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1.
Tumour Biol ; 42(9): 1010428320957506, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32914709

RESUMO

The development of the multidrug resistance phenotype is one of the major challenges faced in the treatment of cancer. The multidrug resistance phenotype is characterized by cross-resistance to drugs with different chemical structures and mechanisms of action. In this work, we hypothesized that the acquisition of resistance in cancer is accompanied by activation of the epithelial-to-mesenchymal transition process, where the tumor cell acquires a more mobile and invasive phenotype; a fundamental step in tumor progression and in promoting the invasion of other organs and tissues. In addition, it is known that atypical glycosylations are characteristic of tumor cells, being used as biomarkers. We believe that the acquisition of the multidrug resistance phenotype and the activation of epithelial-to-mesenchymal transition provoke alterations in the cell glycophenotype, which can be used as glycomarkers for chemoresistance and epithelial-to-mesenchymal transition processes. Herein, we induced the multidrug resistance phenotype in the PC-3 human prostate adenocarcinoma line through the continuous treatment with the drug paclitaxel. Our results showed that the induced cell multidrug resistance phenotype (1) acquired a mixed profile between epithelial and mesenchymal phenotypes and (2) modified the glycophenotype, showing an increase in the level of sialylation and in the number of branched glycans. Both mechanisms are described as indicators of poor prognosis.


Assuntos
Adenocarcinoma/patologia , Antineoplásicos Fitogênicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Transição Epitelial-Mesenquimal/fisiologia , Paclitaxel/farmacologia , Adenocarcinoma/metabolismo , Resistência a Múltiplos Medicamentos/fisiologia , Glicosilação , Humanos , Células PC-3 , Fenótipo
2.
Prostate ; 80(12): 1012-1023, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32649013

RESUMO

BACKGROUND: Small cell neuroendocrine (NE) carcinomas of the prostate classically lose androgen receptor (AR) expression, may harbor loss of the RB1, TP53, and PTEN tumor suppressor genes, and are associated with a poor prognosis. However usual-type adenocarcinomas may also contain areas of NE differentiation, and in this context the molecular features and biological significance are less certain. METHODS: We examined the molecular phenotype and oncologic outcomes of primary prostate adenocarcinomas with ≥5% NE differentiation (≥5% chromogranin A-positive NE cells in any given tumor spot on tissue microarray) using three independent study sets: a set of tumors with paneth cell-like NE differentiation (n = 26), a retrospective case-cohort of intermediate- and high-risk patients enriched for adverse outcomes (n = 267), and primary tumors from a retrospective series of men with eventual castration-resistant metastatic prostate cancer (CRPC) treated with abiraterone or enzalutamide (n = 55). RESULTS: Benign NE cells expressed significantly lower quantified AR levels compared with paired benign luminal cells (P < .001). Similarly, paneth-like NE carcinoma cells or carcinoma cells expressing chromogranin A expressed significantly lower quantified AR levels than paired non-NE carcinoma cells (P < .001). Quantified ERG protein expression, was also lower in chromogranin A-labeled adenocarcinoma cells compared with unlabeled cells (P < .001) and tumors with NE differentiation showed lower gene expression scores for AR activity compared with those without. Despite evidence of lower AR signaling, adenocarcinomas with NE differentiation did not differ by prevalence of TP53 missense mutations, or PTEN or RB1 loss, compared with those without NE differentiation. Finally, NE differentiation was not associated with time to metastasis in intermediate- and high-risk patients (P = .6 on multivariate analysis), nor with progression-free survival in patients with CRPC treated with abiraterone or enzalutamide (P = .9). CONCLUSION: NE differentiation in usual-type primary prostate adenocarcinoma is a molecularly and clinically distinct form of lineage plasticity from that occurring in small cell NE carcinoma.


Assuntos
Células Neuroendócrinas/patologia , Tumores Neuroendócrinos/patologia , Neoplasias da Próstata/patologia , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Carcinoma de Células Pequenas/genética , Carcinoma de Células Pequenas/metabolismo , Carcinoma de Células Pequenas/patologia , Diferenciação Celular/fisiologia , Estudos de Coortes , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Células Neuroendócrinas/metabolismo , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Receptores Androgênicos/biossíntese , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Proteínas de Ligação a Retinoblastoma/genética , Proteínas de Ligação a Retinoblastoma/metabolismo , Estudos Retrospectivos , Transdução de Sinais , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
3.
Rev Assoc Med Bras (1992) ; 66(5): 590-595, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32638965

