although certain alterations are common to both types of tumors. IDH1 mutations are present in a subset of IBD-CRCs, which may expand therapeutic options in the future.

18.
Medicine (Baltimore) ; 98(17): e15323, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31027102

RESUMO

RATIONALE: Indolent T-cell lymphoproliferative disease (T-LPD) of gastrointestinal tract is a rare recently described disease that seldom progresses. We report a case of T-LPD with synchronous diffuse large B-cell lymphoma (DLBCL) that cause aggravation of disease. PATIENT CONCERNS: A 46-year-old Chinese male presented with intermittent paraumbilical colic pain, bloating, and occasional diarrhea for 10 years. His condition aggravated with partial bowel obstruction recently. The patient was diagnosed as T-LPD initially based on histological result and T-cell receptor-gamma clonal gene rearrangement test. The patient was followed without chemotherapy. His condition stabilized for 1 year and then deteriorated with small intestine perforation. DIAGNOSIS: The patient was diagnosed as indolent T-LPD and DLBCL finally. INTERVENTIONS: The patient had surgery for intestine perforation and received chemotherapy for DLBCL and T-LPD afterward. OUTCOMES: At 6 months follow-up, the patient continued to have resolution of his symptoms. LESSONS: Early detection of high-grade transformation of T-LPD or the coexistence of aggressive lymphoma is essential for the patient. DLBCL may coexist in the indolent course of T-LPD. The diagnosis of T-LPD should be made cautiously in case with progressing symptoms such as intestinal obstruction.


Assuntos
Linfoma Difuso de Grandes Células B/complicações , Transtornos Linfoproliferativos/complicações , Antineoplásicos/uso terapêutico , Humanos , Perfuração Intestinal/complicações , Perfuração Intestinal/cirurgia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Linfócitos T
19.
Micromachines (Basel) ; 10(3)2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-30889845

RESUMO

The optical performance of a periodically tunable plasma perfect metamaterial absorber based on a square-square-circle array we propose in the terahertz region is analyzed in this work by the finite difference time domain (FDTD) method. We not only discuss the impact of various parameters such as period a, length L, radius R, and incident angle θ under transverse magnetic (TM)- and transverse electric (TE)-polarization on the absorption spectra of the absorber but also study the effect of the Fermi energy EF and relaxation time τ. Finally, we simulate the spectra as the surrounding refractive index n changes to better evaluate the sensing performance of the structure, producing a sensitivity S of the structure of up to 15006 nm/RIU. On account of this research, we find that the absorber is beneficial to sensors and detectors in the terahertz region.

20.
Gastroenterology ; 156(8): 2297-2312, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30836096

RESUMO

BACKGROUND & AIMS: Interleukin 6 (IL6) and tumor necrosis factor contribute to the development of colitis-associated cancer (CAC). We investigated these signaling pathways and the involvement of G protein subunit alpha i1 (GNAI1), GNAI2, and GNAI3 in the development of CAC in mice and humans. METHODS: B6;129 wild-type (control) or mice with disruption of Gnai1, Gnai2, and/or Gnai3 or conditional disruption of Gnai2 in CD11c+ or epithelial cells were given dextran sulfate sodium (DSS) to induce colitis followed by azoxymethane (AOM) to induce carcinogenesis; some mice were given an antibody against IL6. Feces were collected from mice, and the compositions of microbiomes were analyzed by polymerase chain reactions. Dendritic cells (DCs) and myeloid-derived suppressor cells (MDSCs) isolated from spleen and colon tissues were analyzed by flow cytometry. We performed immunoprecipitation and immunoblot analyses of colon tumor tissues, MDSCs, and mouse embryonic fibroblasts to study the expression levels of GNAI1, GNAI2, and GNAI3 and the interactions of GNAI1 and GNAI3 with proteins in the IL6 signaling pathway. We analyzed the expression of Gnai2 messenger RNA by CD11c+ cells in the colonic lamina propria by PrimeFlow, expression of IL6 in DCs by flow cytometry, and secretion of cytokines in sera and colon tissues by enzyme-linked immunosorbent assay. We obtained colon tumor and matched nontumor tissues from 83 patients with colorectal cancer having surgery in China and 35 patients with CAC in the United States. Mouse and human colon tissues were analyzed by histology, immunoblot, immunohistochemistry, and/or RNA-sequencing analyses. RESULTS: GNAI1 and GNAI3 (GNAI1;3) double-knockout (DKO) mice developed more severe colitis after administration of DSS and significantly more colonic tumors than control mice after administration of AOM plus DSS. Development of increased tumors in DKO mice was not associated with changes in fecal microbiomes but was associated with activation of nuclear factor (NF) κB and signal transducer and activator of transcription (STAT) 3; increased levels of GNAI2, nitric oxide synthase 2, and IL6; increased numbers of CD4+ DCs and MDSCs; and decreased numbers of CD8+ DCs. IL6 was mainly produced by CD4+/CD11b+, but not CD8+, DCs in DKO mice. Injection of DKO mice with a blocking antibody against IL6 reduced the expansion of MDSCs and the number of tumors that developed after CAC induction. Incubation of MDSCs or mouse embryonic fibroblasts with IL6 induced activation of either NF-κB by a JAK2-TRAF6-TAK1-CHUK/IKKB signaling pathway or STAT3 by JAK2. This activation resulted in expression of GNAI2, IL6 signal transducer (IL6ST, also called GP130) and nitric oxide synthase 2, and expansion of MDSCs; the expression levels of these proteins and expansion of MDSCs were further increased by the absence of GNAI1;3 in cells and mice. Conditional disruption of Gnai2 in CD11c+ cells of DKO mice prevented activation of NF-κB and STAT3 and changes in numbers of DCs and MDSCs. Colon tumor tissues from patients with CAC had reduced levels of GNAI1 and GNAI3 and increased levels of GNAI2 compared with normal tissues. Further analysis of a public human colorectal tumor DNA microarray database (GSE39582) showed that low Gani1 and Gnai3 messenger RNA expression and high Gnai2 messenger RNA expression were significantly associated with decreased relapse-free survival. CONCLUSIONS: GNAI1;3 suppresses DSS-plus-AOM-induced colon tumor development in mice, whereas expression of GNAI2 in CD11c+ cells and IL6 in CD4+/CD11b+ DCs appears to promote these effects. Strategies to induce GNAI1;3, or block GNAI2 and IL6, might be developed for the prevention or therapy of CAC in patients.


Assuntos
Transformação Celular Neoplásica/genética , Colite/patologia , Neoplasias do Colo/patologia , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/genética , Animais , Biópsia por Agulha , Carcinogênese , Colite/genética , Neoplasias do Colo/genética , Modelos Animais de Doenças , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Imuno-Histoquímica , Interleucina-16/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Distribuição Aleatória , Valores de Referência , Sensibilidade e Especificidade , Transdução de Sinais/genética
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