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1.
J Pathol ; 260(2): 165-176, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36815532

RESUMO

Hepatic angiosarcoma (HAS) is an aggressive mesenchymal malignancy that remains underexplored with respect to its etiology and mutational landscapes. To clarify the association between HAS and end-stage renal disease (ESRD), we used nationwide data of the National Health Insurance Research Database (NHIRD) in Taiwan, covering ~99% of the population, from 2001 to 2016. To investigate molecular signatures, we performed whole-exome sequencing (WES) in 27 surgical specimens, including nine ESRD-associated cases. The NHIRD analysis demonstrated that HAS ranked second among all angiosarcomas in Taiwan, with the incidence rates of HAS being 0.08, 2.49, and 5.71 per 100,000 person-years in the general population, chronic kidney disease (CKD), and ESRD patients, respectively. The standardized incidence ratios of HAS in CKD and ESRD patients were 29.99 and 68.77, respectively. In comparison with nonhepatic angiosarcoma, the multivariate regression analysis of our institutional cohort confirmed CKD/ESRD as an independent risk factor for HAS (odds ratio: 9.521, 95% confidence interval: 2.995-30.261, p < 0.001). WES identified a high tumor mutation burden (TMB; median: 8.66 variants per megabase) and dominant A:T-to-T:A transversion in HAS with frequent TP53 (81%) and ATRX (41%) mutations, KDR amplifications/gains (56%), and CDKN2A/B deletions (48%). Notably, ESRD-associated HAS had a significantly higher TMB (17.62 variants per megabase, p = 0.01) and enriched mutational signatures of aristolochic acid exposure (COSMIC SBS22, p < 0.001). In summary, a significant proportion of HAS in Taiwan is associated with ESRD and harbors a distinctive mutational signature, which concomitantly links nephrotoxicity and mutagenesis resulting from exposure to aristolochic acid or related compounds. A high TMB may support the eligibility for immunotherapy in treating ESRD-associated HAS. © 2023 The Pathological Society of Great Britain and Ireland.


Assuntos
Hemangiossarcoma , Falência Renal Crônica , Neoplasias Hepáticas , Insuficiência Renal Crônica , Humanos , Hemangiossarcoma/epidemiologia , Hemangiossarcoma/genética , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/genética , Insuficiência Renal Crônica/complicações , Fatores de Risco , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/genética , Incidência , Mutação
2.
J Neurosci ; 38(5): 1218-1231, 2018 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-29279308

RESUMO

Oxytocin (OXT) receptors (OXTRs) are prominently expressed in hippocampal CA2 and CA3 pyramidal neurons, but little is known about its physiological function. As the functional necessity of hippocampal CA2 for social memory processing, we tested whether CA2 OXTRs may contribute to long-term social recognition memory (SRM) formation. Here, we found that conditional deletion of Oxtr from forebrain (Oxtr-/-) or CA2/CA3a-restricted excitatory neurons in adult male mice impaired the persistence of long-term SRM but had no effect on sociability and preference for social novelty. Conditional deletion of CA2/CA3a Oxtr showed no changes in anxiety-like behavior assessed using the open-field, elevated plus maze and novelty-suppressed feeding tests. Application of a highly selective OXTR agonist [Thr4,Gly7]-OXT to hippocampal slices resulted in an acute and lasting potentiation of excitatory synaptic responses in CA2 pyramidal neurons that relied on N-methyl-d-aspartate receptor activation and calcium/calmodulin-dependent protein kinase II activity. In addition, Oxtr-/- mice displayed a defect in the induction of long-term potentiation, but not long-term depression, at the synapses between the entorhinal cortex and CA2 pyramidal neurons. Furthermore, Oxtr deletion led to a reduced complexity of basal dendritic arbors of CA2 pyramidal neurons, but caused no alteration in the density of apical dendritic spines. Considering that the methodologies we have used to delete Oxtr do not rule out targeting the neighboring CA3a region, these findings suggest that OXTR signaling in the CA2/CA3a is crucial for the persistence of long-term SRM.SIGNIFICANCE STATEMENT Oxytocin receptors (OXTRs) are abundantly expressed in hippocampal CA2 and CA3 regions, but there are little known about their physiological function. Taking advantage of the conditional Oxtr knock-out mice, the present study highlights the importance of OXTR signaling in the induction of long-term potentiation at the synapses between the entorhinal cortex and CA2 pyramidal neurons and the persistence of long-term social recognition memory. Thus, OXTRs in the CA2/CA3a may provide a new target for therapeutic approaches to the treatment of social cognition deficits, which are often observed in patients with neuropsychiatric disorders.


