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1.
Int J Med Sci ; 16(4): 583-592, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31171910

RESUMO

Aims: Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) are members of the glycosylphosphatidylinositol (GPI)-linked immunoglobulin (Ig) superfamily and take part in regulation of cell adhesion, tumor suppression and angiogenesis. Overexpression of CEACAM 1, 5 and 6 is widely described in several gastrointestinal epithelial tumors. The aim of study was to evaluate the expression of CEACAM 1, CEACAM 5 and CEACAM 6 in the most common precursor lesions of pancreatic ductal adenocarcinoma -pancreatic intraepithelial neoplasia (PanIN). Methods and results: The study group consisted of 32 patients treated for chronic pancreatitis and 38 patients with pancreatic ductal adenocarcinoma who also had pancreatic intraepithelial neoplasia. The expression of CEACAM was performed by immunohistochemical method and evaluated using 3-point scale: 0 - lack of positive reaction in pancreatic intraepithelial neoplasia, 1 (weak and moderate) - reaction present in 1-30% epithelial cells in PanIN and 2 (strong) - reaction present in >30% epithelial cells in PanIN. Expression of CEACAM 1, 5 and 6 increased with increasing degree of advancement of PanIN. Differences in expression of CEACAM 1, 5 and 6 between normal pancreatic ducts and different degrees of PanIN were statistically significant (p<0.001). We observed relationship between CEACAM1 expression and localization of PanIN in different parts of the pancreas. Conclusions: CEACAM 1, CEACAM 5 and CEACAM 6 expression appears to be an early event in pancreatic carcinogenesis. Moreover, expression of CEACAM 1, 5 and 6 may represent a useful biomarker that may aid in the identification of precancerous lesions in the pancreas.


Assuntos
Adenocarcinoma/genética , Antígenos CD/genética , Antígeno Carcinoembrionário/genética , Carcinoma Ductal Pancreático/genética , Moléculas de Adesão Celular/genética , Adenocarcinoma/complicações , Adenocarcinoma/patologia , Idoso , Biomarcadores Tumorais/genética , Carcinogênese/genética , Carcinoma in Situ/complicações , Carcinoma in Situ/genética , Carcinoma in Situ/patologia , Carcinoma Ductal Pancreático/patologia , Feminino , Proteínas Ligadas por GPI/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/metabolismo , Pâncreas/patologia , Pancreatite Crônica/complicações , Pancreatite Crônica/genética , Pancreatite Crônica/patologia
2.
Medicine (Baltimore) ; 98(19): e15629, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31083261

RESUMO

OBJECTIVE: To determine the effects and mechanism of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1, CC1)-mediated regulation of the Coxsackie and Adenovirus Receptor (CAR) after Coxsackievirus B3 (CVB3) infection. METHODS: A mouse CC1 overexpression recombinant virus was constructed, followed by insertion of a pLVX-CEACAM 1-zsgreen-puro (rLV-CEACAM 1) plasmid into the recombinant retrovirus. Cardiac myocytes were assigned into different groups according to various treatments. The apoptosis rate and cell activity in each group were observed. Further, CAR expression and SYK, IL-1ß, and p-SYK levels were measured. RESULTS: The recombinant retrovirus titer was measured as 1.5 × 10 TUs/ml. The apoptosis rate of cardiac myocytes in the CC1 overexpression plus CVB3 group was significantly elevated, and the relative expression of the CAR gene was the highest in the CC1 overexpression plus CVB3 group. TNF-α and IL-1ß levels increased due to CC1 overexpression and further increased after CVB3 infection. CAR protein expression also changed along with the levels of CC1, SYK, and TNF-α after infection. CONCLUSION: CC1 may promote CAR expression after CVB3 infection and regulate CAR protein expression by activating the CC1-SYK-TNF-α signaling axis during the infection process.


Assuntos
Antígeno Carcinoembrionário/metabolismo , Proteína de Membrana Semelhante a Receptor de Coxsackie e Adenovirus/metabolismo , Infecções por Coxsackievirus/metabolismo , Cardiopatias/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Animais , Apoptose/fisiologia , Antígeno Carcinoembrionário/genética , Infecções por Coxsackievirus/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Cardiopatias/etiologia , Cardiopatias/patologia , Interleucina-1beta/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Células Musculares/metabolismo , Células Musculares/patologia , Organismos Livres de Patógenos Específicos , Quinase Syk/antagonistas & inibidores , Quinase Syk/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
3.
Diagn Cytopathol ; 47(7): 670-674, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30821430

RESUMO

BACKGROUND: Intraperitoneal malignant cells detection in patients with gastric cancer is associated with a significant decrease in overall survival. The overall accuracy of cytological examination of peritoneal lavages, however, is quite low, and intraperitoneal recurrence has been observed even in patients with negative cytology. Immunocytochemistry and molecular techniques have been investigated to improve high-risk patients' identification with variable results. The aim of this study was to compare the performance of different laboratory methods applied to peritoneal washing, to improve the cytological identification of malignant cells. METHODS: We prospectively evaluated 21 patients who underwent surgery and peritoneal lavage for gastric cancer. Among them, 18 had negative cytology and three were positive for malignant cells. For each patient, immunohistochemistry with BerEP4 antibody was performed on seriate sections of cellblock preparation at different levels, using the method reported for sentinel nodes in other types of cancer. Paired frozen quotes of washing fluids were evaluated by qRT-PCR with primer for mRNA of Ceacam5. RESULTS: In 4 of 18 patients with previous negative routine cytology, isolated neoplastic cells in seriate sections of the cellblock inclusion have been found. Results showed to be coherent with molecular analysis for CEA mRNA. CONCLUSION: The sensitivity and specificity of peritoneal washing analyses should be notably improved by immunohistochemistry applied to multilevel cellblock sectioning. The method is less expensive and more widely applicable than molecular analysis, in each laboratory setting. This approach allows detection of minimum peritoneal seeding in patients with gastric cancer.