RESUMO

OBJECTIVE Thrombopoietin (THPO) is well-known as a megakaryocyte growth and development factor (MGDF) involved in megakaryocyte proliferation and maturation. To explore the biological effects of THPO in gastric adenocarcinoma, we conducted this study. Methods: By accessing the TCGA database, the expression level of THPO was determined in tumor tissues. The association between THPO expression and clinical features, or prognostic significance was described by Cox regression analysis and Kaplan-Meier. The SiRNA method was used to decline the THPO expression; then cell viability, invasion, and migration were detected to verify the effects of the knockdown of THPO. qPCR and western blotting were implemented to examine the expression level of THPO. Results: The expression of THPO was increased in tumor tissue and cells, its high-regulation was associated with a poor prognosis in patients with gastric adenocarcinoma. Cell viability, invasion, and migration were suppressed in AGS with the down-regulation of THPO. Furthermore, on the basis of si-THPO transfection, E-cadherin was promoted while N-cadherin and Vimentin were attenuated. CONCLUSION Our results revealed that THPO may be a potent marker of gastric adenocarcinoma, providing a novel potential screening method for gastric adenocarcinoma.


Assuntos
Adenocarcinoma/diagnóstico , Neoplasias Gástricas/diagnóstico , Trombopoetina/metabolismo , Adenocarcinoma/metabolismo , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica , Prognóstico , Neoplasias Gástricas/metabolismo
4.
Medicine (Baltimore) ; 99(29): e21287, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702921

RESUMO

The potential association between the prognosis of the pancreatic adenocarcinoma (PAAD) and its microenvironment is unclear. This study aims to construct a prognostic index (PI) model of the PAAD microenvironment to predict PAAD patient survival outcomes.The mRNA sequencing and the clinical parameters data were obtained from The Cancer Genome Atlas. Immune and stromal scores were computed using the expression data algorithm to capture infiltration of immune and stromal cells in the PAAD tissue, where patients were categorized as high and low score groups according to these scores. Differentially expressed genes were identified using the R package LIMMA. Univariate and multivariate Cox regression analysis were conducted to select candidate survival-correlated gene signatures from the tumor microenvironment for constructing a model. The Kaplan-Meier method was used to access overall survival of the primary and validation cohorts. The immunological features of the PI model was explored using the Tumor Immune Estimation Resource (TIMER) database. Bioinformatic analyses were conducted based on the DAVID database.A total of 1266 overlapping differentially expressed genes and 49 prognosis-associated genes were identified. A 7-mRNA signature (GBP5, BICC1, SLC7A14, CYSLTR1, P2RY6, VENTX, and RAB39B) was screened for the construction of a PI model (area under the curve = 0.791). In both the primary and validation cohorts, Kaplan Meier analysis revealed that the overall survival of the high-risk group was significantly worse compared to the low-risk group (P < .0001, P = .0028 respectively). The TIMER database described that the 7 signature genes were correlated with immune infiltrating cells and tumor purity. Bioinformatic analyses revealed that these prognosis-associated genes were significantly enriched during inflammation, the defense response, would response, calcium ion transport, and plasma membrane part.A list of the prognosis-correlated genes was generated based on the PAAD microenvironment. A 7-mRNA PI model may be used for predicting the prognosis of PAAD patients.


Assuntos
Adenocarcinoma/metabolismo , Neoplasias Pancreáticas/metabolismo , RNA Mensageiro/metabolismo , RNA Neoplásico/metabolismo , Microambiente Tumoral , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidade , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Transcriptoma
5.
Medicine (Baltimore) ; 99(24): e20554, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541478

RESUMO

Colorectal cancer (CRC) represents a major malignancy globally, with microsatellite instability as its second top molecular mechanism of carcinogenesis. Immunohistochemical (IHC), whose sensitivity and specificity exceed 90%, is used routinely to detect 4 MMR proteins (MLH1, PMS2, MSH2, and MSH6) for screening mismatch repair system defects. We aimed to assess associations of clinicopathologic characteristics with MMR status in resectable CRC patients.Stage I-III CRC cases administered surgical resection in Zhejiang Cancer Hospital in 2013 to 2015 were retrospectively analyzed. MLH1, MSH2, MSH6, and PMS2 protein amounts were evaluated immunohistochemically. Clinicopathological information, including age, sex, tumor location, histological subclass, disease stage, regional lymph node (LN) metastasis, American Joint Committee on Cancer (AJCC) 8th edition stage, and survival data were retrospectively reviewed.A total of 133 CRC cases were assessed, including 74 (55.6%), 45 (33.8%), 55 (41.4%), and 77 (57.9%) not expressing MLH1, MSH2, MSH6, and PMS2, respectively. There were significant associations of MLH1, MSH2, MSH6, and PMS2 proteins with age and sex (P < .05). MLH1, MSH2, and MSH6 (but not PMS2) showed positive associations with primary tumor location (P < .05). Of the 133 patients, 70 and 63 cases were affected on the right and left sides, respectively; significant associations of primary site with age and sex were observed (P < .05). Regarding the MMR status, MLH1, MSH2, and MSH6 protein expression levels were positively associated with primary site (P < .05). Five-year overall survival (OS) rates were 84.2% and 79.2% in left-side and right-side cases, respectively; 5-year disease-free survival (DFS) rates were 74.0% and 69.8%, respectively. Survival had no differences between left- and right-side patients in terms of OS (P = .318) and DFS (P = .481).These data demonstrate that 4 major dMMR proteins are expressed differently in left- and right-side CRCs, and survival is comparable in right- and left-side resectable CRC cases with dMMR.