Assuntos
Região CA2 Hipocampal/fisiologia , Região CA3 Hipocampal/fisiologia , Receptores de Ocitocina/genética , Receptores de Ocitocina/fisiologia , Reconhecimento Psicológico/fisiologia , Comportamento Social , Animais , Região CA2 Hipocampal/citologia , Região CA2 Hipocampal/metabolismo , Região CA3 Hipocampal/citologia , Região CA3 Hipocampal/metabolismo , Dendritos/efeitos dos fármacos , Dendritos/ultraestrutura , Córtex Entorrinal/citologia , Córtex Entorrinal/metabolismo , Córtex Entorrinal/fisiologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Deleção de Genes , Potenciação de Longa Duração/genética , Masculino , Memória de Curto Prazo/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/fisiologia , Ocitocina/análogos & derivados , Ocitocina/farmacologia , Células Piramidais/efeitos dos fármacos , Células Piramidais/ultraestrutura , Receptores de N-Metil-D-Aspartato/agonistas , Receptores de Ocitocina/agonistas
3.
Lasers Med Sci ; 32(1): 19-27, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27686889

RESUMO

The aim of this study is to evaluate the treatment outcome and analyze the associated factors of postoperative recurrence in patients who received transoral laser microsurgery for vocal cord leukoplakia. The demographic, histopathological data were retrospectively reviewed and the factors associated with recurrence of vocal leukoplakia after surgery were analyzed statistically. A total of 44 patients, including 36 males and 8 females, with a mean age of 50.4 ± 13.4 years, were enrolled. All the patients received excision of the vocal leukoplakia by carbon dioxide laser (2-4 Watt, ultrapulse mode) under general anesthesia. No patients had malignant transformation after surgery. Postoperative recurrence occurred in 10 patients (22.7 %). Univariate analysis showed that patients who had the habit of cigarette smoking, alcohol drinking, and presence of gastroesophageal reflux disease tended to recur. Among these risk factors, presence of gastroesophageal reflux disease (odds ratio 8.43) was the independent prognostic factor for recurrence using multivariate logistic regression analysis. Carbon dioxide laser excision is effective for treating vocal leukoplakia that is still confined to dysplasia of any degree, with acceptable morbidity. This study suggests that the presence of gastroesophageal reflux disease is the prognostic indicator for postoperative recurrence of vocal leukoplakia. Aggressive treatment of reflux disease for those who have received surgical excision for vocal leukoplakia is indicated.


Assuntos
Terapia a Laser , Leucoplasia/cirurgia , Microcirurgia , Prega Vocal/patologia , Prega Vocal/cirurgia , Adulto , Idoso , Endoscopia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Resultado do Tratamento
5.
Cancers (Basel) ; 15(7)2023 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-37046646