Assuntos
Líquido Ascítico/patologia , Biomarcadores Tumorais/metabolismo , Lavagem Peritoneal/métodos , Neoplasias Gástricas/patologia , Líquido Ascítico/metabolismo , Biomarcadores Tumorais/genética , Antígeno Carcinoembrionário/genética , Antígeno Carcinoembrionário/metabolismo , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Humanos , Lavagem Peritoneal/normas , Sensibilidade e Especificidade , Neoplasias Gástricas/metabolismo
4.
Scand J Clin Lab Invest ; 79(1-2): 71-74, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30727773

RESUMO

Tumor markers are noninvasive diagnostic tools for cancer. Their abnormal expression often occurs earlier than clinical symptoms or other detection signals. Appropriate reference intervals (RIs) of tumor markers are important for health evaluation, cancer diagnosis, therapy monitoring and prognosis assessment. In this study, we aimed to establish the RIs of cancer antigen 125 (CA125), CA15-3, CA19-9, CA72-4, alpha fetoprotein (AFP), carcino-embryonic antigen (CEA), neuron-specific enolase (NSE) and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) in apparently healthy Henan population. A total of 1705 apparently healthy participants (21-89 years) were recruited from five representative geographical regions in Henan province. Nonparametric 95th percentile intervals were used to define the RIs of CA125, CA15-3, CA19-9, CA72-4, AFP, CEA, NSE and CYFRA21-1. The test results of CA125, CA15-3, CA19-9, CA72-4, AFP, CEA, NSE and CYFRA21-1 can traceable to reference measurement procedures. The age- and gender-specific RIs of the tumor markers were established. We established age- and gender-specific RIs for CA125, CA15-3, CA19-9, CA72-4, AFP, CEA, NSE and CYFRA21-1. The newly established RIs should be more suitable for Henan population. It will be valuable for clinicians to make a medical diagnosis, therapeutic management decision and other physiological assessment.


Assuntos
Antígenos de Neoplasias/genética , Antígenos Glicosídicos Associados a Tumores/genética , Biomarcadores Tumorais/genética , Antígeno Ca-125/genética , Antígeno CA-19-9/genética , Antígeno Carcinoembrionário/genética , Queratina-19/genética , Mucina-1/genética , Fosfopiruvato Hidratase/genética , alfa-Fetoproteínas/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/sangue , Antígenos Glicosídicos Associados a Tumores/sangue , Biomarcadores Tumorais/sangue , Antígeno Ca-125/sangue , Antígeno CA-19-9/sangue , Antígeno Carcinoembrionário/sangue , China , Feminino , Voluntários Saudáveis , Humanos , Queratina-19/sangue , Masculino , Pessoa de Meia-Idade , Mucina-1/sangue , Fosfopiruvato Hidratase/sangue , Gravidez , Valores de Referência , Fatores Sexuais , alfa-Fetoproteínas/metabolismo
5.
Metabolism ; 93: 33-43, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30664851

RESUMO

BACKGROUND: CEACAM1 regulates insulin sensitivity by promoting insulin clearance. Accordingly, global C57BL/6J.Cc1-/- null mice display hyperinsulinemia due to impaired insulin clearance at 2 months of age, followed by insulin resistance, steatohepatitis, visceral obesity and leptin resistance at 6 months. The study aimed at investigating the primary role of hepatic CEACAM1 in insulin and lipid homeostasis independently of its metabolic effect in extra-hepatic tissues. METHODS: Liver-specific C57BL/6J.AlbCre+Cc1fl/fl mice were generated and their metabolic phenotype was characterized by comparison to that of their littermate controls at 2-9 months of age, using hyperinsulinemic-euglycemic clamp analysis and indirect calorimetry. The effect of hyperphagia on insulin resistance was assessed by pair-feeding experiments. RESULTS: Liver-specific AlbCre+Cc1fl/fl mutants exhibited impaired insulin clearance and hyperinsulinemia at 2 months, followed by hepatic insulin resistance (assessed by hyperinsulinemic-euglycemic clamp analysis) and steatohepatitis at ~ 7 months of age, at which point visceral obesity and hyperphagia developed, in parallel to hyperleptinemia and blunted hypothalamic STAT3 phosphorylation in response to an intraperitoneal injection of leptin. Hyperinsulinemia caused hypothalamic insulin resistance, followed by increased fatty acid synthase activity, which together with defective hypothalamic leptin signaling contributed to hyperphagia and reduced physical activity. Pair-feeding experiment showed that hyperphagia caused systemic insulin resistance, including blunted insulin signaling in white adipose tissue and lipolysis, at 8-9 months of age. CONCLUSION: AlbCre+Cc1fl/fl mutants provide an in vivo demonstration of the key role of impaired hepatic insulin clearance and hyperinsulinemia in the pathogenesis of secondary hepatic insulin resistance independently of lipolysis. They also reveal an important role for the liver-hypothalamic axis in the regulation of energy balance and subsequently, systemic insulin sensitivity.


