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1.
Int J Clin Oncol ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31832883

RESUMO

BACKGROUND: Head and neck squamous cell carcinomas (HNSCCs) are one of the most common cancers in the world, and nucleotide excision repair (NER) is involved in HNSCCs susceptibility. We investigated whether mRNA expression levels of nine core NER genes were associated with risk of HNSCCs in a Chinese population. METHODS: In this study of 251 HNSCC patients and 232 healthy controls, we quantified NER gene mRNA expression levels in cultured peripheral lymphocytes using a quantitative real-time PCR. RESULTS: Compared with the controls, HNSCC patients had statistically significantly lower expression levels of XPA and XPB (P = 0.029 and 0.001, respectively). After dividing the subjects by the controls' median values of expression levels, we found a dose-dependent association between an increased risk of HNSCCs and low expression levels of XPB (adjusted OR 1.56 and 95% CI 1.07-2.28; Ptrend = 0.001). We also identified a significant multiplicative interaction between smoking status as well as alcohol status and mRNA expression levels of XPB (P = 0.014 and 0.042, respectively). Finally, after integrating demographic variables, we found the addition of smoking status and XPB expression levels to the model significantly improved the sensitivity of the expanded model on HNSCC risk. CONCLUSION: Reduced mRNA expression levels of XPB were associated with an increased risk of HNSCCs in a Chinese population.

2.
ACS Appl Mater Interfaces ; 11(34): 31139-31146, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31368304

RESUMO

A novel, efficient, deep-blue fluorescent emitter mPAC, with a meta-connected donor-acceptor structure containing phenanthroimidazole (PPI) as the donor and phenylcarbazole-substituted anthracene (An-CzP) as the acceptor, was designed and synthesized. The meta-linkage provided a highly twisted molecular conformation, which efficiently interrupts the intramolecular π-conjugation, resulting in a deep-blue emission. The optimized nondoped device based on mPAC displayed a deep-blue emission with a narrow full width at half-maximum of 56 nm and Commission Internationale de L'Eclairage coordinates of (0.16, 0.09). The maximum external quantum efficiency (EQEmax) is 6.76%, corresponding to a high exciton utilization efficiency (EUE) of 59.3-88.9%. Experimental results and theoretical analysis indicated that the high EUE is mainly ascribed to the reverse intersystem crossing (RISC) from T2 to S1, a "hot exciton" path in which the large T2-T1 energy gap (1.45 eV) and small T2-S1 energy difference (0.18 eV, T2 > S1) hamper the internal crossing from T2 to T1 and facilitate the RISC process. For the hot exciton path, the T2 state can be feasibly arranged to a high energy level, forming a thermal equilibrium with S1, even slightly higher than the deep-blue S1 to realize an exergonic RISC process, which is usually difficult for the thermally activated delayed fluorescence emitters.

3.
Clin Nucl Med ; 44(8): 648-649, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31274612

RESUMO

Findings of Tc-DTPA renal scintigraphy of a retroperitoneal malignant peripheral nerve sheath tumor are reported here. The patient was a 48-year-old woman who presented discomfort and intermittent dull pain in the left upper quadrant of the abdomen for approximately 3 weeks.


Assuntos
Rim/diagnóstico por imagem , Neurofibrossarcoma/diagnóstico por imagem , Neurofibrossarcoma/patologia , Neoplasias Retroperitoneais/diagnóstico por imagem , Neoplasias Retroperitoneais/patologia , Pentetato de Tecnécio Tc 99m , Feminino , Humanos , Pessoa de Meia-Idade , Cintilografia
4.
Clin Proteomics ; 16: 20, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31168300