RESUMO

Background: Pancreatic cancer can induce a hypercoagulable state which may lead to clinically apparent thrombosis. However, the effect of anticoagulants remains ambiguous. This study aimed to investigate the potential effect of long-term systemic anticoagulant usage on hospitalization outcomes of patients with pancreatic cancer. Methods: This retrospective study extracted all data from the U.S. Nationwide Inpatient Sample (NIS) database from 2005 to 2018. We included hospitalized adults ≥18 years old with a pancreatic cancer diagnosis identified by International Classification of Diseases ninth revision (ICD-9) and tenth revision (ICD-10) codes. We utilized diagnostic codes ICD9 V58.61 and ICD10 Z79.01, i.e., 'long-term use of anticoagulant', to identify individuals who were on a long-term systemic anticoagulant. The study cohort were then further grouped as being with or without long-term systemic use of an anticoagulant. Propensity score matching was performed to balance the characteristics of the two groups. The risks of life-threatening events, e.g., acute myocardial infarction (AMI), acute heart failure (AHF), sepsis, shock, and acute kidney injury (AKI), in-hospital death, and prolonged length of stay (LOS) in the hospital were compared between the groups by univariable and multivariable logistic regression analyses. Results: The study population consisted of 242,903 hospitalized patients with pancreas cancer, 6.5% (n = 15,719) of whom were on long-term systemic anticoagulants. A multivariable regression analysis showed that long-term systemic anticoagulant use was independently associated with lower odds of sepsis (aOR: 0.81, 95% CI: 0.76-0.85), shock (aOR: 0.59, 95% CI: 0.51-0.68), AKI (aOR: 0.86, 95% CI: 0.81-0.91), in-hospital mortality (aOR: 0.65, 95% CI: 0.60-0.70), and prolonged LOS (aOR: 0.84, 95% CI: 0.80-0.89). Conclusions: Long-term systemic anticoagulant use is associated with better clinical outcomes in terms of decreased risks of some life-threatening events, in-hospital death, and prolonged LOS among hospitalized patients with pancreatic cancer in the U.S.

6.
Artigo em Inglês | MEDLINE | ID: mdl-35228756

RESUMO

AIM: Activating mutations in the epidermal growth factor receptor (EGFR) are predominantly detected in pulmonary adenocarcinoma and have been reported in small cell lung cancer (SCLC) for decades. This retrospective single-center study aimed to determine the frequency and types of EGFR mutations in SCLC in Taiwan. METHODS: This study comprises a consecutive cohort of 161 patients histologically diagnosed with SCLC between January 1992 and August 2014 at the Department of Pathology in Keelung Chang Gung Memorial Hospital, Taiwan. Archived formalin-fixed paraffin-embedded sections from 71 patients were eligible for molecular analysis. EGFR mutation analysis was performed using a fully-automated IdyllaTM EGFR Mutation Test and confirmed a comparable result through Qiagen Therascreen® EGFR RGQ PCR. In addition, EGFR gene copy number was assessed in EGFR-mutated tumors by fluorescence in situ hybridization (FISH). RESULTS: Mutational status of the EGFR gene was successfully analyzed in 63 specimens by both IdyllaTM and Qiagen platforms. Both methods detected L858R point mutation in exon 21 in an 81-year-old female and a 47-year-old male non-smoker. Both tumors show no concurrent EGFR gene amplification. The overall agreement between results obtained with the Idylla™ EGFR Mutation Test and Qiagen Therascreen® EGFR RGQ PCR was 100% Conclusions. Our results showed that EGFR mutation is a rare mutation type in a consecutive series of de novo SCLC. Furthermore, the performance of Idylla™ EGFR Mutation Test and Qiagen Therascreen® EGFR RGQ PCR on archived paraffin sections of limited quantities is available with the high agreement of results.


Assuntos
Receptores ErbB , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Feminino , Humanos , Masculino , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Análise Mutacional de DNA/métodos , Receptores ErbB/genética , Formaldeído , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/diagnóstico , Mutação , Parafina , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/genética
7.
J Clin Neurosci ; 101: 37-46, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35526362

RESUMO

PURPOSE: Solitary type primary intracranial malignant melanoma (PIMM) is extremely rare but fatal. The optimal treatment algorithm according to clinical relevance of symptoms and outcomes is unclear. This series emphasized the prognostic factors of solitary PIMM and established the treatment algorithm for this rare disease. METHODS: Patients with solitary PIMMs were pathologically verified and treated with neurosurgical tumor resection. All solitary PIMMs recruited at our institute received multidisciplinary team care. We analyzed the clinical findings and prognostic factors. RESULTS: The study cohort included 10 patients. PIMMs in solitary type impacted middle-aged populations with male predominance in Taiwan. Most patients (80%) presented a single tumor initially. Six patients had progressed to multiplicity after the initial treatment. Rates of tumor bleeding and leptomeningeal metastasis seeding (LS) are high in solitary PIMMs. Patients who had gross-total resection (GTR) had better survival than those who had incomplete resection, with median overall survival (OS) rates of 170.4 months vs. 5.23 months (p = 0.004). Multiplicity, eloquent area involvement, initial tumor bleeding, LS, hydrocephalus, and Karnofsky Performance Score < 80 at diagnosis were associated with negative outcomes in progression-free survival and OS. Adjuvant radiotherapy for patients who had LS and for those who cannot undergo grossly total tumor removal resulted in a good outcome. CONCLUSIONS: GTR demonstrated better outcomes for solitary PIMM. For recurrent tumors, aggressively repeated surgical resection remained beneficial for selected cases. Adjuvant radiotherapy was a treatment option for LS following operation. We proposed a possible treatment algorithm for solitary PIMM.


