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1.
Cureus ; 16(4): e58549, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38867924

RESUMO

Background Knowledge of the mental foramen (MF) characteristics is crucial for avoiding iatrogenic injuries during dental implant placement, root canal treatment, orthognathic surgery, and other dental and surgical interventions. Cone beam computed tomography (CBCT) offers a valuable tool for evaluating the MF characteristics with its precise anatomical details. The current study investigates the horizontal and vertical position variations in addition to the exit angle of MF within the Syrian adult population. Materials and methods The sample included CBCT scans of 42 subjects with an equal number of males and females (21 males, 21 females), with no underlying pathology in the investigated region, mean age was 24.7 years (SD: 7.2 years). CBCT scans were retrospectively analyzed in terms of the vertical, horizontal, and exit angle direction of MF. The chi-square test was conducted to investigate statistical differences in terms of MF horizontal and vertical positions. A T-test was conducted to investigate statistical differences in terms of exit angle direction. Comparisons were conducted between males and females groups, and between the left and right sides in the total sample group. Results The most frequent horizontal position was position 3 (MF between the first and second premolars) on the right side (n=20, 47.61%), and on the left side (n=21, 50%). The most frequent vertical position was position 3 (MF below the apices of the premolars) on the right side (n=29, 69.04%), and on the left side (n=27, 64.28%). The exit angle of the MF was in a backward direction, with a mean value of 118.42° (SD: 6.45 degrees), and 115.97° (SD: 7.29 degrees) on the right and left side, respectively. Statistically significant differences were found in terms of the right vertical position between males and females (P value < 0.05). Conclusion Variations in MF characteristics exist in the Syrian population. Statistically significant differences were found in the right vertical position of MF. The current study findings necessitate precise preoperative three-dimensional imaging for dental interventions among this population. By establishing normative values for the Syrian population, the results can contribute to improved surgical planning and patient care, and can be used for comparative studies for more understanding of the human anatomical variations.

2.
J Hematol ; 12(3): 128-132, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37435418

RESUMO

Hyperammonemia is a rare cause of encephalopathy in multiple myeloma in the absence of hepatic involvement. This is the only reported case of a 74-year-old man who presented with multiple myeloma and achieved complete remission but developed hyperammonemia afterward. He was aggressively treated with a combination of chemotherapy and immunotherapy, with a resolution of his encephalopathy; however, within one month, he relapsed with encephalopathy. He ultimately decided to pursue comfort-care measures. The authors conclude that hyperammonemia in multiple myeloma is a rare but important differential in patients with encephalopathy of unknown causes. Aggressive treatment is of the utmost importance due to the high mortality associated with the condition.

3.
Cureus ; 13(11): e19552, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34917434

RESUMO

Purpose To report the response of keratoconus (KC) and post-LASIK ectasia (referred to as "ectasia") to the corneal crosslinking (CXL) and to compare the rate of progression between KC and ectasia at three years. Methods A retrospective cohort study of patients undergoing CXL for either KC or ectasia. Fifty-four eyes (31 patients) with ectasia and 111 eyes (67 patients) with KC were included in the study. Corrected distance visual acuities (CDVA), refraction, keratometry (K), and pachymetry were followed up for three years. Simultaneous photorefractive keratectomy (PRK) and CXL were performed on 20 KC and 20 ectasia eyes. Intrastromal Corneal Ring Segments (ICRS) were performed on 51 KC and six ectasia eyes. Results In KC, CDVA, spherical equivalence, sphere, cylinder, and mean K improved at three years post-CXL (p-value<0.05), but these values improved without reaching a statistical significance in ectasia(p-values <0.05). 12 of 54 eyes with ectasia (22.2%) and 4 of 111 eyes (3.6%) with KC had progression post CXL(p-value:0.0001). Ectasia patients diagnosed with progression were older at presentation (36.1 years) than non-progressive ectasia patients (31 years) (p-value 0.02) and also older than KC patients. Sub-analysis excluding PRK and ICRS cases showed that there was an improvement in mean sphere (from -5.23±4.2D to-4.46±3.89D) (p-value 0.03) cylinder (from 2.54 ± 1.68D to 1.97 ± 1.51D) (p-value 0.03) mean keratometry (from 46.81 ± 3.78D to 46.01 ± 3.25D) (p-value 0.006) in KC patients 3 years post CXL (40 patients). Compared to baseline, all the mean refractive and topographic variables deteriorated at three years post CXL in ectasia (28 patients) (p-value>0.05). Also, 2 of 40 patients with KC (5%) vs. 7 of 28 patients with ectasia (25%) had progression three years post-CXL, and the difference between both groups remained statistically significant(p-value 0.027). Conclusion Eyes with post-LASIK ectasia seem to be less responsive to CXL than KC.

