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1.
J Comput Assist Tomogr ; 40(4): 560-3, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27023857

RESUMO

Post-radiation therapy evaluation of distal esophageal cancers with positron emission tomography/computed tomography can be problematic. Differentiation of recurrent neoplasm from postradiation changes is difficult in areas of fluorodeoxyglucose avidity in adjacent, incidentally irradiated organs. Few studies have described the magnetic resonance imaging appearance of radiation-induced hepatic injury. We report a case of focal radiation-induced liver injury with a new focus of fluorodeoxyglucose uptake on posttreatment positron emission tomography as well as masslike enhancement and signal abnormality on magnetic resonance imaging, thus mimicking new liver metastasis. Correlation with radiation planning images suggested the correct diagnosis, which was confirmed on follow-up imaging.


Assuntos
Neoplasias Esofágicas/radioterapia , Hepatopatias/diagnóstico por imagem , Hepatopatias/etiologia , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Lesões por Radiação/diagnóstico por imagem , Diagnóstico Diferencial , Neoplasias Esofágicas/diagnóstico por imagem , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Lesões por Radiação/etiologia , Radioterapia Conformacional/efeitos adversos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
2.
Eur J Cardiothorac Surg ; 65(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38011656

RESUMO

OBJECTIVES: A study of tumour metabolic reprogramming has revealed disease biomarkers and avenues for therapeutic intervention. Metabolic reprogramming in thymoma is currently understudied and largely unknown. This study utilized metabolomics and isotope tracing with 13C-glucose to metabolically investigate thymomas, adjacent thymic tissue and benign thymic lesions. METHODS: From 2017 to 2021, 20 patients with a suspected thymoma were recruited to this prospective Institutional Review Board approved clinical trial. At the time of surgery, 11 patients were infused with 13C-glucose, a stable, non-radioactive tracer which reports the flow of carbon through metabolic pathways. Samples were analysed by mass spectrometry to measure the abundance of >200 metabolites.13C enrichment was measured in patients who received 13C-glucose infusions. RESULTS: Histological analysis showed that 9 patients had thymomas of diverse subtypes and 11 patients had benign cysts. In our metabolomic analysis, thymomas could be distinguished from both adjacent thymus tissue and benign lesions by metabolite abundances. Metabolites in pyrimidine biosynthesis and glycerophospholipid metabolism were differentially expressed across these tissues.13C-glucose infusions revealed differential labelling patterns in thymoma compared to benign cysts and normal thymus tissue. The lactate/3PG labelling ratio, a metabolic marker in aggressive lung tumours correlated with lactate uptake, was increased in thymomas (1.579) compared to normal thymus (0.945) and benign masses (0.807) (thymic tissue versus tumour P = 0.021, tumour versus benign P = 0.013). CONCLUSIONS: We report metabolic biomarkers, including differential 13C labelling of metabolites from central metabolism, that distinguish thymomas from benign tissues. Altered glucose and lactate metabolism warrant further investigation and may provide novel therapeutic targets for thymoma.


Assuntos
Cistos , Timoma , Neoplasias do Timo , Humanos , Timoma/diagnóstico , Timoma/cirurgia , Timoma/patologia , Estudos Prospectivos , Neoplasias do Timo/diagnóstico , Neoplasias do Timo/cirurgia , Neoplasias do Timo/patologia , Biomarcadores , Glucose , Lactatos
3.
Eur J Cardiothorac Surg ; 65(4)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38547389

RESUMO

OBJECTIVES: Spontaneous sternoclavicular joint infection (SSCJI) is a rare and poorly understood disease process. This study aims to identify factors guiding effective management strategies for SSCJI by using data mining. METHODS: An Institutional Review Board-approved retrospective review of patients from 2 large hospitals (2010-2022) was conducted. SSCJI is defined as a joint infection without direct trauma or radiation, direct instrumentation or contiguous spread. An interdisciplinary team consisting of thoracic surgeons, radiologists, infectious disease specialists, orthopaedic surgeons, hospital information experts and systems engineers selected relevant variables. Small set data mining algorithms, utilizing systems engineering, were employed to assess the impact of variables on patient outcomes. RESULTS: A total of 73 variables were chosen and 54 analysed against 11 different outcomes. Forty-seven patients [mean age 51 (22-82); 77% male] met criteria. Among them, 34 underwent early joint surgical resection (<14 days), 5 patients received delayed surgical intervention (>14 days) and 8 had antibiotic-only management. The antibiotic-only group had comparable outcomes. Indicators of poor outcomes were soft tissue fluid >4.5 cm, previous SSCJI, moderate/significant bony fragments, HgbA1c >13.9% and moderate/significant bony sclerosis. CONCLUSIONS: This study suggests that targeted antibiotic-only therapy should be considered initially for SSCJI cases while concurrently managing comorbidities. Patients displaying indicators of poor outcomes or no symptomatic improvement after antibiotic-only therapy should be considered for surgical joint resection.