Assuntos
Neoplasias Encefálicas , Melanoma , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/cirurgia , Feminino , Humanos , Avaliação de Estado de Karnofsky , Masculino , Melanoma/cirurgia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento
8.
Nat Commun ; 13(1): 3347, 2022 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-35688834

RESUMO

The pathological identification of lymph node (LN) metastasis is demanding and tedious. Although convolutional neural networks (CNNs) possess considerable potential in improving the process, the ultrahigh-resolution of whole slide images hinders the development of a clinically applicable solution. We design an artificial-intelligence-assisted LN assessment workflow to facilitate the routine counting of metastatic LNs. Unlike previous patch-based approaches, our proposed method trains CNNs by using 5-gigapixel images, obviating the need for lesion-level annotations. Trained on 5907 LN images, our algorithm identifies metastatic LNs in gastric cancer with a slide-level area under the receiver operating characteristic curve (AUC) of 0.9936. Clinical experiments reveal that the workflow significantly improves the sensitivity of micrometastasis identification (81.94% to 95.83%, P < .001) and isolated tumor cells (67.95% to 96.15%, P < .001) in a significantly shorter review time (-31.5%, P < .001). Cross-site evaluation indicates that the algorithm is highly robust (AUC = 0.9829).


Assuntos
Algoritmos , Redes Neurais de Computação , Inteligência Artificial , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Metástase Linfática/patologia , Curva ROC
9.
Diagnostics (Basel) ; 11(10)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34679502

RESUMO

Low-grade ovarian serous adenocarcinoma is rarely encountered in the neck region. The diagnosis of this rare malignancy entity in the neck is challenging for both clinicians and pathologists. A 53-year-old female with a chief complaint of a right lower neck mass that had been growing for approximately 2 weeks. The ultrasound-guided fine needle aspiration cytology favored malignancy. The positron emission tomography/computed tomography scan revealed the clustered enlarged lymph nodes with increased radioactivity uptake in the right neck level V, and strong radioactivity uptake was also displayed in the right ovarian regions. Pelvis magnetic resonance imaging displayed right adnexal complex mass supporting the ovarian cancer. An en bloc resection of the right neck lymph node was conducted. Ovarian serous adenocarcinoma with metastasis of lymph nodes in the neck was confirmed through histopathological findings. This study reviews the clinical features of low-grade ovarian serous carcinoma metastasizing to lymph nodes in neck. Although very rare, ovarian cancer with neck metastasis should be considered in the differential diagnosis of a neck mass lesion. The clinical staging would be relatively high due to the quiet entity of the cancer.

10.
Front Pediatr ; 9: 788336, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34926357

RESUMO

Background: Primary spontaneous pneumothorax is potentially life-threatening, and its recurrence is always a serious problem. Pathological examination provides molecular insights into the pathophysiology of primary spontaneous pneumothorax. Objectives: To investigate the association of histopathologic features of primary spontaneous pneumothorax with matrix metalloproteinase expression and their relevance to the recurrence. Methods: A total of 217 tissue section slides in 172 adolescent patients with primary spontaneous pneumothorax were retrospectively reviewed from January 2001 to June 2020. All histopathologic features were recorded and pathologic findings related to ipsilateral recurrence and second surgery were analyzed. Serum levels of matrix metalloproteinases were prospectively measured in 25 primary spontaneous pneumothorax patients receiving surgery and 18 healthy controls. Their relevance to the histopathologic features of primary spontaneous pneumothorax related to its recurrence was also examined. Results: The major presenting histopathologic findings of primary spontaneous pneumothorax were bleb/bulla (98%) followed by fibrosis (68%). Low prevalence of the pathologic findings of granulation tissue and macrophage accumulation were significantly associated with recurrent primary spontaneous pneumothorax, whereas fibrosis was significantly higher in patients receiving more than once surgery. Furthermore, the ratios of matrix metalloproteinase-2/tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 were significantly higher in theses pathological findings as well as multinucleated giant cells and mesothelial cell hyperplasia in comparison with healthy controls. Conclusions: Low prevalence of macrophage accumulation and granulation tissue related to the overexpression of matrix metalloproteinase-2 and-9 activities may contribute to healing impairment and primary spontaneous pneumothorax recurrence.