RESUMO

Background: Lung cancer is the leading cause of cancer death in China and around the world. Early detection is key to improving the survival rate of non-small cell lung cancer (NSCLC). Alteration in glycosylation has been observed in cancers, and glycans can be a source for the development of new biomarkers for NSCLC. Methods: In this glycan biomarker discovery study, we measured serum N- and O-glycan profiles in NSCLC patients with different stages and healthy controls by performing lectin microarray analysis. The alterations of serum glycopatterns were compared between NSCLC patients and controls, and the stage-related changes in serum glycosylation were evaluated. Results: There were 18 lectins (e.g., AAL, Jacalin, GSL-I and DBA) to give significantly alterations of serum glycopatterns in lung adenocarcinoma compared with control group. Meanwhile, 16 lectins (e.g., Jacalin, HHL, and PHA-E+L) exhibited significantly alterations of serum glycopatterns in squamous cell carcinoma (SCC) compared with control group. Importantly, most of the lectins showing altered signals exhibited significantly increased or decreased NFIs in patients with early stage adenocarcinoma and SCC. Conclusions: The serum glycan profiles were significantly different between NSCLC and healthy control, and most of the glycosylation changes had occurred at early stage. Further evaluation is needed to examine the diagnostic value of the glycan markers identified in this study.

5.
Clin Nucl Med ; 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31162263

RESUMO

Findings of Tc-DTPA renal scintigraphy of a retroperitoneal malignant peripheral nerve sheath tumor are reported here. The patient was a 48-year-old woman who presented discomfort and intermittent dull pain in the left upper quadrant of the abdomen for approximately 3 weeks.

6.
Artigo em Inglês | MEDLINE | ID: mdl-30828316

RESUMO

Background: The current management of papillary thyroid micro carcinoma (PTMC) has become more conservative. However, high-risk characteristics that can only be revealed post-surgically exist. Patients and clinicians need to estimate the risks and understand the prognostic meaning of these factors. Methods: We retrospectively analyzed 246 consecutive patients with PTMC who underwent surgery at our institution between 2015 and 2017. Clinical and histopathological parameters that may indicate recurrent disease were investigated. The responses to therapy in cases with different risks of recurrence were analyzed. Results: A total of 79.26% (195/246) of patients received total thyroidectomy (TT), of whom 177 (90.77%) also received central lymph node dissection. Radioiodine ablation (RAI) was applied in 64.23% (158/246) of patients. Intermediate-high risk features were identified in 27.64% (68/246) after primary treatment. After a median follow-up of 18 months (range, 6-39 months), 121 of 158 (76.58%) patients who received TT+RAI were evaluated as an excellent response. An incomplete response (IR) was observed in 14.56% (23/158) of this group of PTMC. Multivariate analysis identified extra thyroid extension (P = 0.001) and intermediate-high risk stratification (P = 0.014) as significant and independent risk factors for an IR. Conclusions: A total of 27.64% of PTMC cases evaluated as a low risk of recurrence pre-surgery showed intermediate to high risk disease post-surgery, and this leads to a higher rate of IR.