Assuntos
Antígeno Carcinoembrionário/genética , Hiperinsulinismo/complicações , Resistência à Insulina , Fígado/metabolismo , Animais , Técnica Clamp de Glucose , Hiperfagia/complicações , Hipotálamo/metabolismo , Lipólise , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
6.
BMC Immunol ; 20(1): 7, 2019 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-30674283

RESUMO

BACKGROUND: Systemic inflammation and the fever response to pathogens are coordinately regulated by IL-6 and IL-1ß. We previously showed that CEACAM1 regulates the LPS driven expression of IL-1ß in murine neutrophils through its ITIM receptor. RESULTS: We now show that the prompt secretion of IL-6 in response to LPS is regulated by CEACAM1 expression on bone marrow monocytes. Ceacam1-/- mice over-produce IL-6 in response to an i.p. LPS challenge, resulting in prolonged surface temperature depression and overt diarrhea compared to their wild type counterparts. Intraperitoneal injection of a 64Cu-labeled LPS, PET imaging agent shows confined localization to the peritoneal cavity, and fluorescent labeled LPS is taken up by myeloid splenocytes and muscle endothelial cells. While bone marrow monocytes and their progenitors (CD11b+Ly6G-) express IL-6 in the early response (< 2 h) to LPS in vitro, these cells are not detected in the bone marrow after in vivo LPS treatment perhaps due to their rapid and complete mobilization to the periphery. Notably, tissue macrophages are not involved in the early IL-6 response to LPS. In contrast to human monocytes, TLR4 is not expressed on murine bone marrow monocytes. Instead, the alternative LPS receptor RP105 is expressed and recruits MD1, CD14, Src, VAV1 and ß-actin in response to LPS. CEACAM1 negatively regulates RP105 signaling in monocytes by recruitment of SHP-1, resulting in the sequestration of pVAV1 and ß-actin from RP105. CONCLUSION: This novel pathway and regulation of IL-6 signaling by CEACAM1 defines a novel role for monocytes in the fever response of mice to LPS.


Assuntos
Antígenos CD/metabolismo , Antígeno Carcinoembrionário/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/imunologia , Monócitos/imunologia , Monócitos/metabolismo , Animais , Antígeno Carcinoembrionário/genética , Imunofluorescência , Expressão Gênica , Técnicas de Inativação de Genes , Interleucina-6/genética , Receptores de Lipopolissacarídeos/metabolismo , Fígado/citologia , Fígado/imunologia , Fígado/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Modelos Biológicos , Células Mieloides/imunologia , Células Mieloides/metabolismo , Especificidade de Órgãos/genética , Baço/citologia , Baço/imunologia , Baço/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
7.
Breast Cancer Res Treat ; 174(2): 375-385, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30535933

RESUMO

AIM: To investigate the clinical and prognostic significance of circulated tumor cells (CTC) marked by cytokeratin 19 coding gene KRT19 mRNA and carcinoembryonic antigen coding gene CEACAM5 mRNA in preoperative peripheral blood of breast cancer patients and provide molecular markers for breast cancer metastasis risk. METHODS: The mRNA levels of KRT19 and CEACAM5 in preoperative peripheral blood of breast cancer patients without (n = 603) and with (n = 76) distant metastases at the time of initial diagnosis were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The relationship between CTCKRT19, CTCCEACAM5 and clinicopathological features, local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), or overall survival (OS) was statistically analyzed. RESULTS: In different pathological stages of breast cancer, the rates of CTCKRT19-pos and CTCCEACAM5-pos increased with the increase of the stages (P = 0.077 and P = 0.004). Preoperative CTCKRT19-pos in breast cancer patients was closely related to the lymph node metastasis statues (P < 0.0001), and had no significant correlation with other clinicopathological features. There was no significant correlation between CTCCEACAM5 and the clinicopathological features. Patients with high levels of CTC double-marked by KRT19 and CEACAM5 mRNA had shorter DMFS (P < 0.0001) and OS (P = 0.016) for patients with breast cancer. The 7-year DMFS rates for the low-, intermediate-, and high-risk groups were 90.7%, 67.5%, and 59.1%, respectively (P < 0.0001). The prognosis of patients with decreased KRT19 and CEACAM5 mRNA after treatment is better than that of patients who have not decreased, and the combination of the two indicators is better than the single one for predicting PFS (P = 0.002 compare with P = 0.036 or P = 0.047). CONCLUSION: Double-marked CTC by KRT19 and CEACAM5 mRNA is a prognostic index of breast cancer patients before surgery and after chemotherapy. Single-marked CTC by KRT19 mRNA indicates lymph node statues of preoperative patients. Therefore, the RT-qPCR-based molecular diagnosis of CTC could be used for prognostic prediction of breast cancer patients and guiding clinical treatment.