Assuntos
Adenocarcinoma/genética , Neoplasias Colorretais/genética , Reparo de Erro de Pareamento de DNA , Enzimas Reparadoras do DNA/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento/metabolismo , Proteína 1 Homóloga a MutL/metabolismo , Proteína 2 Homóloga a MutS/metabolismo , Estudos Retrospectivos , Adulto Jovem
6.
J Cancer Res Clin Oncol ; 146(9): 2219-2229, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32507974

RESUMO

PURPOSE: Pancreatic cancer is a lethal form of cancer that can be triggered by prolonged or acute inflammation of the pancreas. Inflammation have been shown to be regulated by a group of key protein molecules known as the inflammasomes. The NLRP3 inflammasome is the most studied inflammasome and have been strongly implicated to regulate cancer cell proliferation. Therefore, this study aimed to examine the regulation of NLRP3 inflammasome under LPS-induced inflammation and its role in modulating cell proliferation in a panel of pancreatic cancer cells. METHODS: The effects of LPS-induced NLRP3 activation in the presence or absence of MCC950, NLRP3-specific inhibitor, was tested on a panel of three pancreatic cancer cell lines (SW1990, PANC1 and Panc10.05). Western blotting, cell viability kits and ELISA kits were used to examine the effects of LPS-induced NLRP3 activation and inhibition by MCC950 on NLRP3 expression, cell viability, caspase-1 activity and cytokine IL-1ß, respectively. RESULTS: LPS-induced inflammation in the presence of ATP activates NLRP3 that subsequently increases pancreatic cancer cell proliferation by increasing caspase-1 activity leading to overall production of IL-1ß. The inhibition of the NLRP3 inflammasome activation via the specific NLRP3 antagonist MCC950 was able to reduce the cell viability of pancreatic cancer cells. However, the efficacy of MCC950 varies between cell types which is most probably due to the difference in ASC expressions which have a different role in inflammasome activation. CONCLUSION: There is a dynamic interaction between inflammasome that regulates inflammasome-mediated inflammation in pancreatic adenocarcinoma cells.


Assuntos
Adenocarcinoma/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Inflamassomos/efeitos dos fármacos , Inflamação/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Sulfonas/farmacologia , Adenocarcinoma/induzido quimicamente , Adenocarcinoma/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Humanos , Inflamassomos/metabolismo , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Neoplasias Pancreáticas/induzido quimicamente , Neoplasias Pancreáticas/metabolismo
7.
Tumour Biol ; 42(6): 1010428320936410, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32586207

RESUMO

Pancreatic ductal adenocarcinoma is the most common and aggressive type of pancreatic cancer, with a 5-year survival rate that is less than 10%. New biomarkers to aid in predicting the prognosis of pancreatic ductal adenocarcinoma patients are needed. Previous proteomic studies have to a great extent focused on finding proteins of value for the diagnosis of pancreatic ductal adenocarcinoma. There is a lack of studies that have profiled the serum or plasma proteome in order to discover candidates for new prognostic biomarkers. In this study, we have used ultra-performance liquid chromatography-ultra-definition mass spectrometry to analyze the serum samples of 21 pancreatic ductal adenocarcinoma patients with short or long survival. Statistical analysis discovered 31 proteins whose expression differed significantly between pancreatic ductal adenocarcinoma patients with short or long survival. Pathway analysis discovered multiple canonical pathways enriched in this data set, with several pathways having roles in inflammation and lipid metabolism. The serum proteins identified here, which include complement components and several enzymes, could be of value as candidates for new noninvasive prognostic markers.