7.
Nucl Med Commun ; 39(12): 1129-1137, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30239472

RESUMO

OBJECTIVE: The aim of this study was to evaluate the value of technetium-99m methoxyisobutylisonitrile (Tc-MIBI) imaging and ultrasound in preoperative localization of parathyroid adenoma (PA) and parathyroid hyperplasia (PH). PARTICIPANTS AND METHODS: A retrospective study of Tc-MIBI double-phase scintigraphy (DPS) was performed in 187 hyperparathyroidism cases with pathologically diagnosed PA or PH. Of these patients, 167 cases underwent ultrasound, and 146 cases underwent Tc-MIBI single-photon emission computed tomography/computed tomography (SPECT/CT). The sensitivity and diagnostic accuracy of ultrasound, Tc-MIBI DPS, and SPECT/CT were compared between PA and PH. Differences in Tc-MIBI DPS, serum parathyroid hormone (PTH), serum calcium and phosphorus, as well as the weight and longest diameter of lesion between PA and PH were also compared. RESULTS: As per patient-based analysis, the sensitivity of ultrasound, Tc-MIBI DPS, and SPECT/CT was 90.70% (39/43), 95.56% (43/45), and 100.00% (30/30), respectively, for PA, and 93.55% (116/124), 90.85% (129/142), and 93.10% (108/116), respectively, for PH. There were no significant differences in sensitivity of these three imaging methods between PA and PH. However, per lesion-based analysis, the accuracy of ultrasound, Tc-MIBI DPS, and SPECT/CT in detecting PA was 78.43% (40/51), 86.79% (46/53) and 96.88% (31/32), respectively, and the accuracy of Tc-MIBI DPS was higher than that of ultrasound (χ=6.507, P=0.011), and for PH, it was 49.69% (160/322), 40.71% (171/420), and 43.80% (152/347), respectively. The accuracy of ultrasound was higher than that of Tc-MIBI DPS (χ=5.940, P=0.015). The accuracy of a combination of all three examinations of ultrasound+Tc-MIBI DPS, ultrasound+Tc-MIBI SPECT/CT, Tc-MIBI DPS+SPECT/CT, and ultrasound+Tc-MIBI DPS+Tc-MIBI SPECT/CT was 51.51% (154/299), 53.85% (161/299), 50.17% (150/299), and 54.18% (162/299), respectively, which was higher than that of ultrasound (χ=5.273, P=0.022; χ=8.226, P=0.004; χ=3.880, P=0.049; χ=8.702, P=0.003, respectively). Serum levels of PTH and phosphorus were lower in patients with PA than in patients with PH (P<0.001), and serum calcium level, the weight, and the longest diameter of lesion and early uptake rate of Tc-MIBI DPS were higher in patients with PA than in patients with PH (P<0.01). Serum PTH level is often less than 1000 pg/ml in PA, but usually more than 1000 pg/ml in PH. CONCLUSION: Ultrasound, Tc-MIBI DPS, and SPECT/CT all have a higher value in the diagnosis of PA than PH. Tc-MIBI SPECT/CT should be optimal for detecting PA, and early SPECT/CT scan might be better than delayed scan. Compared with Tc-MIBI DPS and SPECT/CT, ultrasound has a slight advantage in localization of PH lesions. The combination of ultrasound and Tc-MIBI DPS or SPECT/CT imaging could improve the accuracy in localization of PH lesions and should be considered as the first-line method for detecting PH.


Assuntos
Adenoma/diagnóstico por imagem , Glândulas Paratireoides/diagnóstico por imagem , Glândulas Paratireoides/patologia , Neoplasias das Paratireoides/diagnóstico por imagem , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Tecnécio Tc 99m Sestamibi , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Hiperplasia/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ultrassonografia , Adulto Jovem
8.
Oncotarget ; 9(3): 3406-3416, 2018 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-29423055

RESUMO

Aims: To investigate the association between angiogenetic activity of hyperplastic thymus and serum thyroglobulin (Tg) level in differentiated thyroid carcinoma patients with thyroglobulin (Tg)-elevated Negative Iodine Scintigraphy (TENIS) Syndrome. Methods: A cohort of 30 consecutive patients who underwent total thyroidectomy followed by radioiodine ablation and had TENIS syndrome received integrin αvß3 targeted imaging with 99mTc-HYNIC-PEG4-E[PEG4-c(RGDfk)]2 (99mTc-3PRGD2). The correlation of angiogenetic activity of the thymus and the serum Tg levels was evaluated in patients with enlarged thymus. Results: Enlarged thymus was detected in 9 out of the 30 TENIS patients and all hyperplastic thymus showed an increased accumulation of the tracer (median tumor/background ratio: 2.8). Five of them had only mediastinal uptake and surgical removal of the mediastinal mass in one provided histopathologic evidence of thymic tissue. The other four were not assigned further treatment and were free of disease in the follow-up, though their stimulated Tg levels consistently increased. Four out of the 9 patients showed 99mTc-3PRGD2 uptake outside the mediastinum were assigned surgery followed by radioiodine treatment. Their stimulated Tg levels decreased after iodine ablation, but not drop back to normal. A significant linear correlation was observed between serum Tg levels and the degree of angiogenesis in the hyperplastic thymus. Conclusions: The angiogenetic activity in hyperplastic thymus was related with the consistently elevated serum Tg levels in TENIS syndrome patients. Based on the existing literature and current data, we propose further intervention for patients with RGD uptake outside thymus, while close follow-up for patients with only mediastinal uptake.