12.
Biomark Med ; 11(12): 1103-1111, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29053012

RESUMO

AIM: Thioredoxin can reduce the cysteine group of Keap1 which could induce proteasome degradation of Nrf2, PGAM5 and Bcl-xL. Nrf2 regulates redox balance and Bcl-xL is anti-apoptotic and both are important in tumor progression. METHODS: The protein levels of Keap1, thioredoxin, PGAM5 and Bcl-xL in the normal and tumor tissues of 64 subjects with colorectal cancer (CRC) were determined by western blot. RESULTS: The tumor had higher Keap1 but lower PGAM5s and Bcl-xL protein expression than the normal tissue. The ratio of thioredoxin/Keap1 protein level in the normal (OR: 0.12; 95% CI: 0.02-0.83) or tumor tissue (OR: 0.17; 95% CI: 0.03-0.89) was a negative predictor for distant metastasis in CRC. CONCLUSION: Keap1-mediated degradation of PGAM5 and Bcl-xL may be active in CRC. The ratio of thioredoxin/Keap1 protein level may be useful for suggesting distant metastasis in CRC.


Assuntos
Neoplasias Colorretais/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Tiorredoxinas/metabolismo , Idoso , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/metabolismo , Metástase Neoplásica , Fosfoproteínas Fosfatases/metabolismo , Proteína bcl-X/metabolismo
13.
Medicine (Baltimore) ; 96(2): e5582, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28079792

RESUMO

BACKGROUND: The prognostic relevance of topoisomerase II alpha (TOP2A) copy number change remains not well established. This study is aimed to investigate the frequency and pattern of TOP2A aberrations; to correlate TOP2A alterations with human epidermal growth factor receptor 2 (HER2) status and clinicopathological parameters, and further to explore prognostic value of TOP2A and HER2 status in breast cancer in Taiwan. METHODS: We analyzed tissue samples from 311 invasive carcinomas in tissue microarrays for TOP2A and HER2 status by fluorescent in situ hybridization. RESULTS: TOP2A copy number change is an infrequent genetic event (9.8% amplification and 2.7% deletion) and is present in both HER2-amplified and nonamplified tumors. TOP2A amplification is statistically associated with age >50 at diagnosis (P = 0.016) and HER2 amplification (P < 0.001). HER2 amplification, but not TOP2A amplification, is a predictor of unfavorable prognosis (P = 0.002). Univariate and multivariate analysis showed that higher histologic grading, positive nodal involvement, and HER2 positivity were associated with poorer overall survival. Cytogenetically, double minutes-type amplification is the predominant pattern for both genes (HER2: 64% and TOP2A: 93.1%). Homogeneous staining region-type signals of both genes are resistant to RNase digestion, supporting that these were not nuclear accumulation of mRNA transcripts. CONCLUSION: Our results demonstrate the prognostic value of tumor grading, nodal involvement, and HER2 status in Taiwanese breast cancer. TOP2A aberrations are an infrequent event independent of HER2 status, and TOP2A amplification carries no prognostic value. The predictive value of TOP2A aberrations in patients of breast cancer taking athracycline-containing treatment in Taiwan remains to be determined in prospectively well-designed clinical trials.


