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1.
Immunity ; 51(3): 522-534.e7, 2019 09 17.
Artículo en Inglés | MEDLINE | ID: mdl-31471107

RESUMEN

Although recent progress provides mechanistic insights into the pathogenesis of pulmonary fibrosis (PF), rare anti-PF therapeutics show definitive promise for treating this disease. Repeated lung epithelial injury results in injury-repairing response and inflammation, which drive the development of PF. Here, we report that chronic lung injury inactivated the ubiquitin-editing enzyme A20, causing progressive accumulation of the transcription factor C/EBPß in alveolar macrophages (AMs) from PF patients and mice, which upregulated a number of immunosuppressive and profibrotic factors promoting PF development. In response to chronic lung injury, elevated glycogen synthase kinase-3ß (GSK-3ß) interacted with and phosphorylated A20 to suppress C/EBPß degradation. Ectopic expression of A20 or pharmacological restoration of A20 activity by disturbing the A20-GSK-3ß interaction accelerated C/EBPß degradation and showed potent therapeutic efficacy against experimental PF. Our study indicates that a regulatory mechanism of the GSK-3ß-A20-C/EBPß axis in AMs may be a potential target for treating PF and fibroproliferative lung diseases.


Asunto(s)
Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Macrófagos/metabolismo , Fibrosis Pulmonar/metabolismo , Factores de Transcripción/metabolismo , Ubiquitina/metabolismo , Animales , Línea Celular , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Células HEK293 , Humanos , Inflamación/metabolismo , Ratones , Ratones Endogámicos C57BL , Fosforilación/fisiología , Transducción de Señal/fisiología , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación/fisiología , Regulación hacia Arriba/fisiología
2.
Oncologist ; 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38907674

RESUMEN

BACKGROUND: Tumor microenvironment (TME) characteristics including tumor stroma ratio (TSR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs) were examined in resected gastric cancer. These TME features have been shown to indicate metastatic potential in colon cancer, and intestinal-type gastric cancer (IGC) has pathological similarities with that malignancy. METHODS: TSR, TB, and TILs were quantified in routine histological sections from 493 patients with IGC who underwent radical resection at 2 university hospitals in China from 2010 to 2016. TME variables were dichotomized as follows: TSR (50%), TILs (median), TB per international guidelines (4 buds/0.785mm2), and platelet-lymphocyte ratio (PLR) per survival ROC. Association of TME features with patient clinicopathological characteristics, time-to-recurrence (TTR), and cancer-specific-survival (CSS) were examined using univariate and multivariate analysis, including a relative contribution analysis by Cox regression. RESULTS: Patients whose tumors showed high TSR or high TB or low TILs were each significantly associated with increased T and N stage, higher histological grade, and poorer TTR and CSS at 5 years. Only TSR and N stage were independently associated with TTR and CSS after adjustment for covariates. PLR was only independently associated with TTR after adjustment for covariates. Among the variables examined, only TSR was significantly associated with both TTR (HR 1.72, 95% CI, 1.14-2.60, P = .01) and CSS (HR 1.62, 95% CI, 1.05-2.51, P = .03) multivariately. Relative contribution to TTR revealed that the top 3 contributors were N stage (45.1%), TSR (22.5%), and PLR (12.9%), while the top 3 contributors to CSS were N stage (59.9%), TSR (14.7%), and PLR (10.9%). CONCLUSIONS: Among the examined TME features, TSR was the most robust for prognostication and was significantly associated with both TTR and CSS. Furthermore, the relative contribution of TSR to patient TTR and CSS was second only to nodal status.

3.
Neuropathology ; 37(6): 485-494, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28643854

RESUMEN

Olfactory dysfunction is among the signs of Alzheimer's disease (AD) and cognitive impairment. It has been demonstrated Aß was associated with olfactory impairment observed in both transgenic mice and in AD patients. In this study, we evaluated amyloid deposition in the olfactory circuit of APP/PS1 transgenic mouse model of AD, which showed olfactory dysfunction in olfactory behavior tests. We found amyloid depositions were widely distributed in the whole olfactory circuit. Moreover, we think these amyloid depositions contribute to neuronal atrophy, dendritic abnormalities, synapse loss and axonal degeneration. Therefore, there was a correlation between olfactory deficits and amyloid deposition. Our findings provide initial insights into the pathological basis of AD-related olfactory dysfunction.