9.
Sci Rep ; 8(1): 473, 2018 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-29323252

RESUMO

The aim of this study was to assess the usefulness of integrin imaging with 99mTc-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2) single photon emission computed tomography (SPECT)/computed tomography (CT) in detecting recurrent disease in patients with differentiated thyroid cancer (DTC), negative radioiodine whole-body scan (WBS) and high serum thyroglobulin (Tg). Thirty-seven patients who underwent total thyroidectomy followed by radioactive iodine ablation and had negative radioiodine WBS but elevated Tg levels were included. 99mTc-3PRGD2 SPECT/CT was performed 1 week after the negative diagnostic 131I WBS. Diagnostic performance indicators, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), for 99mTc-3PRGD2 SPECT/CT was calculated. The correlations between SPECT/CT results and clinic-pathological characteristics were examined. In 30 (81.1%) of the 37 patients, 99mTc-3PRGD2 SPECT/CT showed positive uptake. The sensitivity, specificity, PPV, and NPV of SPECT/CT to detect recurrent disease at follow-up were 96.6%, 75%, 93.3% and 85.7%, respectively. The sensitivity and PPV of SPECT/CT increased with increasing serum Tg levels. 99mTc-3PRGD2 SPECT/CT showed high sensitivity and PPV in the detection of recurrence among DTC patients with higher Tg levels and negative WBS, and the probability of obtaining a positive SPECT/CT result was related with the level of Tg.


Assuntos
Compostos Radiofarmacêuticos/química , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Tireoglobulina/sangue , Neoplasias da Glândula Tireoide/diagnóstico , Imagem Corporal Total , Adolescente , Adulto , Idoso , Feminino , Humanos , Radioisótopos do Iodo/química , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Compostos de Organotecnécio/química , Peptídeos Cíclicos/química , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia , Adulto Jovem
10.
Sci Rep ; 7: 40151, 2017 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-28057933

RESUMO

The role of telomere in genomic stability is an established fact. Variation in leukocyte telomere length (LTL) has been considered a crucial factor that associated with age-associated diseases. To elucidate the association between LTL variation and ischemic stroke (IS) risk, we selected ten single nucleotide polymorphisms (SNPs) in three genes (TERC, TERT and RTEL1) that previously reported link to LTL, and genotyped SNPs of these genes in a case-control study. The association between polymorphisms and IS risk were tested by Chi squared test and haplotype analysis. In allele association analysis, allele "C" in rs10936599 of TERC gene and allele "G" in rs2853677 of TERT gene were found to have an increased risk of IS when compared with allele "T" and "A", respectively. Model association analysis showed that genotype "G/A" in the overdominant model and genotypes "G/A" and "A/A" in the dominant model of rs2242652 presented a more likelihood to have IS. Another TERT locus (rs2853677) with genotype "G" was also found IS-related risky in the log-additive model. Taken together, our results suggest a potential association between LTL related TERC, TERT gene variants and ischemic stroke risk.


Assuntos
Isquemia Encefálica/genética , Leucócitos/metabolismo , Polimorfismo de Nucleotídeo Único , RNA/genética , Acidente Vascular Cerebral/genética , Telomerase/genética , Telômero/metabolismo , Grupo com Ancestrais do Continente Asiático/genética , Isquemia Encefálica/complicações , China , DNA Helicases/genética , Humanos , Acidente Vascular Cerebral/complicações , Homeostase do Telômero
11.
Mol Neurobiol ; 54(8): 5988-5995, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27686078

RESUMO

The development of ischemic stroke is associated with advanced age. Telomere length, as a marker of biological aging, has been reported to influence the risk of several age-related diseases, including ischemic stroke. Recent studies have identified the genetic variant within ACYP2 and TSPYL6 associated with shorter telomere length. The objective of this study is to investigate the putative association of ischemic stroke with common polymorphisms in ACYP2 and TSPYL6 genes in a Chinese Han population. We found that the risk alleles of six single nucleotide polymorphisms (SNPs), including rs11125529, rs12615793, rs843711, rs11896604, and rs843706 within both ACYP2 and TSPYL6, and rs17045754 in ACYP2 gene, were related with increased risk of ischemic stroke according to both allelic and genotype association analyses. The significant correlations between ACYP2 and TSPYL6 SNPs and ischemic stroke risk were also observed in dominant, recessive, and additive models, respectively. Two blocks in high linkage disequilibrium were identified in this study, and two haplotypes were associated with higher ischemic stroke susceptibility. In conclusion, the genetic polymorphisms of ACYP2 and TSPYL6 are associated with increased risk of developing ischemic stroke. Further studies with larger sample sizes are required to validate our findings.