Assuntos
Antígenos de Neoplasias/genética , Neoplasias da Mama/genética , Carcinoma/genética , Variações do Número de Cópias de DNA , DNA Topoisomerases Tipo II/genética , Proteínas de Ligação a DNA/genética , Genes erbB-2 , Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinoma/mortalidade , Carcinoma/patologia , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Pessoa de Meia-Idade , Proteínas de Ligação a Poli-ADP-Ribose , Análise de Sobrevida , Taiwan/epidemiologia
14.
Dis Markers ; 2016: 8143465, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27999449

RESUMO

Heme oxygenase 1 (Hmox1) plays an important role in the growth and spread of tumor, and its expression is regulated positively by Nrf2 [nuclear factor (erythroid-derived 2)-like 2; NFE2L2] and negatively by kelch-like ECH-associated protein 1 (Keap1) and by BTB and CNC homology 1 (Bach1). Both Hmox1 and Nrf2 contribute to distant metastasis of cancer. The mRNA levels of Hmox1, Nrf2, Keap1, and Bach1 in the tumor and normal tissues of 84 subjects with colorectal cancer (CRC) were determined by real-time polymerase chain reaction. The tumor had lower Hmox1 but higher Bach1 mRNA levels than the normal tissue. The correlations of Hmox1 with components of the Nrf2 pathway were not significant in the tumor tissue of CRC subjects with distant metastasis. The ratio of Hmox1/Nrf2 mRNA level (by percentage) in the tumor tissue was lower in the subjects with distant metastasis (97.4% (84.4-111.1%)) than in those without (101.0% (92.7-136.5%)) and was a predictor for distant metastasis in CRC (odds ratio: 0.83; 95% confidence interval: 0.68-0.97) along with serum carcinoembryonic antigen (1.0027, 1.006-1.064). The mRNA level of Hmox1 in the tumor tissue of CRC is not correlated with that of the Nrf2 pathway molecules, and its ratio to the Nrf2 level may be useful for suggesting distant metastasis in CRC.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/metabolismo , Heme Oxigenase-1/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Idoso , Idoso de 80 Anos ou mais , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Proteínas de Grupos de Complementação da Anemia de Fanconi/genética , Proteínas de Grupos de Complementação da Anemia de Fanconi/metabolismo , Feminino , Heme Oxigenase-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Fator 2 Relacionado a NF-E2/genética , Metástase Neoplásica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
15.
Medicine (Baltimore) ; 93(29): e349, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25546690

RESUMO

Toll-like receptor (TLR) 9 plays a role in intestinal inflammation that, in turn, is related to the tumorigenesis of colorectal cancer. Nuclear factor κB (NFκB), and interferon regulatory factor (IRF) 5 and IRF7 can be activated by TLR9 and induce the production of proinflammatory cytokines and type I interferon, respectively. This study investigated the mRNA expressions of TLR9 and its downstream signaling molecules in both the tumor and the normal tissues of colorectal cancer. Eighty-four subjects with colorectal cancer were consecutively recruited at a community-based hospital, and the mRNA expression of TLR9, NFκB, IRF5, IRF7, interleukin 6 (IL6), and interferon α/ß/ω receptor 1 (IFNAR1) in the tumor and normal tissue were determined by real-time reverse transcription polymerase chain reaction using TaqMan FAM-labeled MGB probes (Life Technologies, Carlsbad, CA). The tumor had higher percentages of detection of TLR9, IFNAR1, and IL6 mRNA expressions than normal tissue. The absence of detectable TLR9 mRNA expression was associated with an absence of significance in the correlation between IL6 and NFκB or IRF5, but not that between IRF7 and IFNAR1 in both the tumor and the normal tissues. An absence of detectable IFNAR1 mRNA expression in the tumor (hazard ratio: 3.77; 95% confidence interval: 1.22-11.60) and advanced stage (stages III and IV, 7.86; 1.76-35.40) were significant predictors for overall survival. IFNAR1 is a predictor for overall survival and mRNA expression is correlated to IRF7, but not TLR9 in colorectal cancer. The results cast doubt on the usefulness of TLR9 agonist in treating colorectal cancer.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Proteínas de Neoplasias/genética , RNA Mensageiro/metabolismo , Receptor de Interferon alfa e beta/genética , Fatores Etários , Idoso , Neoplasias Colorretais/patologia , Feminino , Humanos , Fator Regulador 7 de Interferon/genética , Fatores Reguladores de Interferon/genética , Interleucina-6/genética , Masculino , Subunidade p50 de NF-kappa B/genética , Proteínas de Neoplasias/metabolismo , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase em Tempo Real , Receptor de Interferon alfa e beta/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Receptor Toll-Like 9/genética
16.
Virchows Arch ; 464(6): 689-99, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24756215