Assuntos
Adenocarcinoma/mortalidade , Biomarcadores Tumorais/metabolismo , Proteínas Sanguíneas/metabolismo , Carcinoma Ductal Pancreático/mortalidade , Neoplasias Pancreáticas/mortalidade , Proteoma/metabolismo , Proteômica/métodos , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Idoso , Biomarcadores Tumorais/análise , Proteínas Sanguíneas/análise , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Projetos Piloto , Prognóstico , Mapas de Interação de Proteínas , Proteoma/análise , Taxa de Sobrevida
8.
J Cancer Res Clin Oncol ; 146(9): 2319-2327, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32592066

RESUMO

PURPOSE: Lymphocyte activation gene-3 (LAG3) is an immunosuppressive checkpoint molecule expressed on T cells. The frequency and distribution of LAG3 expression in oesophageal adenocarcinoma (EAC) is unknown. Aim of the study was the evaluation and distribution of LAG3 on tumour infiltrating lymphocytes (TILs) and correlation with clinico-pathological and molecular data. METHODS: We analysed tumor tissue samples using immunohistochemistry, multi-colour immunofluorescence and mRNA in-situ technology. The analyses were performed on a multi-spot tissue microarray (TMA) with 165 samples, followed by an evaluation on a single-spot TMA with 477 samples. These results were correlated with clinical and molecular tumour data. RESULTS: LAG3 expression on TILs was detectable in 10.5% on the multi-spot TMA and 11.4% on the single-spot TMA. There was a strong correlation between protein expression and mRNA expression (p < 0.001) in TILs. LAG 3 expression was correlated with CD4+ and CD8+ T-cells within the tumor (p < 0.001). LAG3 expression showed an improved overall survival (OS) compared to patients without LAG3 expression (median OS 70.2 vs. 26.9 months; p = 0.046). The effect was even clearer in the group of patients with tumour stages > pT2 (70.2 vs 25.0 months; p = 0.037). CONCLUSION: This is the first description of LAG3 expression on TILs in EAC, underscoring the importance of immunomodulation in EAC. Our data suggest an impact of LAG3 in a relevant subset of EAC. Therapeutic studies investigating the efficacy of LAG3 inhibition in EAC will also provide predictive evidence and relevance of the immunohistochemical determination of LAG3 expression.


Assuntos
Adenocarcinoma/metabolismo , Antígenos CD/metabolismo , Neoplasias Esofágicas/metabolismo , Linfócitos do Interstício Tumoral/metabolismo , RNA Mensageiro/metabolismo , Adenocarcinoma/patologia , Idoso , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Neoplasias Esofágicas/patologia , Feminino , Humanos , Ativação Linfocitária/fisiologia , Linfócitos do Interstício Tumoral/patologia , Masculino , Estadiamento de Neoplasias/métodos
9.
Biol Res ; 53(1): 20, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381120

RESUMO

BACKGROUND: The role of interleukin family in colon cancer remained controversial. The purpose of this study was to investigate the association between interleukin family and colon cancer progression through bioinformatics methods and to validate such association in clinical patients. METHODS: A total of 15 differentially expressed interleukins between the colon cancer tissue and normal colon tissue were evaluated from the Cancer Genome Atlas (TCGA) database with R software and only interleukin-7 (IL-7) was significantly associated with survival. The signaling pathway associated with IL-7 was then investigated using gene enrichment analysis. In addition, subsets of TNM were analyzed in detail and univariate and multivariate COX regression analysis were conducted. Finally, we performed western blotting, immunohistochemistry, cell proliferation and cell apoptosis analysis to examine the expression of IL-7 in patients with intestinal cancer. RESULTS: The study demonstrated that IL-7 could inhibit the progression of colon cancer. In addition, IL-7 was found to be associated with overall survival (OS) and pathological stage. Further analysis of IL-7 expression with clinical data indicated that IL-7 was a key factor in inhibiting colon cancer progression. CONCLUSION: IL-7 was a key factor in inhibiting the progression of colon cancer and was closely related to overall survival.


Assuntos
Adenocarcinoma/metabolismo , Neoplasias do Colo/metabolismo , Interleucina-7/metabolismo , Idoso , Apoptose , Western Blotting , Proliferação de Células , Biologia Computacional , Progressão da Doença , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Masculino , Estadiamento de Neoplasias , Transdução de Sinais
10.
Clin Nucl Med ; 45(7): e309-e310, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32404709

RESUMO

We report the case of a 63-year-old man who underwent MRI and Ga-PSMA-11 PET/CT for biochemical recurrence localization after radical prostatectomy (serum PSA, 0.25 ng/mL) and describe the incidental discovery of a rectal adenocarcinoma. Immunohistochemical analysis showed PSMA staining in the tumor-associated neovasculature, but not in normal vasculature, or tumor cells. After surgical removal, he was treated with salvage radiotherapy to the postoperative prostate bed. This case example has several implications: the findings confirm the expression of PSMA in the tumor-associated neovasculature of a rectal cancer, nonprostate cancers' stroma may represent a potentially relevant target for nuclear theranostics.