Asunto(s)
Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/patología , Trastornos del Olfato/etiología , Trastornos del Olfato/patología , Precursor de Proteína beta-Amiloide/genética , Animales , Encéfalo/patología , Modelos Animales de Enfermedad , Humanos , Ratones , Ratones Transgénicos , Mucosa Olfatoria/patología , Placa Amiloide/patología , Presenilina-1/genética
4.
Fetal Pediatr Pathol ; 35(6): 410-415, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27362946

RESUMEN

We describe two children with ganglioneuroma (GN) likely originating from incompletely resected neuroblastoma (NB) during infancy, stages 2A and 2B, who did not undergo postoperative adjuvant chemotherapies. Both NB tumors had no MYCN amplification, had TrKA but no TrkB expression, and by TUNEL had apoptosis. These findings may have contributed to spontaneous maturation of the residual primary NB and hence the favorable prognosis, which suggests surgery alone might be the sufficient initial therapy for low-risk patients.


Asunto(s)
Diferenciación Celular/fisiología , Ganglioneuroma/patología , Regulación Neoplásica de la Expresión Génica/genética , Neuroblastoma/patología , Biomarcadores de Tumor/metabolismo , Femenino , Ganglioneuroma/diagnóstico , Amplificación de Genes/fisiología , Humanos , Lactante , Neuroblastoma/diagnóstico , Proteínas Proto-Oncogénicas c-myc/metabolismo
5.
J BUON ; 20(5): 1327-36, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26537082

RESUMEN

PURPOSE: To evaluate the anticancer effect of chrysin and its additive combination with low-dose cisplatin in human glioma (U87) cancer cells and to study its underlying mechanism. METHODS: Inverted phase and fluorescence microscopic studies were done to demonstrate the effect of chrysin and its combination with cisplatin on cellular morphology and apoptosis. Annexin V-FITC assay was used to quantify the extent of apoptosis in chrysin and chrysin+cisplatin treated cells. Flow cytometry using propidium iodide (PI) as a staining agent was used to study the effect of chrysin and its combination with cisplatin on cell cycle phase distribution. RESULTS: The results showed chrysin brought about a potent and dose-dependent antiproliferative effect in human glioma cancer cells. However, the combination of chrysin with low dose cisplatin led to a much higher growth inhibitory effects indicating an additive effect between the two compounds. The combined effect of chrysin and cisplatin also gave rise to a greater apoptosis induction as well as cell cycle arrest in comparison to the treatment by chrysin or cisplatin alone. Fluorescence microscopy as well as inverted phase contrast microscopy also revealed that the combination of chrysin plus cisplatin resulted in greater apoptosis induction as well as cell morphology alterations. Combination treatment of chrysin and cisplatin resulted in greater percentage of cells in early as well as in late apoptotic stages. The combination effect was also seen in mitochondrial membrane potential loss. CONCLUSION: Chrysin additively potentiates the antiproliferative, cell cycle arrest and apoptotic activity of cisplatin in human glioma cancer (U87) cells.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Cisplatino/farmacología , Flavonoides/farmacología , Glioma/tratamiento farmacológico , Neoplasias Encefálicas/patología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Glioma/patología , Humanos
6.
Cell Mol Neurobiol ; 34(6): 805-12, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24939432

RESUMEN

Alzheimer's disease (AD) is a very common progressive neurodegenerative disorder affecting the learning and memory abilities in the brain. Key findings from recent studies of epigenetic mechanisms of memory suggest chromatin remodeling disorders via histone hypoacetylation of the lysine residue contribute to the cognitive impairment in AD. Therefore, the deinhibition of histone acetylation induced by histone deacetylases (HDACs) inhibitors contributes to recovery of learning and memory. We show here that the antiepileptic drug sodium valproate (VPA) potently enhanced long-term recognition memory and spatial learning and memory in AD transgenic mice. Possible mechanisms showed VPA could significantly elevate histone acetylation through HDACs activity inhibition and increase plasticity-associated gene expression within the hippocampi of mice. Our study suggests that VPA, serving as a HDACs inhibitor, can be considered as a potential pharmaceutical agent for the improvement of cognitive function in AD.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Trastornos de la Memoria/tratamiento farmacológico , Memoria/efectos de los fármacos , Ácido Valproico/farmacología , Enfermedad de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Modelos Animales de Enfermedad , Memoria/fisiología , Trastornos de la Memoria/metabolismo , Ratones Endogámicos C57BL , Ratones Transgénicos
7.
Chin J Integr Med ; 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38570473