Assuntos
Hidrolases Anidrido Ácido/genética , Isquemia Encefálica/genética , Predisposição Genética para Doença , Proteínas Nucleares/genética , Acidente Vascular Cerebral/genética , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Risco
12.
Clin Chim Acta ; 464: 118-122, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27876462

RESUMO

BACKGROUND: S100 family of calcium-binding proteins plays a significant role in the process of many kinds of tumors, including lung cancer. As an important member of this family, S100 calcium binding protein A2 (S100A2) has been confirmed to be associated with many biological processes, and has an abnormal expression in non-small cell lung cancer (NSCLC). However, the S100A2 status in lung cancer is still controversial and undefined. METHODS: We evaluated the pattern and distribution of S100A2 in 109 cases of lung cancer, including five histological types (47 adenocarcinoma, 46 squamous cell carcinoma, 7 small cell carcinoma, 3 large cell carcinoma, and 6 atypical carcinoid), and 30 cases of paired adjacent normal lung tissues by means of immunohistochemistry. RESULTS: Compared with the normal tissues (0/30), S100A2 experienced a dramatically upward trend of positive expression in lung cancer, with a positive rate of 68/109 (P<0.001). Specifically, squamous cell carcinoma, with 34/12, had the highest expression ratio, followed by large cell carcinoma (2/1), adenocarcinoma (31/16), and atypical carcinoid (1/5) respectively, while no S100A2 protein was detected in small cell carcinoma. Meanwhile, we firstly demonstrated that the high expression of S100A2 was significantly associated with the incidence of lymph node metastasis in adenocarcinoma (P=0.013). CONCLUSIONS: The association between high S100A2 expression and NSCLC at the level of tissue, and S100A2 may serve as an effective biomarker for the diagnosis and prognosis of NSCLC in future.


Assuntos
Grupo com Ancestrais do Continente Asiático/etnologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Fatores Quimiotáticos/metabolismo , Grupos Étnicos , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/patologia , Proteínas S100/metabolismo , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade
13.
Oncotarget ; 7(41): 67277-67287, 2016 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-27572309

RESUMO

NVP-BKM120 (BKM120) is a new pan-class I phosphatidylinositol-3 kinase (PI3K) inhibitor and has been tested in clinical trials as an anticancer agent. In this study, we determined whether BKM120 induces autophagy and the impact of autophagy induction on BKM120's growth-inhibitory activity. BKM120 potently induced elevation of autophagosome-bound type II LC3 (LC3-II) protein, predominantly in cell lines insensitive to BKM120, thereby inducing autophagy. The presence of lysosomal protease inhibitor chloroquine further enhanced the levels of LC3-II. BKM120 combined with chloroquine, enhanced growth-inhibitory effects including induction of apoptosis, suggesting that autophagy is a protective mechanism counteracting BKM120's growth-inhibitory activity. Interestingly, BKM120 increased p-ERK1/2 levels. When blocking the activation of this signaling with MEK inhibitors or with knockdown of ERK1/2, the ability of BKM120 to increase LC3-II was attenuated and the growth-inhibitory effects including induction of apoptosis were accordingly enhanced, suggesting that the MEK/ERK activation contributes to BKM120-induced authophagy. In mouse xenograft model, we also found that the combination of BKM120 and PD0325901 synergistically suppressed cell growth in human lung cancer cells. Thus, the current study not only reveals mechanisms accounting for BKM120-induced autophagy, but also suggests an alternative method to enhance BKM120's therapeutic efficacy against non-small cell lung cancer(NSCLC) by blocking autophagy with either a lysosomal protease inhibitor or MEK inhibitor.