Assuntos
Adenocarcinoma/metabolismo , Antígenos de Superfície/metabolismo , Regulação Neoplásica da Expressão Gênica , Glutamato Carboxipeptidase II/metabolismo , Neovascularização Patológica/metabolismo , Medicina Nuclear , Neoplasias Retais/metabolismo , Nanomedicina Teranóstica , Adenocarcinoma/irrigação sanguínea , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/terapia , Humanos , Achados Incidentais , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Prostatectomia , Neoplasias Retais/irrigação sanguínea , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/terapia
12.
PLoS One ; 15(5): e0232934, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32428045

RESUMO

AIMS: Much work has been done to find markers of cancer stem cells (CSCs) that distinguish them from the tumor bulk cells and normal cells. Recent CSC research has applied the induced pluripotent stem cell (iPSC) concept. In this study, we investigated the expression of a panel of iPSC markers in primary colon adenocarcinoma (CA)-derived cell lines. MATERIALS AND METHODS: Expression of iPSC markers by CA-derived primary cell lines was interrogated using immunocytochemistry, western blotting and RT-qPCR. The stem cell function of these cells was then assessed in vitro using differentiation and tumorsphere assays. RESULTS: Expression of iPSC markers OCT4, SOX2, NANOG, KLF4 and c-MYC was more widespread in high-grade CA (HGCA) cell lines than low-grade CA (LGCA) cell lines, as demonstrated by western blotting and RT-qPCR. These cells could be induced to differentiate down the three embryonic lineages. Cells derived from HGCA were more capable of forming tumorspheres than those derived from LGCA. EpCAM sorting revealed that a population enriched for EpCAMHigh cells formed larger tumorspheres than EpCAMLow cells. Pluripotency markers, SSEA4 and TRA-1-60, were co-expressed by a small subpopulation of cells that also co-expressed SOX2 in 75% and OCT4 in 50% of the cell lines. CONCLUSIONS: CA-derived primary cell lines contain tumorsphere-forming cells which express key pluripotency genes and can differentiate down 3 embryonic lineages, suggesting a pluripotent CSC-like phenotype. There appear to be two iPSC-like subpopulations, one with high EpCAM expression which forms larger tumorspheres than another with low EpCAM expression. Furthermore, these cells can be characterized based on iPSC marker expression, as we have previously demonstrated in the original CA tumor tissues.


Assuntos
Adenocarcinoma/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Neoplásicas/metabolismo , Biomarcadores Tumorais/metabolismo , Diferenciação Celular/genética , Linhagem Celular Tumoral , Reprogramação Celular/genética , Colo/citologia , Colo/metabolismo , Neoplasias do Colo/metabolismo , Proteínas de Ligação a DNA/análise , Genes Homeobox , Genes myc , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Fatores de Transcrição Kruppel-Like/análise , Proteína Homeobox Nanog/análise , Fator 3 de Transcrição de Octâmero/análise , Cultura Primária de Células , Fatores de Transcrição SOXB1/análise , Fatores de Transcrição/análise
13.
Clin Nucl Med ; 45(7): e334-e335, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32404713

RESUMO

A 72-year-old man with a family history of prostate cancer and initial diagnosis of favorable intermediate risk prostate cancer via biopsy in 2017 elected for active surveillance. Two years later, he underwent prostate biopsy showing intermediate-risk cT1c Nx Mx lesion with Gleason score 3 + 4 = 7 (5 core positive). Transrectal ultrasound showed a prostate volume 28 mL, and the prostate-specific antigen was 8.1. Patient elected to proceed with combination radiation therapy and androgen deprivation therapy.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Radioisótopos de Flúor , Neoplasias da Próstata/diagnóstico por imagem , Fluoreto de Sódio , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Idoso , Antagonistas de Androgênios/uso terapêutico , Biópsia , Humanos , Masculino , Gradação de Tumores , Tomografia por Emissão de Pósitrons , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Ultrassonografia
14.
Clin Nucl Med ; 45(7): 561-562, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32433166

RESUMO

We present a 78-year-old man with suspicion of prostate cancer due to a PSA of 200 ng/mL, who underwent F-PSMA-1007 (prostate specific membrane antigen) PET/CT for primary staging. Besides heterogeneous uptake to the prostate, an increased PSMA uptake in the cecum was observed, located in the thickened cecal wall with suspicion of a secondary malignancy. Colonoscopic biopsy followed by hemicolectomy confirmed the diagnosis of colon adenocarcinoma. This case demonstrates the importance of bioptic workup of suspicious findings on PSMA PET/CT, which are unlikely to be related to prostate cancer as PSMA ligand uptake is not exclusively prostate cancer specific.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/metabolismo , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/metabolismo , Achados Incidentais , Niacinamida/análogos & derivados , Oligopeptídeos/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Idoso , Transporte Biológico , Humanos , Masculino , Niacinamida/metabolismo
15.
Clin Nucl Med ; 45(7): 555-556, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32453086