RESUMEN

OBJECTIVE: To investigate whether Naoxueshu Oral Liquid (NXS) could promote hematoma absorption in post-craniotomy hematoma (PCH) patients. METHODS: This is an open-label, multicenter, and randomized controlled trial conducted at 9 hospitals in China. Patients aged 18-80 years with post-craniotomy supratentorial hematoma volume ranging from 10 to 30 mL or post-craniotomy infratentorial hematoma volume less than 10 mL, or intraventricular hemorrhage following cranial surgery were enrolled. They were randomly assigned at a 1:1 ratio to the NXS (10 mL thrice daily for 15 days) or control groups using a randomization code table. Standard medical care was administered in both groups. The primary outcome was the percentage reduction in hematoma volume from day 1 to day 15. The secondary outcomes included the percentage reduction in hematoma volume from day 1 to day 7, the absolute reduction in hematoma volume from day 1 to day 7 and 15, and the change in neurological function from day 1 to day 7 and 15. The safety was closely monitored throughout the study. Moreover, subgroup analysis was performed based on age, gender, history of diabetes, and etiology of intracerebral hemorrhage (ICH). RESULTS: A total of 120 patients were enrolled and randomly assigned between March 30, 2018 and April 15, 2020. One patient was lost to follow-up in the control group. Finally, there were 119 patients (60 in the NXS group and 59 in the control group) included in the analysis. In the full analysis set (FAS) analysis, the NXS group had a greater percentage reduction in hematoma volume from day 1 to day 15 than the control group [median (Q1, Q3): 85% (71%, 97%) vs. 76% (53%, 93%), P<0.05]. The secondary outcomes showed no statistical significance between two groups, either in FAS or per-protocol set (P>0.05). Furthermore, no adverse events were reported during the study. In the FAS analysis, the NXS group exhibited a higher percentage reduction in hematoma volume on day 15 in the following subgroups: male patients, patients younger than 65 years, patients without diabetes, or those with initial cranial surgery due to ICH (all P<0.05). CONCLUSIONS: The administration of NXS demonstrated the potential to promote the percentage reduction in hematoma volume from day 1 to day 15. This intervention was found to be safe and feasible. The response to NXS may be influenced by patient characteristics. (Registration No. ChiCTR1800017981).

9.
Front Oncol ; 13: 1194232, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37529690

RESUMEN

Background: Lynch syndrome (LS)-associated glioblastoma (GBM) is rare in clinical practice, and simultaneous occurrence with cutaneous porokeratosis is even rarer. In this study, we analyzed the clinicopathological and genetic characteristics of LS-associated GBMs and concurrent porokeratosis, as well as evaluated the tumor immune microenvironment (TIME) of LS-associated GBMs. Methods: Immunohistochemical staining was used to confirm the histopathological diagnosis, assess MMR and PD-1/PD-L1 status, and identify immune cell subsets. FISH was used to detect amplification of EGFR and PDGFRA, and deletion of 1p/19q and CDKN2A. Targeted NGS assay analyzed somatic variants, MSI, and TMB status, while whole-exome sequencing and Sanger sequencing were carried out to analyze the germline mutations. Results: In the LS family, three members (I:1, II:1 and II:4) were affected by GBM. GBMs with loss of MSH2 and MSH6 expression displayed giant and multinucleated bizarre cells, along with mutations in ARID1A, TP53, ATM, and NF1 genes. All GBMs had TMB-H but not MSI-H. CD8+ T cells and CD163+ macrophages were abundant in each GBM tissue. The primary and recurrent GBMs of II:1 showed mesenchymal characteristics with high PD-L1 expression. The family members harbored a novel heterozygous germline mutation in MSH2 and FDPS genes, confirming the diagnosis of LS and disseminated superficial actinic porokeratosis. Conclusion: LS-associated GBM exhibits heterogeneity in clinicopathologic and molecular genetic features, as well as a suppressive TIME. The presence of MMR deficiency and TMB-H may serve as predictive factors for the response to immune checkpoint inhibitor therapy in GBMs. The identification of LS-associated GBM can provide significant benefits to both patients and their family members, including accurate diagnosis, genetic counseling, and appropriate screening or surveillance protocols. Our study serves as a reminder to clinicians and pathologists to consider the possibility of concurrent genetic syndromes in individuals or families.