Assuntos
Neoplasias da Mama/patologia , Antígeno Carcinoembrionário/genética , Queratina-19/genética , Células Neoplásicas Circulantes/patologia , Regulação para Cima , Adulto , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Feminino , Proteínas Ligadas por GPI/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Células Neoplásicas Circulantes/química , Prognóstico , Análise de Sobrevida
8.
Proc Natl Acad Sci U S A ; 115(19): E4473-E4482, 2018 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-29686080

RESUMO

Prostate cancer is a heterogeneous disease composed of divergent molecular and histologic subtypes, including prostate adenocarcinoma (PrAd) and neuroendocrine prostate cancer (NEPC). While PrAd is the major histology in prostate cancer, NEPC can evolve from PrAd as a mechanism of treatment resistance that involves a transition from an epithelial to a neurosecretory cancer phenotype. Cell surface markers are often associated with specific cell lineages and differentiation states in normal development and cancer. Here, we show that PrAd and NEPC can be broadly discriminated by cell-surface profiles based on the analysis of prostate cancer gene expression datasets. To overcome a dependence on predictions of human cell-surface genes and an assumed correlation between mRNA levels and protein expression, we integrated transcriptomic and cell-surface proteomic data generated from a panel of prostate cancer cell lines to nominate cell-surface markers associated with these cancer subtypes. FXYD3 and CEACAM5 were validated as cell-surface antigens enriched in PrAd and NEPC, respectively. Given the lack of effective treatments for NEPC, CEACAM5 appeared to be a promising target for cell-based immunotherapy. As a proof of concept, engineered chimeric antigen receptor T cells targeting CEACAM5 induced antigen-specific cytotoxicity in NEPC cell lines. Our findings demonstrate that the surfaceomes of PrAd and NEPC reflect unique cancer differentiation states and broadly represent vulnerabilities amenable to therapeutic targeting.


Assuntos
Antígenos de Superfície/análise , Antígenos de Superfície/imunologia , Carcinoma Neuroendócrino/terapia , Neoplasias da Próstata/terapia , Proteoma/análise , Linfócitos T/transplante , Transcriptoma , Antígeno Carcinoembrionário/genética , Antígeno Carcinoembrionário/imunologia , Antígeno Carcinoembrionário/metabolismo , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/imunologia , Carcinoma Neuroendócrino/metabolismo , Diferenciação Celular , Células Cultivadas , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/imunologia , Proteínas Ligadas por GPI/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Imunoterapia , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , Proteínas de Membrana/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/imunologia , Proteínas de Neoplasias/metabolismo , Próstata/imunologia , Próstata/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/metabolismo , Proteoma/imunologia , Linfócitos T/citologia , Linfócitos T/imunologia
9.
Anticancer Res ; 38(3): 1255-1262, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29491048

RESUMO

BACKGROUND/AIM: Detecting free tumor cells in the peritoneal lavage fluid of gastric cancer patients permits to assess a more accurate prognosis, predict peritoneal recurrence and select cases for a more aggressive treatment. Currently, cytology and molecular biology comprise the two most popular methods of detection that are under constant study by researchers. MATERIALS AND METHODS: We burrowed into the available literature comparing cytological with molecular detection of free intraperitoneal gastric cancer cells. PubMed, Science Direct, Scopus and Google Scholar were the search engines investigated. RESULTS: As of 2017, 51 dedicated studies have been published. Messenger RNA of carcinoembryonic antigen was the genetic target most frequently described. The genetic technique is usually superior to cytology in sensitivity (38-100% vs. 12.3-67% respectively), whereas cytological examination tends to show a slight pre-eminence in specificity (approximately 100%). CONCLUSION: So far, given the imperfection of each method, employment of both cytology and molecular examination seem to be mandatory.


Assuntos
Líquido Ascítico/patologia , Lavagem Peritoneal , Neoplasias Peritoneais/diagnóstico , Neoplasias Gástricas/patologia , Líquido Ascítico/metabolismo , Antígeno Carcinoembrionário/genética , Citodiagnóstico/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Recidiva Local de Neoplasia , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/genética
10.
J Cell Biochem ; 119(4): 3464-3473, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29144000

RESUMO

There were 134,000 new diagnosis and 49,000 deaths in 2016 due to colorectal cancer. Similar to most cancers, early diagnosis increases the chance of successful treatment. Detection of tumor-associated antigens or the immune response against such markers is one of the most common methods of diagnosis. In that regard, we aimed to design and express a chimeric protein from the most common tumor-associated antigens in colorectal cancer and assess its ability to detect the immune response in comparison with the parental tumor-associated antigens in patient's sera. Through bioinformatics approaches a chimeric protein from carcinoembryonic antigen (CEA) and carbohydrate antigen 19.9 (CA19-9) was designed and expressed in E. coli (BL21DE3). Proper folding, expression levels and immune reactivity were assessed by western blot, ELISA and immunohistochemistry. Recombinant proteins functionality and immune reactivity were confirmed by ELISA and Western blot. Results showed that recombinant CEA, recombinant CA19.9 and chimeric protein of CEA- CA19.9 have strong reactivity with antibodies in the sera of colorectal cancer patients, whereas no reactivity was seen with the sera of healthy volunteers. Significantly stronger immune reactivity was seen with the chimeric protein than each of the CEA or CA19.9 alone. Overall, it was concluded that the designed recombinant proteins in this study could be used to detect autoantibodies produced against the colorectal tumor-associated antigens. The chimeric CEA-CA19.9 protein shows a stronger reactivity with the sera antibodies of colorectal cancer patients that CEA or CA19.9 alone.