4.
Cranio ; : 1-10, 2021 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-33843477

RESUMO

OBJECTIVE: Evaluation of head and cervical spine posture and estimation of sample size. METHODS: Thirty eligible participants who required functional therapy were randomly assigned to the Control group (C), Twin Block group (TB), or the Bionator group (B). Randomization was accomplished by means of blocks of fixed size stratified by sex and age, with the allocations concealed in opaque and sealed envelopes. RESULTS: Significant differences were identified between the pre -and post-functional SNB (p = 0.024) and ANB (p = 0.034) angles in the Twin Block group and SNA (p = 0. 019) and ANB (p = 0. 028) angles in the Bionator group. No statistically significant changes were seen in the head or cervical variables in the three groups. CONCLUSION: The functional appliance did not cause any statistical change in head posture or cervical spinal column in comparison with the non-treatment group.

5.
Mediterr J Hematol Infect Dis ; 8(1): e2016015, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26977274

RESUMO

OBJECTIVE: The objective of this study was to assess the prevalence, gender differences, and time trends of Sickle Cell Trait in the Southern Suburb of Beirut, Lebanon, as well as to highlight the importance of screening for Sickle Cell Trait carriers in this population. Another objective was to describe a new screening technique for Sickle Cell Trait carriers. METHODS: This was a retrospective cohort study carried out at a private laboratory in the Southern Suburb of Beirut, Lebanon between 2002 and 2014. The sickling test was carried out for each patient using two methods: the classical "sodium metabisulfite sickling test", and the new "sickling test method" used in the private lab. As a confirmatory test, hemoglobin electrophoresis was run on a random sample of 223 cases which were found to be positive using the two sickling tests. RESULTS: A total of 899 cases were found to be positive for the sickle cell trait out of 184,105 subjects screened during the 12-year period, prevalence = 0.49% (95% CI: 0.46 - 0.52). Among the total sample, females were found to have higher prevalence, where no time trend over the studied period was noted. The haemoglobin electrophoresis method confirmed the results of this new sickling test technique among the random sample of the 223 cases. CONCLUSION: We found that the prevalence of sickle cell trait is lower as compared to other Arab countries, higher in females, with no significant time trend. The sickle cell test was found to be an accurate, simple and cheap test that could be easily added as a requirement for the pre-marital testing to screen for Sickle Cell Trait carriers.

6.
Oncotarget ; 5(18): 8252-69, 2014 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-25249545

RESUMO

Alterations in the signaling pathways of epidermal growth factor receptors (HERs) are associated with tumor aggressiveness. Neurotensin (NTS) and its high affinity receptor (NTSR1) are up regulated in 60% of lung cancers. In a previous clinical study, NTSR1 overexpression was shown to predict a poor prognosis for 5 year overall survival in a selected population of stage I lung adenocarcinomas treated by surgery alone. In a second study, shown here, the frequent and high expression of NTSR1 was correlated with a pejorative prognosis in 389 patients with stage I to III lung adenocarcinoma, and was an independent prognosis marker. Interactions between NTS and NTSR1 induce pro-oncogenic biological effects associated with neoplastic processes and tumor progression. Here we highlight the cellular mechanisms activated by Neurotensin (NTS) and its high affinity receptor (NTSR1) contributing to lung cancer cell aggressiveness. We show that the NTS autocrine and/or paracrine regulation causes EGFR, HER2, and HER3 over-expression and activation in lung tumor cells. The EGFR and HER3 autocrine activation is mediated by MMP1 activation and EGF "like" ligands (HB-EGF, Neuregulin 1) release. By establishing autocrine and/or paracrine NTS regulation, we show that tumor growth is modulated according to NTS expression, with a low growth rate in those tumors that do not express NTS. Accordingly, xenografted tumors expressing NTS and NTSR1 showed a positive response to erlotinib, whereas tumors void of NTSR1 expression had no detectable response. This is consistent with the presence of a NTS autocrine loop, leading to the sustained activation of EGFR and responsible for cancer aggressiveness. We propose the use of NTS/NTSR1 tumor expression, as a biomarker for the use of EGFR tyrosine kinase inhibitors in patients lacking EGFR mutation.