10.
Front Immunol ; 14: 1269097, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38022513

RESUMEN

Urothelial carcinoma (UC) with deficient mismatch repair (dMMR) is a specific subtype of UC characterized by the loss of mismatch repair (MMR) proteins and its association with Lynch syndrome (LS). However, comprehensive real-world data on the incidence, clinicopathological characteristics, molecular landscape, and biomarker landscape for predicting the efficacy of PD-1/PD-L1 inhibitors in the Chinese patients with dMMR UC remains unknown. We analyzed 374 patients with bladder urothelial carcinoma (BUC) and 232 patients with upper tract urothelial carcinoma (UTUC) using tissue microarrays, immunohistochemistry, and targeted next-generation sequencing. Results showed the incidence of dMMR UC was higher in the upper urinary tract than in the bladder. Genomic analysis identified frequent mutations in KMT2D and KMT2C genes and LS was confirmed in 53.8% of dMMR UC cases. dMMR UC cases displayed microsatellite instability-high (MSI-H) (PCR method) in 91.7% and tumor mutational burden-high (TMB-H) in 40% of cases. The density of intratumoral CD8+ T cells correlated with better overall survival in dMMR UC patients. Positive PD-L1 expression was found in 20% cases, but some patients positively responded to immunotherapy despite negative PD-L1 expression. Our findings provide valuable insights into the characteristics of dMMR UC in the Chinese population and highlights the relevance of genetic testing and immunotherapy biomarkers for treatment decisions.


Asunto(s)
Carcinoma de Células Transicionales , Neoplasias Colorrectales Hereditarias sin Poliposis , Neoplasias de la Vejiga Urinaria , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/genética , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Receptor de Muerte Celular Programada 1/genética , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Reparación de la Incompatibilidad de ADN/genética , Pueblos del Este de Asia , Neoplasias Colorrectales Hereditarias sin Poliposis/genética
11.
Cell Mol Neurobiol ; 32(8): 1337-42, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22733364

RESUMEN

As one part of epigenetics, histone deacetylases (HDACs) have been demonstrated to get into the neural events, including neurogenesis, synaptic plasticity, and neurodegeneration through regulating acetylation status of target proteins to influence protein function and gene expression. However, the recent studies indicated that HDAC2, a member of HDACs family, played a role in insulin signaling pathway and synaptic plasticity. Here, we are concerned about whether HDAC2 was co-located with insulin signaling components in postsynaptic glutamatergic neurons (PSGNs) of the adult mouse hippocampus using double immunofluorescence staining. The results displayed that HDAC2 was present in PSGNs marked by N-methyl-D-aspartate receptor subunit 2B, in which major components of insulin signaling pathway such as insulin receptor alpha and beta and insulin receptor substrate-1 were also involved. Accordingly, we speculate that the interaction of HDAC2 and insulin signaling system in PSGNs observed in the present study may serve as a potential mechanism in memory formation. We hope this could provide a valuable basis for understanding the roles of HDAC2 and insulin on cognitive impairment of diabetes mellitus, involved Alzheimer's disease, which is also called type 3 diabetes recently. And this will also benefit to the treatment of insulin-related diseases in the central nervous system.


Asunto(s)
Hipocampo/metabolismo , Histona Desacetilasa 2/biosíntesis , Insulina/biosíntesis , Transducción de Señal/fisiología , Factores de Edad , Animales , Ácido Glutámico/análisis , Ácido Glutámico/biosíntesis , Hipocampo/química , Histona Desacetilasa 2/análisis , Insulina/análisis , Masculino , Ratones , Ratones Endogámicos C57BL
12.
Pathol Oncol Res ; 28: 1610638, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36338826