Assuntos
Antígenos de Neoplasias/metabolismo , Antígeno CA-19-9/metabolismo , Antígeno Carcinoembrionário/metabolismo , Neoplasias Colorretais/metabolismo , Antígenos de Neoplasias/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Western Blotting , Antígeno CA-19-9/genética , Antígeno Carcinoembrionário/genética , Neoplasias do Colo/metabolismo , Neoplasias Colorretais/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino
11.
World J Surg ; 42(3): 749-757, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28875338

RESUMO

BACKGROUND: This report focuses on the surgical manipulation and spread of cancer cells. Our previous study suggested an association between a poor prognosis and positive pleural lavage cytology after resection of esophageal cancer without preoperative treatment. However, little is known regarding the clinical significance of the lavage procedure in esophageal cancer patients who undergo preoperative treatment. METHODS: A cohort of 94 patients with squamous cell carcinoma of the esophagus who underwent esophagectomy with radical lymph node dissection was prospectively analyzed for free cancer cells in the pleural cavity after mediastinal lymphadenectomy. Reverse transcription-polymerase chain reaction was performed to detect free cancer cells in the pleural lavage fluid by measuring squamous cell carcinoma-related antigen (SCC) and carcinoembryonic antigen (CEA). RESULTS: Forty-two patients (44.7%) were positive for SCC after thoracic lymphadenectomy, and 15 patients (15.9%) were positive for CEA. SCC positivity was significantly associated with venous invasion (p = 0.037) and with the clinical response to preoperative treatment (p = 0.001). Furthermore, SCC positivity was associated with poor prognosis compared with negative SCC (p = 0.026). Multivariate analysis revealed that SCC positivity was an independent prognostic factor. Regarding recurrence patterns, SCC positivity tended to be associated with hematogenous recurrence (p = 0.063). Conversely, positive CEA was not associated with any clinicopathological finding, treatment response, prognosis, or recurrence pattern. CONCLUSIONS: Tumor spillage during the evaluated surgical manipulation was assessed in esophageal cancer patients who underwent preoperative treatment. Tumor spillage as evaluated by SCC mRNA was associated with a poor prognosis.


Assuntos
Antígenos de Neoplasias/análise , Antígeno Carcinoembrionário/análise , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Inoculação de Neoplasia , Cavidade Pleural/química , Serpinas/análise , Idoso , Antígenos de Neoplasias/genética , Líquido da Lavagem Broncoalveolar , Antígeno Carcinoembrionário/genética , Esofagectomia , Feminino , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Prognóstico , RNA Mensageiro/análise , Serpinas/genética , Análise de Sobrevida
12.
Biosens Bioelectron ; 99: 193-200, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-28759869

RESUMO

The exploration of electroactive labelling with tailorable and strong differential pulse voltammetry (DPV) responses is of great importance in accurate and sensitive screening of a panel of biomarkers related to cancer. Herein, shell-encoded gold nanoparticles (Au NPs) are fabricated and give rise to shell species-dominated DPV peak potentials. Two independent DPV peaks appear at -0.08V for Au@Cu2O core-shell NPs and 0.26V for Au@Ag core-shell NPs. Shell-encoded Au NPs drastically exhibit shell thickness-tunable amplified peak currents. The non-interfering and amplified DPV responses enable shell-encoded Au NPs to be an alternative electrochemical signal amplifier for dual screening of carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP). The limits of detection (LODs) are calculated to be 1.8pg/mL for CEA and 0.3pg/mL for AFP. In comparison to the parallel single-analyte assays, shell-encoded Au NPs engineered electrochemical aptasensors offer multiplexing capability and show significant prospects in biomedical research and early diagnosis of diseases.


Assuntos
Técnicas Biossensoriais , Antígeno Carcinoembrionário/isolamento & purificação , Diagnóstico Precoce , alfa-Fetoproteínas/isolamento & purificação , Antígeno Carcinoembrionário/genética , Ouro/química , Humanos , Limite de Detecção , Nanopartículas Metálicas/química , alfa-Fetoproteínas/genética
13.
Asian J Surg ; 41(4): 321-327, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28291565

RESUMO

BACKGROUND/OBJECTIVE: Positive carcinoembryonic antigen (CEA) messenger RNA (mRNA) in peritoneal lavage is associated with poor prognosis in patients with colon cancer. However, there are no reports about rectal cancer. Therefore we aimed to evaluate the frequency of positive CEA mRNA in peritoneal lavage and the significance of CEA mRNA in patients with low rectal cancer. METHODS: A total of 55 patients with low rectal cancer who received curative surgical resection were enrolled. CEA mRNA in peritoneal lavage was measured using the transcription-reverse transcription concerted method, a quantitative RNA amplification method. The correlation between CEA mRNA and overall and peritoneal recurrence-free survival was evaluated. RESULTS: Among 55 patients, 6 (10.9%) had positive CEA mRNA in peritoneal lavage. Patients with positive CEA mRNA resulted in significantly higher recurrence rate than those with negative CEA mRNA (p=0.007). Similarly, the local recurrence rate was significantly higher in the positive CEA mRNA group than in the negative CEA mRNA group (p=0.0009). Lymph node metastasis and positive CEA mRNA were independent risk factors for overall and local recurrence. CONCLUSION: Positive CEA mRNA in low rectal cancer is a factor that predisposes patients to a high risk for overall recurrence, especially for local recurrence.