Assuntos
Adenocarcinoma/tratamento farmacológico , Comunicação Autócrina , Receptores ErbB/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neurotensina/metabolismo , Comunicação Parácrina , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Receptor ErbB-2/metabolismo , Receptor ErbB-3/metabolismo , Receptores de Neurotensina/metabolismo , Adenocarcinoma/enzimologia , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Idoso , Animais , Linhagem Celular Tumoral , Proliferação de Células , Quimioterapia Adjuvante , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Cloridrato de Erlotinib , Feminino , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/metabolismo , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Metaloproteinase 1 da Matriz/metabolismo , Camundongos Nus , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neuregulina-1/metabolismo , Neurotensina/genética , Modelos de Riscos Proporcionais , Receptor ErbB-2/genética , Receptor ErbB-3/genética , Receptores de Neurotensina/genética , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Clin Lung Cancer ; 15(2): 124-30, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24169260

RESUMO

BACKGROUND: In lung adenocarcinoma, inactivation of the tumor suppressor p53 may abrogate a safeguard mechanism preventing the development of tumors with activating mutations in EGFR or KRAS. To assess this hypothesis, we analyzed TP53 mutations and downregulation of p14(arf), a negative regulator of p53 activated by oncogenic signals, in a retrospective series of 96 patients with primary adenocarcinoma of the lung. PATIENTS AND METHODS: Mutations in TP53 (exons 4-9), KRAS (exon 1), and EGFR (exons 18-21) were identified by direct sequencing of DNA from formalin-fixed, paraffin-embedded resected tumors. Expression of p14(arf) was semiquantitatively evaluated by immunohistochemical analysis. RESULTS: TP53, KRAS, and EGFR mutations were detected in 42 of 93 (45.2%), 15 of 95 (15.8%), and 31 of 90 (34.4%) cases, respectively. Low p14(arf) expression was observed in 19 of 91 cases (20.9%). Disruption of the p53/p14(arf) pathway (defined as TP53 mutation or decreased p14(arf) expression, or both) was observed in 18 of 31 EGFR-mutated (58.1%) tumors and in 9 of 13 KRAS-mutated (69.2%) tumors. CONCLUSION: Inactivation of the p53/p14(arf) pathway is common but not systematic in EGFR- or KRAS-mutated lung adenocarcinomas. Our work highlights the need to better investigate the association between EGFR and KRAS mutations and alterations in tumor suppressor pathways.


Assuntos
Receptores ErbB/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Mutação/genética , Proteínas Proto-Oncogênicas/genética , Proteína Supressora de Tumor p14ARF/metabolismo , Proteína Supressora de Tumor p53/genética , Proteínas ras/genética , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , Proteínas Proto-Oncogênicas p21(ras) , Estudos Retrospectivos , Transdução de Sinais
8.
Tex Heart Inst J ; 41(6): 601-2, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25593523

RESUMO

We report our identification of a single coronary ostium arising from the right coronary sinus of Valsalva, in a 63-year-old woman who presented with chest pain atypical of angina. Coronary angiograms showed that the left anterior descending coronary artery arose from a right ventricular branch and that the left circumflex coronary artery arose from a right posterolateral branch. Both arteries reconstituted themselves in a backward fashion from the apex to the base of the heart-a configuration that to our knowledge has not been reported. The patient was treated conservatively and reported no chest pain 24 months later.


Assuntos
Seio Coronário/anormalidades , Anomalias dos Vasos Coronários , Angina Pectoris/etiologia , Aortografia/métodos , Angiografia Coronária/métodos , Seio Coronário/diagnóstico por imagem , Anomalias dos Vasos Coronários/complicações , Anomalias dos Vasos Coronários/diagnóstico por imagem , Anomalias dos Vasos Coronários/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
9.
South Med J ; 106(2): 121-5, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23380746

RESUMO

OBJECTIVES: Macrocytosis is a relatively common finding in adult patients undergoing blood cell counting. Approximately 10% of patients will have unexplained macrocytosis after laboratory evaluation. Data on the approach to patients with unexplained macrocytosis are limited. METHODS: To investigate this topic and help delineate an approach to this condition, the records of 9779 patients diagnosed in our institution between 1995 and 2005 as having macrocytosis were reviewed. Patients with evidence of liver disease, alcohol abuse, hypothyroidism, folate or vitamin B12 deficiency, hemolysis, or use of any drugs known to cause macrocytosis were excluded. RESULTS: Forty-three patients were found to have unexplained macrocytosis. The median follow-up was 4 years. A total of 11.6% patients developed a primary bone marrow disorder (two B-cell lymphomas, two with myelodysplastic syndrome, one plasma cell disorder), 16.3% developed worsening cytopenias, 69.7% had stable disease, and 2.3% resolved. The median time to first cytopenia was 18 months, and the mean time to diagnosis of bone marrow disorder was 31.6 months. The outcomes were not significantly different when comparing patients with or without anemia upon diagnosis. The probability of a bone marrow biopsy to establish a diagnosis of a primary disorder was 33.3% in patients with macrocytosis without anemia compared with 75% in patients with macrocytosis with anemia. CONCLUSIONS: Patients with unexplained macrocytosis still require close follow-up. We suggest a strategy of follow-up with blood cell counting every 6 months. Bone marrow biopsy should be performed when cytopenias are present because this approach may provide a higher yield of diagnosis and aid with therapeutic decisions.