RESUMEN

Immune checkpoint inhibitors (ICIs) have shown encouraging outcomes against Lynch syndrome (LS)-associated colorectal cancer (CRC) and endometrial cancer with mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H). However, there is as yet no clarity on the safety and efficacy of immunotherapy combined with chemotherapy in LS-associated urothelial carcinoma (UC). Here, we report a patient with recurrent and metastatic LS-associated UC who achieved sustained response to programmed death protein 1 (PD-1) inhibitor combined with chemotherapy over 31 months, during which the side effects of immunotherapy could be controlled and managed. Our findings indicate that the dMMR/MSI status and PD-1 expression in UC may have potential predictive value for the response to PD-1-targeted immunotherapy. Our case supports the inclusion of such combination and/or monotherapy for UC in clinical studies and using dMMR/MSI status and PD-1 expression as potential predictive biomarkers for assessment of the therapeutic response.


Asunto(s)
Carcinoma de Células Transicionales , Neoplasias Colorrectales Hereditarias sin Poliposis , Neoplasias Colorrectales , Neoplasias de la Vejiga Urinaria , Femenino , Humanos , Inestabilidad de Microsatélites , Receptor de Muerte Celular Programada 1 , Reparación de la Incompatibilidad de ADN , Carcinoma de Células Transicionales/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Inmunoterapia , Neoplasias Colorrectales/patología
13.
Sci Total Environ ; 767: 144340, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-33429273

RESUMEN

Phragmites australis and Chloris virgata are native, dominant, salt-tolerant grass species that grow in the Yellow River Delta, China, and have potential applications in the phytoremediation of petroleum-polluted saline soil. The characteristics of endophytic bacterial communities of Phragmites australis and Chloris virgata and their functions in hydrocarbon degradation and plant growth promotion have been studied using both high-throughput sequencing and conventional microbial techniques. Through 16S rRNA gene amplicon sequencing, we found five bacterial phyla that were dominant among the endophytic bacterial communities of the two grass species, including Proteobacteria, Actinobacteria, Firmicutes, Bacteroidetes, and Tenericutes. The phylum Proteobacteria was common among the endophytic bacterial communities of the two grass species. The diversity in the endophytic bacterial community of Chloris virgata was generally higher than that in the community of Phragmites australis. Thirty-eight hydrocarbon-degrading endophytic bacteria were isolated from the two grasses via culturing techniques. Based on phylogenetic analyses, the bacterial isolates were classified into the phyla Proteobacteria, Firmicutes, and Actinobacteria. The majority of strains belonged to the genera Bacillus and Pseudomonas. More than 70% of the isolates of hydrocarbon-degrading endophytes exhibited the ability to stimulate plant growth. These isolates mainly belonged to Bacillus sp., Pseudomonas sp., Beijerinckia sp., Serratia sp., Acinetobacter sp., Microbacterium sp., and Rhizobium sp. Altogether, the present study revealed that Phragmites australis and Chloris virgata growing on petroleum-polluted saline soil in the Yellow River Delta harbor several diverse species of endophytic bacteria and serve as novel sources of beneficial bacteria and hydrocarbon degradation.


Asunto(s)
Poaceae , Ríos , Bacterias/genética , China , Filogenia , ARN Ribosómico 16S/genética
14.
Diagn Pathol ; 16(1): 14, 2021 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-33612108

RESUMEN

BACKGROUND: Succinate dehydrogenase deficient gastrointestinal stromal tumors (SDH-deficient GISTs), which lack KIT or PDGFRA mutations demonstrate unique clinical and pathological features, and they respond poorly to standard targeted therapy. We herein present a novel case of SDH-deficient GIST in a three-month-old infant's colon mesentery, and he is the youngest patientto date. CASE PRESENTATION: The infantpresented with complaints of blood in the stool. CT showed a 6.3 × 4.6 cm mass in the left lower retroperitoneal. Complete resection of tumor and segmental bowel resection was performed without regional lymphadenectomy. Histologically, tumor cells were distinctive in their multinodular colon wall involvement with interspersed tracts of colon wall smooth muscle. The tumor was composed mainly of epithelioid cells. Immunohistochemically, the tumor cells were positive for Vim, CD117, PDGFR, while negative for SDHB. Mutational analysis showed a synonymous mutation for SDHB and wild-type for KIT and PDGFRA. Two months after surgery, metastases were found and Imatinib was administered. Unfortunately, the disease continued to progress, and the infant died 5 months after surgery. CONCLUSIONS: SDH-deficient GISTs comprise a subgroup of a relatively rare tumor type and show a number of clinically and biologically unique features, especially for infants. It is of great importance to developing new therapeutic targets and novel specific drugs.