RESUMO

Immunohistochemical expression of ERα, encoded by the ESR1 (estrogen receptor 1) gene located at 6q25.1, is the most important determinant of responsiveness to endocrine therapy in breast cancer. The prevalence and significance of ESR1 amplification in breast cancer remain controversial. We set out to assess ESR1 status and its relevance in breast cancer in Taiwan. We tested tissue samples from 311 invasive carcinomas in a tissue microarray for ESR1 status by fluorescent in situ hybridization (FISH) and chromogenic in situ hybridization (CISH). In order to examine its association with ERα and ESR1 status, HER2 status was determined by FISH. Of the carcinomas, 58.8 % (183/311) was ERα positive. None of the carcinomas showed amplification of ESR1 by either method, whereas 24.1 % (75/311) of the carcinomas harbored HER2 amplification. Of the carcinomas, 9.6 % (26/301) showed ESR1 gain (1.3 ≤ ratio ESR1/chromosome 6 < 2) by FISH and 10 % (24/299) by CISH. FISH and CISH results showed a good correlation (κ-coefficient = 0.786). ESR1 gain by FISH and CISH was significantly associated with high-grade (P = 0.0294 and 0.0417, respectively) but not with ERα expression, HER2 status, or overall survival. ERα positivity was significantly associated with better overall survival (P = 0.039). HER2 amplification was significantly related with poor overall survival (P = 0.002). Our data confirm that in breast cancer, HER2 amplification is a frequent genetic aberration and a negative prognostic factor, and show that ESR1 amplification is not a key genetic abnormality in the tumorigenesis of breast cancer in Taiwan.


Assuntos
Neoplasias da Mama/genética , Carcinoma/genética , Receptor alfa de Estrogênio/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinoma/mortalidade , Carcinoma/patologia , Feminino , Amplificação de Genes , Genes erbB-2/genética , Humanos , Imuno-Histoquímica , Hibridização In Situ , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Taiwan , Análise Serial de Tecidos
17.
PLoS One ; 9(8): e105676, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25148045

RESUMO

Stem cell markers are upregulated in various cancers and have potential as prognostic indicators. The objective of this study was to determine the expression of three stem cell markers, aldehyde dehydrogenase 1 (ALDH-1), B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1), and Nanog, in esophageal squamous cell carcinoma (ESCC) tissues. Immunohistochemistry was used to measure the expression of ALDH-1, Bmi-1, and Nanog in ESCC tissues from 41 patients who received pre-operative chemoradiation. We evaluated the relationship between expression of these markers, and clinicopathological features, tumor regression grade (TRG), and 5-year overall survival (OS). There were no significant associations of ALDH-1 or Bmi-1 expression with age, gender, clinical stage, and treatments (p>0.05). However, patients with Nanog-positive tumors were significantly older than those whose tumors were Nanog-negative (p = 0.033). TRG after treatment was significantly associated with expression of ALDH-1 (p = 0.001), Bmi-1 (p = 0.004), and Nanog (p<0.001). Although OS was significantly better in patients with low TRGs (p = 0.001), there were no significant correlations between ALDH-1, Bmi-1, or Nanog with OS. Expression of ALDH-1, Bmi-1, and Nanog correlated with TRG, but not OS. Further large studies are necessary to fully elucidate the prognostic value of these stem cell markers for ESCC patients.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas , Neoplasias Esofágicas , Proteínas de Homeodomínio/metabolismo , Isoenzimas/metabolismo , Proteínas de Neoplasias/metabolismo , Células-Tronco Neoplásicas , Complexo Repressor Polycomb 1/metabolismo , Retinal Desidrogenase/metabolismo , Adulto , Idoso , Família Aldeído Desidrogenase 1 , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Intervalo Livre de Doença , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína Homeobox Nanog , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Estudos Retrospectivos , Taxa de Sobrevida
18.
Oral Oncol ; 49(1): 86-92, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22840786