Assuntos
Anemia Macrocítica/diagnóstico , Eritrócitos Anormais , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anemia Macrocítica/complicações , Biópsia , Medula Óssea/patologia , Feminino , Seguimentos , Humanos , Leucopenia/complicações , Modelos Logísticos , Linfoma de Células B/complicações , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/complicações , Paraproteinemias/complicações , Estudos Retrospectivos , Trombocitopenia/complicações
10.
Ann Thorac Surg ; 95(4): 1204-10, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23415237

RESUMO

BACKGROUND: The incidence of vascular and lymphatic emboli in a specimen of resected non-small cell lung cancer is variable according to different authors' experience as well as prognostic significance in patients treated by surgery. We aimed at evaluating these factors in an unselected population of patients with primary pulmonary adenocarcinoma treated by major surgical resection. METHODS: Clinical and pathology records of all patients treated by lobectomy or pneumonectomy and nodal dissection for pulmonary adenocarcinoma between June 2001 and June 2006 were retrospectively reviewed. Impact on survival of age, sex, tobacco use, history of chronic obstructive pulmonary disease, extent of resection, pathologic stage, and presence of vascular and lymphatic emboli was studied by univariate analysis and multivariate analysis (for factors significantly associated with survival at univariate analysis). RESULTS: Five hundred three patients underwent lobectomy or pneumonectomy with nodal dissection for pathologically proven lung adenocarcinoma. There were 355 men and 148 women; mean age was 61.1 years, and 181 patients were 65 years old or older; 87% were current or former smokers; 90.3% had pulmonary lobectomy; and 9.7% had pneumonectomy. Pathologic stages were I, II, and III/IV in 45%, 17.9%, and 37.1%, respectively. Vascular emboli and lymphatic emboli were found in 183 of 503 patients (36.4%) and 149 of 503 (29.6%), respectively. Overall 5-year survival for the whole population was 50.7%. At univariate analysis, age more than 65 years (p=0.0019), chronic obstructive pulmonary disease (p=0.042), extent of resection (p=0.047), pathologic stage (p<0.0000001), T size (p=0.0020), T and N variables (p=0.0000016 and p<0.0000001, respectively), presence of vascular emboli (p=0.026), and presence of lymphatic emboli (p=0.000021) were associated with worse prognosis. At multivariate analysis, age more than 65 years (p=0.0047, relative risk 1.5), stage I versus II versus III versus IV (p=0.00000032), and presence of lymphatic emboli (p=0.05, relative risk 1.34) were identified as independent negative prognostic factors. CONCLUSIONS: In an unselected population of patients with pulmonary adenocarcinoma treated by lobectomy or pneumonectomy, the presence of lymphatic emboli is an independent negative prognostic factor.


Assuntos
Adenocarcinoma/cirurgia , Vasos Sanguíneos , Embolia/mortalidade , Neoplasias Pulmonares/cirurgia , Vasos Linfáticos , Células Neoplásicas Circulantes , Pneumonectomia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Idoso , Embolia/etiologia , Feminino , França/epidemiologia , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida/tendências
11.
J Emerg Med ; 44(2): e157-9, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22494605

RESUMO

BACKGROUND: Bell's palsy is the most common acute mononeuropathy, with an incidence of 20 to 30 cases per 100,000 people per year. OBJECTIVES: Blepharospasm associated with Bell's palsy has been rarely reported. We describe an unusual presentation of Bell's palsy associated with blepharospasm. CASE REPORT: A 44-year-old man presented to the Emergency Department with a few hours' history of right eye blepharospasm. His cornea and conjunctiva were normal on slit lamp examination, including fluorescein staining. His cranial nerves were intact except for a complete right facial nerve weakness, with the patient unable to raise his right eyebrow, and his mouth deviated towards the left. The patient was diagnosed with Bell's palsy associated with blepharospasm and discharged home on prednisone and famciclovir. By the eighth week he was back to baseline with no sequelae. CONCLUSION: Although very rare, physicians should be aware of the existence of Bell's palsy associated with blepharospasm, as it may be under-reported.