Assuntos
Adenocarcinoma/diagnóstico , Antígeno Carcinoembrionário/metabolismo , Lavagem Peritoneal , Neoplasias Retais/diagnóstico , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno Carcinoembrionário/genética , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/metabolismo , Prognóstico , RNA Mensageiro/metabolismo , Neoplasias Retais/metabolismo , Neoplasias Retais/mortalidade , Neoplasias Retais/terapia , Transcrição Reversa , Taxa de Sobrevida
14.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 40(6): 769-777, 2018 Dec 20.
Artigo em Chinês | MEDLINE | ID: mdl-30606387

RESUMO

Objective To verify the expressions of genes associated with colorectal cancer with hyperglycemia and evaluate their diagnostic values.Methods Tumor tissues,distal normal intestinal mucosa,and peripheral blood samples were harvested from 109 colorectal cancer patients and peripheral blood samples from 30 diabetes patients and 30 healthy volunteers. The mRNA expressions of glucose regulated protein 78 (GRP78),NADPH oxidase-1 (NOX1),carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5),heat shock protein 60 (HSP60),and histone deacetylase 1(HDAC1) were detected by real-time quantitative polymerase chain reaction. The correlation between the gene expressions and clinicopathological parameters in colorectal cancer patients were analyzed using Pearson's correlation analysis. Diagnostic test accuracy evaluation was used to calculate the sensitivity,specificity,accuracy,predictability,Youden index,and likelihood ratio of serum gene expressions in colorectal cancer patients,and the receiver operating characteristic (ROC) curves were drawn. The area under the ROC curve was calculated to evaluate the diagnostic efficiency of the combined detection of multiple genes.Results The mRNA levels of GRP78 (P=0.001),NOX1 (P=0.022),CEACAM5 (P=0.000),HSP60 (P=0.044),and HDAC1 (P=0.047) were positively correlated with the fasting blood glucose level. The mRNA expressions of NOX1 (P=0.000,P=0.008) and HDAC1 (P=0.000,P=0.037) in tissues and serum were significantly higher in colorectal cancer patients than in patients with normal blood glucose levels. The NOX1 mRNA expression was positively correlated with the diameter of colorectal cancer (P=0.013),and the HDAC1 mRNA expression was significantly correlated with the tumor site (P=0.049),depth of primary tumor invasion (P=0.025),and TNM stage (P=0.042). The areas under the ROC curves of NOX1,CEACAM5,and HDAC1 were 0.931,0.852,and 0.860 respectively (all P=0.000). The specificity,accuracy,and negative predictive value of NOX1,HDAC1 mRNA expression in colorectal cancer patients with hyperglycemia were all above 90%. The diagnostic sensitivity and specificity of the combined detection of NOX1,CEACAM5,and HDAC1 were 98.82% and 99.93%,respectively.Conclusion Combined detection of genes associated with colorectal cancer accompanied by hyperglycemia can improve the diagnostic efficiency of early screening.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Hiperglicemia/diagnóstico , Hiperglicemia/genética , Antígeno Carcinoembrionário/genética , Estudos de Casos e Controles , Neoplasias Colorretais/complicações , Diabetes Mellitus/genética , Proteínas Ligadas por GPI/genética , Proteínas de Choque Térmico/genética , Histona Desacetilase 1/genética , Humanos , Hiperglicemia/complicações , NADPH Oxidase 1/genética , Curva ROC
15.
Mol Biol (Mosk) ; 51(6): 1024-1038, 2017 Nov-Dec.
Artigo em Russo | MEDLINE | ID: mdl-29271965

RESUMO

In view of the explosion of the present clinical use of monoclonal antibodies (mAbs), not only in the treatment of cancer, but also of autoimmune diseases, I was asked to review the development of mAbs in tumor diagnosis and therapy, with some illustrations of our own contribution in the field. The initial use of radiolabeled mAbs for tumor targeting and radioimmunotherapy led to the extensive clinical application of unlabeled, "humanized" mAbs for cancer therapy, which I describe with a critical perspective. The introduction of recombinant bispecific antibodies, capable of bridging T lymphocytes with tumor cells and inducing killing of the cancer cells, was found to be mostly active in the treatment of hematological malignancies. Most interestingly, the use of mAbs not directed to the tumor cells, but to inhibitory receptors expressed by cytotoxic T lymphocytes, which trigger them to kill the cancer cells, represents a new form of active cancer immunotherapy. My motivation in writing this review was related to my long-term interactions with several Russian scientists, mentioned at the end of this article.