RESUMO

PURPOSE: To investigate the intraepithelial microvascular morphology of oral squamous cell carcinoma (OSCC) by using narrow-band imaging (NBI) and analyze whether the intraepithelial papillary capillary loop (IPCL) patterns correlate with infiltration depth and disease severity in OSCC. METHODS: The clinicopathologic data, morphology of vascular architecture as observed by NBI, and histopathology of patients with OSCC were retrospectively reviewed and analyzed. RESULTS: A total of 80 patients, including 73 males and 7 females with an average age of 54.18±12.23 years, were enrolled. Three patterns of intraepithelial microvasculature were revealed by NBI and differences in these three patterns were significant with regard to pathologic T-classification (p<0.0001), N-classification (p=0.00022), TNM stage (p<0.0001), lymphovascular invasion (p<0.0001), perineural invasion (p=0.000299), depth of tumor infiltration (p<0.0001), and tumor differentiation (p<0.0001). A cut-off point of tumor infiltration of 10.012 mm was best predicted for the destructive pattern of IPCL (sensitivity=100%, specificity=90.0%). CONCLUSIONS: Three different patterns of IPCL, showing step-wise increased severity according to pathologic parameters, were observed by NBI in cases of OSCC. The pattern indicating IPCL destruction with angiogenesis was associated with more advanced disease stage.


Assuntos
Carcinoma de Células Escamosas/irrigação sanguínea , Microvasos/ultraestrutura , Neoplasias Bucais/irrigação sanguínea , Imagem de Banda Estreita/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Capilares/ultraestrutura , Carcinoma de Células Escamosas/classificação , Carcinoma de Células Escamosas/patologia , Epitélio/irrigação sanguínea , Epitélio/patologia , Feminino , Seguimentos , Humanos , Linfonodos/irrigação sanguínea , Linfonodos/patologia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Neovascularização Patológica/patologia , Estudos Retrospectivos , Sensibilidade e Especificidade
19.
Oncol Lett ; 4(3): 517-520, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22970049

RESUMO

Lung cancer is one of the leading causes of cancer-related mortality worldwide. Gastrointestinal metastasis from primary lung cancer is rare. Only a few reports have been published and the majority of described metastatic sites involved the small intestine. In the present study, we report the first case of primary lung adenocarcinoma with both gastric and colonic metastases. We also review the published literature of primary lung cancer with gastrointestinal metastasis.

20.
Diagn Pathol ; 6: 96, 2011 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-21970525

RESUMO

The kidney is a relatively infrequent site for solitary fibrous tumor (SFT). Among the previously reported cases, only two cases of malignant renal SFT developing via dedifferentiation from a pre-existing benign SFT have been reported. Here we reported a case of de novo malignant renal SFT clinically diagnosed as renal cell carcinoma in a 50-year-old woman. The tumor was circumscribed but unencapsulated and showed obvious hemorrhagic necrosis. Microscopically, the tumor was composed of patternless sheets of alternating hypercellular and hypocellular areas of spindle cells displaying mild to moderate nuclear atypia, frequent mitoses up to 8 per 10 high power fields, and a 20% Ki-67 proliferative index. Immunohistochemical studies revealed reactivity for CD34, CD99 and vimentin, with no staining for all other markers, confirming the diagnosis of SFT. No areas of dedifferentiation were seen after extensive sampling. Based on the pathologic and immunohistochemical features, a diagnosis of de novo malignant renal SFT was warranted. Our report expands the spectrum of malignant progression in renal SFTs. Even though this patient has been disease-free for 30 months, long-term follow-up is still mandatory.


Assuntos
Neoplasias Renais/patologia , Tumores Fibrosos Solitários/patologia , Biomarcadores Tumorais/análise , Carcinoma de Células Renais/patologia , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Renais/metabolismo , Neoplasias Renais/cirurgia , Pessoa de Meia-Idade , Nefrectomia , Tumores Fibrosos Solitários/metabolismo , Tumores Fibrosos Solitários/cirurgia
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