RESUMO

Tc-MIBI has long been used to localize hyperfunctioning parathyroid tissue in patients with hyperparathyroidism. This tracer can also concentrate in various neoplastic tissues including prostate adenocarcinoma. We herein report a case with parathyroid hormone-secreting metastatic prostate cancer mimicking an ectopic parathyroid adenoma on the Tc-MIBI scan. We conclude that metastatic prostate cancer should be included as one of the differential diagnoses when interpreting Tc-MIBI scan.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/metabolismo , Hormônio Paratireóideo/metabolismo , Neoplasias das Paratireoides/diagnóstico , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/metabolismo , Tecnécio Tc 99m Sestamibi , Adenocarcinoma/patologia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias da Próstata/patologia , Cintilografia
16.
Surg Today ; 50(10): 1223-1231, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32409870

RESUMO

PURPOSES: Preoperative chemoradiation is a potential treatment option for localized gastric adenocarcinoma (GAC). Currently, the response to chemoradiation cannot be predicted. We analyzed the pretreatment maximum standardized uptake value (SUVmax) and total lesion glycolysis (TLG) on positron emission tomography/computed tomography as potential predictors of the response to chemoradiation. METHODS: We analyzed the SUVmax and TLG data from 59 GAC patients who received preoperative chemoradiation. We used logistic regression models to predict a pathologic complete response (pCR) and Kaplan-Meier curves to determine overall survival among patients with high and low SUVmax or TLG. RESULTS: Twenty-nine patients (49%) had Siewert type III adenocarcinoma and 30 (51%) had tumors located in the lower stomach. Forty-one patients had poorly differentiated GAC, and 26 had signet ring cells. The median SUVmax was 7.3 (0-28.2) and the median TLG was 56.6 (0-1881.5). Patients with signet ring cells had a low pCR rate, as well as a low SUVmax and TLG. In the multivariable logistic regression model, high SUVmax was a predictor of pCR (odds ratio = 11.1, 95% confidence interval = 2.12-50.0, p = 0.004). Overall survival was not associated with the SUVmax (log-rank p = 0.69) or TLG (log-rank p = 0.85) CONCLUSION: A high SUVmax was associated with sensitivity to chemoradiation and pCR in GAC, and signet ring cells seemed to confer resistance.


Assuntos
Adenocarcinoma/metabolismo , Adenocarcinoma/terapia , Carcinoma de Células em Anel de Sinete/metabolismo , Carcinoma de Células em Anel de Sinete/terapia , Quimiorradioterapia Adjuvante , Glicólise , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/terapia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células em Anel de Sinete/diagnóstico por imagem , Carcinoma de Células em Anel de Sinete/patologia , Estudos de Coortes , Análise de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Cuidados Pré-Operatórios , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia
17.
Toxicol Lett ; 331: 92-101, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32446815

RESUMO

Aflatoxin G1 (AFG1) is a member of the carcinogenic aflatoxin family. Our previous studies indicated that oral administration of AFG1 caused tumor necrosis factor (TNF)-α-dependent inflammation that enhanced oxidative DNA damage in alveolar epithelial cells, which may be related to AFG1-induced lung carcinogenesis. High mobility group box-1 (HMGB1) is a nuclear DNA-binding protein; the intracellular and extracellular roles of HMGB1 have been shown to contribute to DNA repair and sterile inflammation. The role of HMGB1 in DNA damage in an aflatoxin-induced lung inflammatory environment was investigated in this study. Upregulation of HMGB1, TLR2, and RAGE was observed in AFG1-induced lung inflamed tissues and adenocarcinoma. Blocking AFG1-induced inflammation by neutralization of TNF-α inhibited the upregulation of HMGB1 in mouse lung tissues, suggesting that AFG1-induced TNF-α-dependent inflammation regulated HMGB1 expression. In the in vitro human pulmonary epithelial cell line model, Beas-2b, AFG1 directly enhanced the cytosolic translocation of HMGB1 and its extracellular secretion. The addition of extracellular soluble HMGB1 protected AFG1-induced DNA damage through the TLR2/NF-κB pathway in Beas-2b cells. In addition, blockade of endogenous HMGB1 by siRNA significantly enhanced AFG1-induced damage. Thus, our findings showed that both extracellularly-released and nuclear and cytosolic HMGB1 could protect the cell from AFG1-induced cell damage in a TNF-α-dependent lung inflammatory environment.