Assuntos
Anticorpos Monoclonais/farmacologia , Antígeno Carcinoembrionário/imunologia , Neoplasias do Colo/terapia , Neoplasias Hematológicas/terapia , Imunoterapia/métodos , Linfócitos T Citotóxicos/imunologia , Animais , Anticorpos Biespecíficos/biossíntese , Anticorpos Biespecíficos/farmacologia , Anticorpos Monoclonais/biossíntese , Antígeno Carcinoembrionário/química , Antígeno Carcinoembrionário/genética , Engenharia Celular , Neoplasias do Colo/genética , Neoplasias do Colo/imunologia , Neoplasias do Colo/patologia , Citotoxicidade Imunológica , Expressão Gênica , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/patologia , Humanos , Radioisótopos do Iodo , Camundongos , Receptores de Antígenos de Linfócitos T/química , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Coloração e Rotulagem/métodos , Linfócitos T Citotóxicos/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Cell Rep ; 21(11): 3205-3219, 2017 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-29241547

RESUMO

Adoptive therapy with chimeric antigen receptor (CAR)-redirected T cells has achieved remarkable efficacy in the treatment of hematopoietic malignancies. However, eradicating large solid tumors in advanced stages of the disease remains challenging. We explored augmentation of the anti-tumor immune reaction by establishing an acute inflammatory reaction. Systematic screening indicates that IL-18 polarizes CAR T cells toward T-bethigh FoxO1low effectors with an acute inflammatory response. CAR T cells engineered with inducible IL-18 release exhibited superior activity against large pancreatic and lung tumors that were refractory to CAR T cells without cytokines. IL-18 CAR T cell treatment was accompanied by an overall change in the immune cell landscape associated with the tumor. More specifically, CD206- M1 macrophages and NKG2D+ NK cells increased in number, whereas Tregs, suppressive CD103+ DCs, and M2 macrophages decreased, suggesting that "iIL18 TRUCKs" can be used to sensitize large solid tumor lesions for successful immune destruction.


Assuntos
Proteína Forkhead Box O1/imunologia , Imunoterapia Adotiva/métodos , Interleucina-18/imunologia , Neoplasias Pulmonares/terapia , Neoplasias Pancreáticas/terapia , Proteínas com Domínio T/imunologia , Linfócitos T/imunologia , Animais , Antígeno Carcinoembrionário/genética , Antígeno Carcinoembrionário/imunologia , Engenharia Celular , Células Dendríticas/imunologia , Células Dendríticas/patologia , Modelos Animais de Doenças , Proteína Forkhead Box O1/genética , Expressão Gênica , Humanos , Interleucina-18/genética , Interleucina-18/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Macrófagos/imunologia , Macrófagos/patologia , Camundongos , Proteínas Mutantes Quiméricas/genética , Proteínas Mutantes Quiméricas/imunologia , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Cultura Primária de Células , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Análise de Sobrevida , Proteínas com Domínio T/genética , Linfócitos T/patologia , Linfócitos T/transplante , Transgenes , Células Tumorais Cultivadas
17.
Biomed Res Int ; 2017: 3634915, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29238715

RESUMO

2,3,5,4'-Tetrahydroxystilbene-2-O-ß-D-glucoside (THSG) has been shown to have antioxidative and anti-inflammatory effects. Oxidative and inflammatory reactions are related to the development of colorectal carcinoma (CRC). In the present study, we characterized the preventive activities of THSG on colon carcinogenesis using the azoxymethane- (AOM-) mediated rat colon carcinogenesis model. F344 male rats were randomly divided into 5 groups (untreated and AOM model rats treated with or without THSG at 30, 150, or 250 mg/kg) after which the numbers of aberrant crypt foci (ACF) were assessed in the colon tissues of all rats. The expressions of nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), matrix metalloproteinase proteins (MMPs), and carcinoembryonic antigen (CEA) were measured as effective early predictors of CRC using western blot analysis. Treatment with THSG (150 or 250 mg/kg) induced a 50% reduction in total colonic ACF formation (P < 0.05). Furthermore, our results revealed a downregulation of CEA and NF-κB protein levels in the reduced number of ACF elicited by treatment with THSG, whereas levels of COX-2 and MMPs proteins were not changed. Collectively, THSG may be a promising natural lead compound or drug candidate for treating early phases of CRC.


Assuntos
Focos de Criptas Aberrantes/tratamento farmacológico , Anticarcinógenos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Glucosídeos/administração & dosagem , Estilbenos/administração & dosagem , Focos de Criptas Aberrantes/induzido quimicamente , Focos de Criptas Aberrantes/genética , Focos de Criptas Aberrantes/patologia , Animais , Azoximetano/toxicidade , Antígeno Carcinoembrionário/genética , Carcinógenos/toxicidade , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Ciclo-Oxigenase 2/genética , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , NF-kappa B/genética , Ratos
18.
Surg Oncol ; 26(4): 352-358, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29113652

RESUMO

BACKGROUND: We sought to clarify the clinical value of the examination of cancer cells exposed to gastric serosa by our novel method of serosal stamp cytology and a real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. METHOD: A total of 70 patients who underwent gastrectomy were enrolled. Stamp cytology specimens were obtained by stamping the gastric serosa at the primary gastric tumor lesion, followed by Papanicolaou's staining. Samples obtained by brushing the serosa at the primary gastric tumor were analyzed by our RT-PCR of carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20). RESULTS: Among the 70 patients, 11 patients were diagnosed as stamp cytology-positive. Eight and five patients were found to be CEA-positive and CK20-positive, respectively. Since 21 of the 70 patients were either stamp cytology-positive or RT-PCR analysis-positive, these 21 patients were considered to be positive for cancer cells exposed to serosa of primary gastric tumor. The 3-year recurrence-free survival rate of the patients with a single positive result by our method (41.7%) was significantly (log rank p = 0.0002) worse than that of the patients with both negative results (81.0%). Our method showed 58.8% sensitivity and 79.2% specificity. A multivariate analysis revealed that a stamp cytology and/or RT-PCR result was an independent prognostic factor for recurrence. CONCLUSION: The examination of cancer cells exposed to gastric serosa by our serosal stamp cytology and RT-PCR system will be useful for the identification of patients at high risk for peritoneal recurrence after curative surgery for gastric cancer.