Assuntos
Aminopiridinas/farmacologia , Autofagia/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Morfolinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cloroquina/farmacologia , Inibidores Enzimáticos/farmacologia , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Tumour Biol ; 37(8): 11177-86, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26935060

RESUMO

MicroRNAs (miRNAs) play a critical role in cancer development and progression. Deregulated expression of miR-204 has been reported in several cancers, but the mechanism through which miR-204 modulates human non-small cell lung cancer (NSCLC) is largely unknown. In this study, we investigate the expression and functional role of miR-204 in human NSCLC tissues and cell lines. RNA isolation, qRT-PCR, MTT, colony formation assay, cell cycle assay, cell apoptosis assay, cell migration assay, and Western blot were performed. Statistical analysis was performed using SPSS 18.0 software and statistical significance was accepted at p value <0.05. miR-204 level was significantly reduced in NSCLC tissues as compared to that of non-neoplastic tissues. Transient over-expression of miR-204 by transfecting with miR-204 mimics suppressed NSCLC cell proliferation, migration, and induced apoptosis and G1 arrest, whereas inhibition of miR-204 showed the converse effects. Additionally, activating transcription factor 2 (ATF2), an important transcription factor, was demonstrated as a potential target gene of miR-204. Subsequent investigations found a negative correlation between miR-204 level and ATF2 expression in NSCLC tissue samples. Moreover, we observed that miR-204 expression inversely affected endogenous ATF2 expression at both mRNA and protein levels in vitro. Taken together, miR-204 may act as a tumor suppressor by directly targeting ATF2 in NSCLC.


Assuntos
Fator 2 Ativador da Transcrição/biossíntese , Carcinoma Pulmonar de Células não Pequenas/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Fator 2 Ativador da Transcrição/genética , Adulto , Idoso , Apoptose/genética , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Transfecção
15.
Tumour Biol ; 37(2): 2299-304, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26361956

RESUMO

Biochemical markers play a significant role in the diagnosis of lung cancer. Recent studies have demonstrated a link involving S100 Calcium Binding Proteins (S100A2, S100A6) and non-small cell lung cancer (NSCLC), but the expediency of their serum levels in NSCLC has not been established. In this study, we evaluate the potential of serum S100A2 and S100A6 levels as diagnostic markers for NSCLC. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of S100A2 and S100A6 in 141 NSCLC patients and 150 healthy subjects. Serum levels of the two proteins in patients with NSCLC were higher compared to healthy controls (P = 0.0002 for S100A2 and P < 0.0001 for S100A6). Moreover, the levels of S100A2 and S100A6 were higher in the sera of stage I/II NSCLC patients compared to healthy controls with P = 0.01 and <0.0001, respectively. Receiver operating characteristic (ROC) analysis showed that S100A2 could distinguish NSCLC patients from healthy controls (AUC = 0.646), and S100A6 could also identify NSCLC (AUC = 0.668). Meanwhile, these two proteins showed notable capabilities for distinguishing stage I/II NSCLC from healthy controls (AUC = 0.708 for S100A2 and AUC = 0.702 for S100A6). Our results indicate that serum levels of S100A2 and S100A6 are significantly elevated in early stage NSCLC and may have the potential for NSCLC biomarker. Further studies with large sample population would help validate our findings.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Proteínas de Ciclo Celular/sangue , Fatores Quimiotáticos/sangue , Neoplasias Pulmonares/diagnóstico , Proteínas S100/sangue , Adulto , Idoso , Área Sob a Curva , Carcinoma Pulmonar de Células não Pequenas/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Curva ROC , Proteína A6 Ligante de Cálcio S100 , Sensibilidade e Especificidade
16.
Dis Markers ; 2015: 824304, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25999661