Assuntos
Adenocarcinoma/patologia , Aflatoxinas/toxicidade , Células Epiteliais/efeitos dos fármacos , Proteína HMGB1/metabolismo , Neoplasias Pulmonares/patologia , Pulmão/efeitos dos fármacos , Pneumonia/patologia , Adenocarcinoma/induzido quimicamente , Adenocarcinoma/metabolismo , Animais , Linhagem Celular , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Proteína HMGB1/genética , Humanos , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/metabolismo , Camundongos Endogâmicos BALB C , Pneumonia/induzido quimicamente , Pneumonia/metabolismo , RNA Interferente Pequeno/genética
18.
Medicine (Baltimore) ; 99(16): e19829, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32312004

RESUMO

As a biomarker, neuron-specific enolase (NSE) has been widely recognized in the diagnosis of benign diseases and malignant tumors. This study aimed to investigate the potential diagnostic value of NSE in patients with gastric adenocarcinoma.Serum levels of the NSE were compared between 219 patients with gastric adenocarcinoma and 298 healthy individuals, NSE and clinicopathological parameters were analyzed. Meanwhile, to evaluate the diagnostic capability of NSE, the receiver operating characteristic (ROC), and area under curve (AUC) was calculated.In the present study, the median serum NSE level of the patient group was 20.770 ng/mL, which was higher than that of the control group 15.625 ng/mL (P < .05). Serum NSE level in patients group compared with healthy control was statistically significant (P < .05). Serum NSE level was associated with pathological tumor-node-metastasis (pTNM) staging, lymph node metastasis, and distant metastasis in patients with gastric adenocarcinoma. Besides, the AUC of NSE in gastric adenocarcinoma was 0.742, which was higher than those of the other 3 markers (0.573-0.644). Besides, the AUC of the combined 4 markers was higher than any individual marker (0.778).Serum NSE detecting may have good value for diagnosis of gastric adenocarcinoma. Besides, the combination of NSE, CEA, CA19-9, and CA242 performed even better than any single marker. Thus, the combined detection of the 4 tumor markers may be more useful for the diagnosis of gastric adenocarcinoma.


Assuntos
Adenocarcinoma/metabolismo , Biomarcadores Tumorais/metabolismo , Fosfopiruvato Hidratase/sangue , Neoplasias Gástricas/patologia , Adulto , Idoso , Antígenos Glicosídicos Associados a Tumores/sangue , Antígeno CA-19-9/sangue , Antígeno Carcinoembrionário/sangue , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Sensibilidade e Especificidade
19.
Int. j. morphol ; 38(2): 247-251, abr. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1056430

RESUMO

Nine tumor and various potential biomarkers were measured and combined the information to diagnose disease, all patients accepted fiber bronchoscopy brush liquid based cytologyand histopathology examination in order to reliably detect lung cancer. The samples from 314 Chinese lung cancer patients were obtained and CK5/6, P63, P40, CK7, TTF-1, NapsinA CD56, Syn and CgA were measured with the immunohistochemical SP method and analyzed correlation of the expression of these markers with pathological and clinical features of squamous cell carcinoma, adenocarcinoma, and small cell lung carcinoma. Squamous cell carcinoma, adenocarcinoma and small cell carcinoma were 61 cases, 114 cases and 139 cases,CK5/6 and P63 expression were more frequent in squamous cell carcinoma, with sensitivity and specificity of 77.05 % and 96.44 %, 83.61 % and 88.93 %,and compared with adenocarcinoma and small cell carcinoma difference was statistically significant (P<0.05), The incidences of a positive P40 expression were 100 % in squamous cell carcinoma, with specificity of 98.81 %.CK7, TTF-1 and NapsinA expression were more frequent in adenocarcinoma, with sensitivity and specificity of 85.09 % and 78.69 %, 79.82 % and 93.44 %, 56.14 % and 95.08 %, and compared with squamous cell carcinoma and small cell carcinoma difference was statistically significant (P<0.05). TTF-1, Syn, CgA and CD56 expression were more frequent in adenocarcinoma, with sensitivity and specificity of 86.33 % and 93.44 %, 89.21 % and 98.36 %, 74.10 % and 100 %, 96.40 % and 96.72 %. The combined detection of CK5/6, P63 and P40 were more useful and specific in differentiating squamous cell carcinoma. CK7, TTF-1 and NapsinA were more useful and specific in differentiating lung adenocarcinoma. The impaired CD56, TTF-1, Syn and CgA reflects the progression of small cell lung cancer.