Asunto(s)
Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/patología , Succinato Deshidrogenasa/deficiencia , Análisis Mutacional de ADN/métodos , Tumores del Estroma Gastrointestinal/diagnóstico , Mutación de Línea Germinal , Humanos , Lactante , Mutación/genética , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/metabolismo , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Succinato Deshidrogenasa/metabolismo
15.
J Cancer Res Ther ; 17(3): 790-796, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34269315

RESUMEN

OBJECTIVES: The objective of the study is to provide an efficient and practical screening strategy to distinguish a broader spectrum of Lynch syndrome (LS) and LS mimics-associated colorectal cancer (CRC), including Lynch-like syndrome (LLS), constitutional mismatch repair-deficiency, familial CRC type X (FCCTX), and polymerase proofreading-associated polyposis syndrome. MATERIALS AND METHODS: 1294 cases of CRC samples were detected mismatch repair (MMR) status using immunohistochemistry (IHC) staining, in which the cases with MLH1-deficient CRC underwent BRAF mutation analysis by IHC. Following the personal and/or family history survey, next-generation sequencing (NGS) was used to detect gene variants. RESULTS: 1294 CRC patients were dichotomized into tumors caused by a deficient MMR (dMMR) system and a proficient MMR (pMMR) system after MMR status analysis. 45 patients with suspected sporadic dMMR CRC were then separated from MLH1-deficient CRC though BRAF mutation status analysis by IHC. Following the personal and/or family history survey for 1294 patients, as well as germline genetic testing by NGS, 34 patients were diagnosed as LS (8 cases), SLS (13 cases), LLS ( 6 cases), FCCTX (3 cases), and sporadic CRC (4 cases). CONCLUSIONS: Our screening strategy, which consists of clinical and molecular analyses, is expected to improve the screening efficiency and management for the LS and LS mimics.


Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Colorrectales/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/cirugía , Reparación de la Incompatibilidad de ADN , Diagnóstico Diferencial , Femenino , Pruebas Genéticas , Mutación de Línea Germinal , Humanos , Inmunohistoquímica , Masculino , Anamnesis , Inestabilidad de Microsatélites , Persona de Mediana Edad
16.
Pathol Oncol Res ; 27: 1609931, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34975346

RESUMEN

Purpose: Currently, formalin-fixed paraffin-embedded (FFPE) tissue specimens are the conventional material for gene testing for non-small cell lung cancer (NSCLC) patients. In our study, we aimed to develop a quick gene testing procedure using fresh core needle biopsy samples from NSCLC patients. Methods: In total, 77 fresh NSCLC samples obtained from core needle biopsy were evaluated by frozen section examination. If the NSCLC diagnosis and adequate tumor cell counts were confirmed by histopathology, the fresh tissues were used to extract DNA and subsequent gene testing by ARMS-PCR. Meanwhile, the paired FFPE core needle biopsy samples from 30 NSCLC patients also underwent gene testing. Results: In total, 77 fresh samples showed an EGFR mutation rate of 61.0%, higher than the levels in the Asian. Following a comparison of gene testing results with fresh tissues and paired FFPE tissues from the 30 patients, no significant difference in the DNA concentration extracted from fresh tissues and FFPE tissues was found. However, DNA purity was significantly higher in fresh tissues than that in FFPE tissues. Gene testing detected the same gene mutations in 93.3% of cases in fresh tissues and paired FFPE tissues. The gene testing procedure using fresh biopsy samples greatly shortens the waiting time of patients. Conclusion: The multi-gene mutation testing using fresh core needle biopsy samples from NSCLC patients is a reasonable, achievable, and quick approach. Fresh tissues may serve as a potential alternative to FFPE tissues for gene testing in NSCLC patients.