Assuntos
Paralisia de Bell/complicações , Blefarospasmo/complicações , 2-Aminopurina/análogos & derivados , 2-Aminopurina/uso terapêutico , Adulto , Antivirais/uso terapêutico , Paralisia de Bell/tratamento farmacológico , Blefarospasmo/tratamento farmacológico , Serviço Hospitalar de Emergência , Famciclovir , Glucocorticoides/uso terapêutico , Humanos , Masculino , Prednisona/uso terapêutico
12.
J Thorac Cardiovasc Surg ; 142(5): 1161-7, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21872279

RESUMO

OBJECTIVE: This study aimed to determine whether preresection serum CRP level independently predicts survival among patients with resectable non-small cell lung cancer. METHODS: Clinical, pathologic, and laboratory data from 300 patients operated on for non-small cell lung cancer in a single institution were studied in univariate and multivariate survival analyses. Validation was sought in another cohort of 68 similar patients from another institution. RESULTS: In the main cohort, preoperative CRP value was 3 mg/L or lower in 136 patients (45.3%), between 4 and 20 mg/L in 89 (29.7%), and greater than 20 in 64 (21.3%). CRP level was significantly associated with chronic bronchitis, hypoalbuminemia, pathologic stage, and peritumoral vascular emboli. Overall, 5-year survivals of patients with preoperative CRP 3 mg/L or lower, between 4 and 20 mg/L, and greater than 20 mg/L were 55.6%, 45.6%, and 40.0%, respectively (P = .0571). In multivariate analysis, CRP level greater than 20 was significantly associated with survival, but with significant interaction between CRP level and disease stage (P = .02). Patients in stage I or II disease with CRP levels greater than 20 had worse survival than did patients with undetectable CRP (adjusted hazard ratio, 1.874; 95% confidence interval, 1.039-3.381); the difference was not significant in stages III and IV. In the validation series, CRP level greater than 20 mg/L also predicted worse survival (P = .018). CONCLUSIONS: Preoperative CRP level greater than 20 mg/L is significantly associated with worse survival than undetectable CRP in patients with stage I or II non-small cell lung cancer.


Assuntos
Proteína C-Reativa/análise , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Procedimentos Cirúrgicos Pulmonares , Idoso , Biomarcadores , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Distribuição de Qui-Quadrado , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paris , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Procedimentos Cirúrgicos Pulmonares/efeitos adversos , Procedimentos Cirúrgicos Pulmonares/mortalidade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
13.
Clin Cancer Res ; 16(17): 4401-10, 2010 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-20810387

RESUMO

PURPOSE: This study aimed to investigate the role of the neurotensin/neurotensin receptor I (NTSR1) complex in non-small cell lung cancer (NSCLC) progression. EXPERIMENTAL DESIGN: The expression of neurotensin and NTSR1 was studied by transcriptome analysis and immunohistochemistry in two series of 74 and 139 consecutive patients with pathologic stage I NSCLC adenocarcinoma. The findings were correlated with clinic-pathologic features. Experimental tumors were generated from the malignant human lung carcinoma cell line A459, and a subclone of LNM35, LNM-R. The role of the neurotensin signaling system on tumor growth and metastasis was investigated by small hairpin RNA-mediated silencing of NTSR1 and neurotensin. RESULTS: Transcriptome analysis carried out in a series of 74 patients showed that the positive regulation of NTSR1 put it within the top 50 genes related with relapse-free survival. Immunohistochemistry revealed neurotensin- and NTSR1-positive staining in 60.4% and 59.7% of lung adenocarcinomas, respectively. At univariate analysis, NTSR1 expression was strongly associated with worse 5-year overall survival rate (P = 0.0081) and relapse-free survival (P = 0.0024). Multivariate analysis showed that patients over 65 years of age (P = 0.0018) and NTSR1 expression (P = 0.0034) were independent negative prognostic factors. Experimental tumor xenografts generated by neurotensin- and NTSR1-silenced human lung cancer cells revealed that neurotensin enhanced primary tumor growth and production of massive nodal metastasis via autocrine and paracrine regulation loops. CONCLUSION: NTSR1 expression was identified as a potential new prognostic biomarker for surgically resected stage I lung adenocarcinomas, as NTSR1 activation was shown to participate in lung cancer progression.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Neurotensina/genética , Receptores de Neurotensina/genética , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Idoso , Animais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Feminino , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Experimentais/genética , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Neurotensina/metabolismo , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Interferência de RNA , Receptores de Neurotensina/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transplante Heterólogo
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