RESUMO

The role of genetics in progression of cancer is an established fact, and susceptibility risk and difference in outcome to chemotherapy may be caused by the variation in low-penetrance alleles of risk genes. We selected seven genes (CRP, GPC5, ACTA2, AGPHD1, SEC14L5, RBMS3, and GKN1) that previously reported link to lung cancer (LC) and genotyped single nucleotide polymorphisms (SNPs) of these genes in a case-control study. A protective allele "C" was found in rs2808630 of the C-reactive protein (CRP). Model association analysis found genotypes "T/C" and "C/C" in the dominant model and genotype "T/C" in the overdominant model of rs2808630 associated with reduced LC risk. Gender-specific analysis in each model showed that genotypes "T/T" and "C/C" in rs2352028 of the Glypican 5 (GPC5) were associated with increased LC risk in males. Logistic regression analysis showed "C/T" genotype carriers of rs4254535 in the Gastrokine 1 (GKN1) had less likelihood to have chemotherapy response. Our results suggest a potential association between CRP and GPC5 variants with LC risk; variation in GKN1 is associated with chemotherapy response in the Chinese Han population.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Glipicanas/genética , Neoplasias Pulmonares/genética , Hormônios Peptídicos/genética , Polimorfismo de Nucleotídeo Único , Proteínas de Transporte Vesicular/genética , Adulto , Grupo com Ancestrais do Continente Asiático/etnologia , Estudos de Casos e Controles , China/etnologia , Cisplatino/uso terapêutico , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/etnologia , Masculino , Pessoa de Meia-Idade
17.
Tumour Biol ; 36(6): 4357-65, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25874488

RESUMO

MicroRNAs (miRNAs) play a critical role in cancer development and progression. Aberrant expression of miR-15a has recently been reported in several cancers, but its role in non-small cell lung cancer (NSCLC) still remains obscure. We investigated the effects of miR-15a on proliferation, apoptosis, and metastasis in A549 cells. Eighteen paired NSCLC and adjacent non-tumor lung tissues were surgically removed and immediately snap frozen until total RNA was extracted and confirmed by two independent pathologists. The targets of miR-15a were predicted by bioinformatics tools. RNA isolation and quantitative real-time PCR (qRT-PCR), Western blot analysis, cell proliferation assay, cell cycle analysis, cell apoptosis assay, and migration and invasion assays were done. The wild type (WT) or mutant type (MT) 3'-untranslated region (UTR) vectors were co-transfected with miR-15a or negative control into A549 cells, and after 24 h of transfection, luciferase activity was measured using the Dual-Glo luciferase assay kit. Statistical analysis was performed using SPSS 13.0 software (SPSS, Chicago, IL, USA). P values of less than 0.05 were considered statistically significant. miR-15a was significantly downregulated in NSCLC than in adjacent non-cancerous tissues. miR-15a overexpression remarkably inhibited cell viability, invasion, and migration and promoted the apoptosis of NSCLC cells. Additionally, inhibition of miR-15a expression had the opposite effects on tumor progression, while cell cycle remained unaltered. Furthermore, we identified that BCL2L2 was a target of miR-15a and negatively regulated by miR-15a at the translational level. miR-15a acts as a tumor suppressor in NSCLC by directly targeting BCL2L2 and may serve as a potential diagnostic biomarker and therapeutic target for NSCLC.


Assuntos
Proteínas Reguladoras de Apoptose/biossíntese , Biomarcadores Tumorais/biossíntese , Carcinoma Pulmonar de Células não Pequenas/genética , MicroRNAs/genética , Apoptose/genética , Proteínas Reguladoras de Apoptose/genética , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Neoplásica
18.
Glycobiology ; 25(3): 331-40, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25347993

RESUMO

Lung cancer is the most common malignancy worldwide. Thus, there is a critical need for diagnostic biomarkers with adequate sensitivity and specificity for lung cancer detection. Glycans in glycoproteins are significantly altered in cancer, and may serve as a tool for identifying potential diagnostic biomarkers. Recent studies have reported changes in α-1-antitrypsin (A1AT) glycosylation in lung cancer serum, tissue and cell lines. In this study, a lectin microarray was used to detect glycosylation changes in serum A1AT from patients with lung adenocarcinoma (ADC), squamous cell lung cancer, small-cell lung cancer (SCLC) and benign pulmonary diseases. Differentially expressed glycosylated patterns of A1AT were identified by lectin arrays and were confirmed by lectin-based enzyme-linked immunosorbent assay (ELISA). We found that galactosylated A1AT could distinguish non-small-cell lung cancer (NSCLC) from benign pulmonary diseases (AUC = 0.834); fucosylated A1AT showed exceptional capability in distinguishing ADC from benign diseases (AUC = 0.919) or other lung cancer subtypes (AUC = 0.844), and A1AT containing poly-LacNAc could detect SCLC from benign diseases (AUC = 0.905) or NSCLC (AUC = 0.707). The present study indicates that glycosylated patterns of A1AT may serve as potential biomarkers for detection of lung cancer. Further studies in larger sample sizes are necessary to validate the clinical utility of these markers.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Neoplasias Pulmonares/sangue , Processamento de Proteína Pós-Traducional , alfa 1-Antitripsina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Casos e Controles , Feminino , Glicosilação , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , alfa 1-Antitripsina/metabolismo
19.
Eur J Cancer Prev ; 23(6): 497-501, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25254308