Asunto(s)
Biopsia con Aguja Gruesa , Carcinoma de Pulmón de Células no Pequeñas/genética , Análisis Mutacional de ADN/métodos , Neoplasias Pulmonares/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Formaldehído , Secciones por Congelación , Humanos , Masculino , Persona de Mediana Edad , Adhesión en Parafina , Reacción en Cadena de la Polimerasa/métodos , Fijación del Tejido/métodos
17.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 11): o2940, 2010 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-21589110

RESUMEN

In the title compound, C(22)H(19)ClN(2)O(2)S, the dihedral angle between the phenyl-ene ring and the phthalimide ring system is 4.4 (1)°. There is no hydrogen bonding or π-π stacking in the crystal structure.

18.
World J Gastroenterol ; 26(29): 4327-4342, 2020 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-32848337

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common type of cancer and the fourth leading cause of cancer-related death worldwide. Sarcomatoid HCC, which contains poorly differentiated carcinomatous and sarcomatous components, is a rare histological subtype of HCC that differs from conventional HCC. It is highly aggressive and has a poor prognosis. Its clinicopathological characteristics, surgical outcomes and underlying mechanisms of its highly aggressive nature have not been fully elucidated. AIM: To examine the clinicopathological characteristics and surgical outcomes of sarcomatoid HCC and explore the histogenesis of sarcomatoid HCC. METHODS: In total, 196 patients [41 sarcomatoid HCC and 155 high-grade (Edmondson-Steiner grade III or IV) HCC] who underwent surgical resection between 2007 and 2017 were retrospectively reviewed. The characteristics and surgical outcomes of sarcomatoid HCC were compared with those of patients with high-grade HCC. The histological composition of invasive and metastatic sarcomatoid HCCs was evaluated. RESULTS: Sarcomatoid HCC was more frequently diagnosed at an advanced stage with a larger tumor and higher rates of nonspecific symptom, adjacent organ invasion and lymph node metastasis than high-grade HCC (all P < 0.05). Compared with high-grade HCC patients, sarcomatoid HCC patients are less likely to have typical dynamic imaging features of HCC (44.4% vs 72.7%, P = 0.001) and elevated serum alpha-fetoprotein levels (> 20 ng/mL; 36.6% vs 78.7%, P < 0.001). The sarcomatoid group had a significantly shorter median recurrence-free survival (5.6 mo vs 16.4 mo, log-rank P < 0.0001) and overall survival (10.5 mo vs 48.1 mo, log-rank P < 0.0001) than the high-grade group. After controlling for confounding factors, the sarcomatoid subtype was identified as an independent predictor of poor prognosis. Pathological analyses indicated that invasive and metastatic lesions were mainly composed of carcinomatous components. CONCLUSION: Sarcomatoid HCC was associated with a more advanced stage, atypical dynamic imaging, lower serum alpha-fetoprotein levels and a worse prognosis. The highly aggressive nature of sarcomatoid HCC is perhaps mediated by carcinomatous components.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Hepatectomía/efectos adversos , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento
20.
J Neuropathol Exp Neurol ; 78(8): 685-693, 2019 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-31271432

RESUMEN

Solitary fibrous tumor/hemangiopericytomas (SFT/HPCs) are mesenchymal tumors characterized by "staghorn" blood vessels and collagen deposition. Little is known about SFT/HPCs with papillary architecture. We summarized the clinicopathologic features of 12 patients with papillary SFT/HPCs (8 males and 4 females; median age: 59 years), including 8 previously reported cases. Tumors were present in the meninges (75%, 9/12), adrenal gland (8%, 1/12), orbit (8%, 1/12), or spinal canal (8%, 1/12). Six tumors (50%) had a true papillary architecture with fibrovascular cores and 6 tumors (50%) had a pseudopapillary architecture with vascular cores. Nuclear staining for STAT6 was present in all tested tumors (10/10). RT-PCR indicated NAB2 ex6-STAT6 ex17 fusion in 4 tumors (80%, 4/5) and NAB2 ex4-STAT6 ex2 fusion in 1 tumor (20%, 1/5). Five patients (42%, 5/12), all with tumors in the meninges, developed local recurrence at a median of 61 months after surgery (range: 56-165 months; mean: 88.6 months). These results indicated that the papillary architecture is a morphological form of SFT/HPCs. The recognition of this pattern, with appropriate immunohistochemical analysis and assessment of NAB2-STAT6 fusion, should facilitate the distinction of these rare neoplasms from morphologically similar tumors in the meninges, lung, pleura, and soft tissue.

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