Se midieron tumores y utilizaron nueve biomarcadores potenciales y se analizó la información para diagnosticar la enfermedad. A todos los pacientes se les realizó citología en líquido con broncoscopía de fibra y examen histopatológico para detectar de manera confiable el cáncer pulmonar. Se obtuvieron muestras de 314 pacientes chinos con cáncer de pulmón y CK5 / 6, P63, P40, CK7, TTF-1, Napsina A, CD56, Syn y CgA se midieron a través de histoquímica SP y analizaron la correlación de la expresión de estos marcadores con características patológicas y clínicas de carcinoma de células escamosas, adenocarcinoma y carcinoma de células pequeñas en el cáncer de pulmón. El carcinoma de células escamosas, el adenocarcinoma y el carcinoma de células pequeñas fueron 61 casos, 114 casos y 139 casos, respectivamente, la expresión de CK5 / 6 y P63 fueron más frecuentes en el carcinoma de células escamosas, con una sensibilidad y especificidad del 77,05 % y 96,44 %, 83,61 % y 88,93 %, y en comparación con el adenocarcinoma y el carcinoma de células pequeñas, la diferencia fue estadísticamente significativa (P <0,05). La incidencia de ap la expresión positiva P40 fue del 100 % en el carcinoma de células escamosas, con una especificidad del 98,81 %. La expresión de CK7, TTF-1 y NapsinA fueron más frecuentes en el adenocarcinoma, con una sensibilidad y especificidad del 85,09 % y 78,69 %, 79,82 % y 93,44 %, 56,14 % y 95,08 %, y en comparación con el carcinoma de células escamosas y la diferencia de carcinoma de células pequeñas fue estadísticamente significativa (P <0,05) .TTF-1, Syn, CgA y la expresión de CD56 fueron más frecuentes en adenocarcinoma, con sensibilidad y especificidad de 86.33 % y 93.44 %, 89.21 % y 98.36 %, 74.10 % y 100 %, 96.40 % y 96.72 %. La detección combinada de CK5 / 6, P63 y P40 fue más útil y específica en la diferenciación del carcinoma de células escamosas. CK7, TTF-1 y NapsinA fueron más útiles y específicos para diferenciar el adenocarcinoma de pulmón. El deterioro de CD56, TTF-1, Syn y CgA refleja la progresión del cáncer de pulmón de células pequeñas.


Assuntos
Humanos , Carcinoma/metabolismo , Carcinoma/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Fragmentos de Peptídeos/metabolismo , Fatores de Transcrição/metabolismo , Imuno-Histoquímica , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Biomarcadores Tumorais/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Sensibilidade e Especificidade , Carcinoma de Células Pequenas/metabolismo , Carcinoma de Células Pequenas/patologia , Antígeno CD56/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Queratinas Tipo II/metabolismo , Queratina-7/metabolismo , Fator Nuclear 1 de Tireoide/metabolismo
20.
Cancer Immunol Immunother ; 69(8): 1577-1588, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32306077

RESUMO

HLA-DR, an MHC class II molecule that mediates antigen presentation, is a favourable prognostic indicator in colorectal cancer (CRC). However, the dynamics and location of HLA-DR expression during CRC development are unclear. We aimed to define HLA-DR expression by immunohistochemistry in colorectal epithelium and stromal tissue at different stages of cancer development, assessing non-neoplastic colorectal adenocarcinoma-adjacent tissue, adenomas and carcinoma tissues, and to associate HLA-DR levels with clinical outcomes. Patients with higher than median HLA-DR expression survived at least twice as long as patients with lower expression. This association was significant for HLA-DR staining in the colorectal carcinoma epithelium (n = 152, p = 0.011, HR 1.9, 95% CI 1.15-3.15) and adjacent non-neoplastic epithelium (n = 152, p < 0.001, HR 2.7, 95% CI 1.59-4.66), but not stroma. In stage II cases, however, the prognostic value of HLA-DR expression was significant only in adjacent non-neoplastic tissues, for both epithelium (n = 63, p = 0.015, HR 3.6, 95% CI 1.279-10.25) and stroma (n = 63, p = 0.018, HR 5.07, 95% CI 1.32-19.49). HLA-DR was lower in carcinoma tissue compared to matched adenomas (n = 35), in epithelium (p < 0.01) and stroma (p < 0.001). HLA-DR was further reduced in late-stage carcinoma (n = 101) compared to early stage (n = 105), in epithelium (p < 0.001) and stroma (p < 0.01). HLA-DR expression was lower (p < 0.05) in the adjacent non-neoplastic epithelium of patients with cancer recurrence. We demonstrate a progressive loss of HLA-DR in epithelial and stromal tissue compartments during CRC development and show prognostic ability in carcinoma-adjacent non-neoplastic tissues, highlighting the importance of this molecule in the anti-cancer immune response. These findings may have wider implications for immunotherapeutic interventions.


Assuntos
Adenocarcinoma/patologia , Adenoma/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Antígenos HLA-DR/metabolismo , Recidiva Local de Neoplasia/patologia , Células Estromais/metabolismo , Adenocarcinoma/metabolismo , Adenoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
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