RESUMO

Lung cancer has the highest mortality rate among cancers; however, its nosogenesis is still unclear. Genome-wide association studies have shown that the telomerase reverse transcriptase (TERT) gene, located in the chromosome 5p15.33 region, is one of the genes associated with the risk of lung cancer. In this case-control study, we genotyped 11 tag single-nucleotide polymorphisms of the TERT gene to evaluate their association with lung cancer risk in the Han Chinese population. Two tag single-nucleotide polymorphisms were found to be associated with lung cancer risk on using the χ2-test: rs4246742 [odds ratio (OR)=0.77, 95% confidence interval (CI) 0.60-0.98; P=0.03] and rs2853672 (OR=1.26, 95% CI 1.01-1.57; P=0.045). By using SNPStats software we also found rs2242652 (OR=1.47, 95% CI 1.02-2.13; P=0.04) in the dominant model and rs2736098 (OR=1.38, 95% CI 1.06-1.80; P=0.017), rs2853672 (OR=1.41, 95% CI 1.11-1.80; P=0.0048), and rs4246742 (OR=0.75, 95% CI 0.58-0.97; P=0.029) in the log-additive model. 'T/C-T/T' of rs10069690 conferred an increased risk for male sex in the dominant model (OR=1.80, 95% CI, 1.05-3.08; P=0.03) and 'TC' increased risk for male sex in the overdominant model (OR=1.85, 95% CI, 1.08-3.17; P=0.031). Our findings, combined with previous studies, suggest that polymorphisms in the TERT gene contribute to the risk for lung cancer in the Chinese Han population.


Assuntos
Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Telomerase/genética , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco
20.
Tumour Biol ; 35(12): 12075-82, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25155038

RESUMO

The implication of genetic factors in predisposition to cancer is a recognized fact. The Cleft lip and palate transmembrane 1-like (CLPTM1L) gene resides in a locus in the chromosome 5p15.33 region that is associated with lung cancer susceptibility and has a role in carcinogenesis. We conducted a case-control study in a Chinese population of 309 pathologically confirmed lung cancer patients and 310 controls to investigate the effect of variant genotypes within the CLPTM1L locus on susceptibility to lung cancer and sensitivity to cisplatin-based chemotherapy. We genotyped nine single nucleotide polymorphisms (SNPs) within the CLPTM1L locus and examined their correlation with lung cancer risk and treatment response using χ (2) and unconditional logistic regression analysis. We identified rs451360 as a novel SNP associated with lung cancer risk in the Chinese Han population. The "T" allele of rs451360 was associated with decreased risk of lung cancer (p = 0.007, odd ratio (OR) = 0.59, 95 % confidence interval (CI): 0.40-0.87). Significant multiplicative interactions were observed between gender and polymorphisms of rs402710, the "T/T" genotype of which was associated with decreased lung cancer risk in male patients (p = 0.016, OR = 0.35, 95 % CI: 0.17-0.73). CLPTM1L polymorphisms did not affect the tumor sensitivity to cisplatin combination chemotherapy in our study patients. The results of the present study suggest a potential association between CLPTM1L variants and lung cancer risk in the Chinese Han populations.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Alelos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Casos e Controles , Cisplatino/administração & dosagem , Frequência do Gene , Genótipo , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Fatores de Risco , Resultado do Tratamento
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