Assuntos
Biomarcadores Tumorais/genética , Citodiagnóstico , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Peritoneais/secundário , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Membrana Serosa/patologia , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno Carcinoembrionário/genética , Antígeno Carcinoembrionário/metabolismo , Feminino , Seguimentos , Gastrectomia , Humanos , Queratina-20/genética , Queratina-20/metabolismo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/cirurgia , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/cirurgia , Prognóstico , RNA Mensageiro , Fatores de Risco , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida
19.
IUBMB Life ; 69(12): 956-961, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29131521

RESUMO

Heat shock factor 4 (HSF4) is a member of the HSF family. In this study, by using data from the Cancer Genome Atlas-Colorectal Cancer (TCGA-CRC), we investigated the expression profile and the prognostic value of the HSF4 in terms of overall survival (OS) and recurrence free survival (RFS) in CRC patients. RNA-Seq data showed that HSF4 RNA expression was significantly higher in CRC tissues (N = 380) than in the corresponding normal tissues (N = 51) (mean ± SD: 3.56 ± 1.28 vs. 1.85 ± 0.87, P < 0.0001). High HSF4 expression group had significantly higher ratio of stages III/IV patients (52/86, 60.5%) than low HSF4 expression group (110/264, 41.7%; P = 0.0024). Besides, the high HSF4 expression group also had significantly increased expression of CEA (CEA ≥ 5, 26/51, 51.0% vs. 64/186, 34.4%), higher proportion of recurrence (32/86, 37.2% vs. 48/254, 18.9%, P = 0.0005) and death (36/90, 40.0% vs. 49/277, 17.7%, P < 0.0001) compared with the low HSF4 expression group. Multivariate analysis confirmed that high HSF4 expression was an independent prognostic factor of poor OS (HR = 2.111, 95%CI: 1.350-3.302, P = 0.001) and RFS (HR = 1.958, 95%CI: 1.224-3.131, P = 0.005). Bioinformatic analysis showed that HSF4 can directly interact with DUSP26, ZBED8, and MAPK14. It is also coexpressed with PTGER1, COL11A2, CLPS, and ARSA and colocalized with PTGER1, ADRB1, PEX12, CLPS, PSEN2, KCNJ5, CPA1, ARSA, PNLIP, IRX4, CPA2, IDUA, BCKDHA, and CTRL. We hypothesized that HSF4 might exert its oncogenic effects in CRC via some of these genes. © 2017 IUBMB Life, 69(12):956-961, 2017.


Assuntos
Biomarcadores Tumorais/genética , Antígeno Carcinoembrionário/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Fatores de Transcrição de Choque Térmico/genética , Idoso , Biomarcadores Tumorais/sangue , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Biologia Computacional , Intervalo Livre de Doença , Feminino , Expressão Gênica , Redes Reguladoras de Genes , Fatores de Transcrição de Choque Térmico/sangue , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico
20.
Clin Chim Acta ; 475: 157-163, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29074220

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies worldwide, and early diagnosis is vital to improving prognoses. We explored the diagnostic potential of a multiplex autoantibody panel as a biomarker for the detection of CRC by ELISA. METHODS: In total, 192 serum samples (92 CRC and 100 matched controls) were tested against a panel of 12 tumor-associated antigens (TAAs): RPH3AL, RPL36, SLP2, p53, survivin, ANAXA4, SEC61B, CCCAP, NYCO16, NMDAR, PLSCR1, and HDAC5. Individual and combined autoantibody signatures were examined. RESULTS: Compared to individual autoantibody markers, the combinations of TAAs provided better discrimination between tumorous and normal sera. The overall sensitivity of a selected panel of four antibodies (anti-SLP2, -p53, -SEC61B, and -PLSCR1) was 64.1%, with a specificity of 80% that increased to 83.7% when carcinoembryonic antigen (CEA) measurement was added. Furthermore, the sensitivity of the panel of four antibodies for early and advanced stages of CRC was 66.7% and 62%, increasing to 88.3% and 84%, respectively, when CEA was added. CONCLUSIONS: We identified a panel of four antibodies as a promising diagnostic biomarker for the detection of CRC.


Assuntos
Antígenos de Neoplasias/genética , Autoanticorpos/sangue , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/diagnóstico , Imunoensaio , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/imunologia , Proteínas Sanguíneas/genética , Proteínas Sanguíneas/imunologia , Antígeno Carcinoembrionário/genética , Antígeno Carcinoembrionário/imunologia , Estudos de Casos e Controles , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteínas de Transferência de Fosfolipídeos/genética , Proteínas de Transferência de Fosfolipídeos/imunologia , Prognóstico , Canais de Translocação SEC/genética , Canais de Translocação SEC/imunologia , Sensibilidade e Especificidade , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/imunologia
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