Assuntos
Artrite Infecciosa , Articulação Esternoclavicular , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Articulação Esternoclavicular/diagnóstico por imagem , Articulação Esternoclavicular/cirurgia , Artrite Infecciosa/tratamento farmacológico , Artrite Infecciosa/cirurgia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Antibacterianos/uso terapêutico
4.
J Thorac Oncol ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38447919

RESUMO

INTRODUCTION: The TNM classification of lung cancer is periodically revised. The International Association for the Study of Lung Cancer collected and analyzed a new database to inform the forthcoming ninth edition of the TNM classification. The results are herewith presented. METHODS: After exclusions, 76,518 patients from a total of 124,581 registered patients were available for analyses: 58,193 with clinical stage, 39,192 with pathologic stage, and 62,611 with best stage NSCLC. The proposed new N2 subcategories (N2a, involvement of single ipsilateral mediastinal or subcarinal nodal station, and N2b, involvement of multiple ipsilateral mediastinal nodal stations with or without involvement of the subcarinal nodal station) and the new M1c subcategories (M1c1, multiple extrathoracic metastases in one organ system, and M1c2, multiple extrathoracic metastases in multiple organ systems) were considered in the survival analyses. Several potential stage groupings were evaluated, using multiple analyses, including recursive partitioning, assessment of homogeneity within and discrimination between potential groups, clinical and statistical significance of survival differences, multivariable regression, and broad assessment of generalizability. RESULTS: T1N1, T1N2a, and T3N2a subgroups are assigned to IIA, IIB, and IIIA stage groups, respectively. T2aN2b and T2bN2b subgroups are assigned to IIIB. M1c1 and M1c2 remain in stage group IVB. Analyses reveal consistent ordering, discrimination of prognosis, and broad generalizability of the proposed ninth edition stage classification of lung cancer. CONCLUSIONS: The proposed stages for the ninth edition TNM improve the granularity of nomenclature about anatomic extent that has benefits as treatment approaches become increasingly differentiated and complex.

5.
Tumour Biol ; 33(2): 287-96, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22143938

RESUMO

Changes in DNA methylation patterns are an important characteristic of human cancer including lung cancer. In particular, hypermethylation of CpG islands is a signature of malignant progression. Methylated CpG islands are promising diagnostic markers for the early detection of cancer. However, the full extent and sequence context of DNA hypermethylation in lung cancer has remained unknown. We have used the methylated CpG island recovery assay and high-resolution microarray analysis to find hypermethylated CpG islands in squamous cell carcinomas (SCC) and adenocarcinomas of the lung. Each tumor contained several hundred hypermethylated CpG islands. In an initial microarray screen, 36 CpG islands were methylated in five of five (=100%) of the SCC tumors tested and 52 CpG islands were methylated in at least 75% of the adenocarcinomas tested (n=8). Using sodium-bisulfite-based approaches, 12 CpG islands (associated with the BARHL2, EVX2, IRX2, MEIS1, MSX1, NR2E1, OC2, OSR1, OTX1, PAX6, TFAP2A, and ZNF577 genes) were confirmed to be methylated in 85% to 100% of the squamous cell carcinomas and 11 CpG islands (associated with the CHAD, DLX4, GRIK2, KCNG3, NR2E1, OSR1, OTX1, OTX2, PROX1, RUNX1, and VAX1 genes) were methylated in >80% of the adenocarcinomas. From the list of genes that were methylated in lung adenocarcinomas, we identified the gene FAT4 and found that this gene was methylated in 39% of the tumors. FAT4 is the closest mammalian homologue of the Drosophila tumor suppressor Fat which is an important component of the Hippo growth control pathway. Many of these newly discovered methylated CpG islands hold promise for becoming biomarkers for the early detection of lung cancer.


Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma de Pulmão , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Ilhas de CpG , Perfilação da Expressão Gênica/métodos , Humanos , Neoplasias Pulmonares/genética , Modelos Biológicos , Análise de Sequência com Séries de Oligonucleotídeos
6.
Biomarkers ; 17(4): 372-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22515502

RESUMO

OBJECTIVES: To evaluate the diagnostic values of autoantibodies against lymphocyte antigen 6 complex locus K (LY6K) in esophageal squamous cell carcinoma (ESCC). METHODS: After cloning, expressing, and purifying LY6K as fusion proteins, LY6K autoantibodies were measured in 62 patient and 58 control serum samples using enzyme-linked immunosorbent assay (ELISA). Reverse transcription polymerase chain reaction (RT-PCR) was used to measure the LY6K mRNA levels in ESCC and adjacent tissues. RESULTS: LY6K autoantibodies were found significantly higher in patients than controls. The area under the receiver-operating characteristic (ROC) curve (AUC) was 0.85, and the optimal sensitivity and specificity for ESCC detection were 80.6 and 78.7%, respectively. LY6K mRNA expressions in patients were upregulated. CONCLUSIONS: Autoantibodies against LY6K may be a good diagnostic biomarker for ESCC.


Assuntos
Anticorpos Antineoplásicos/sangue , Antígenos Ly/imunologia , Antígenos de Neoplasias/imunologia , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Esofágicas/sangue , Adulto , Idoso , Antígenos Ly/genética , Antígenos Ly/metabolismo , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Área Sob a Curva , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/imunologia , Estudos de Casos e Controles , Clonagem Molecular , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/imunologia , Feminino , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/imunologia , Proteínas Ligadas por GPI/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Transcrição Gênica , Regulação para Cima
7.
Innovations (Phila) ; 17(2): 127-135, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35341368

RESUMO

Objective: Our objective was to evaluate for any changes in quality or cost when robotic lung resection is used with significant trainee participation. Methods: All anatomic lung resections between January 2006 and June 2016 were identified from a prospectively maintained database. Clinical data were recorded by double entry. Cost and cancer-related data were gathered from the business analytics department and tumor registry. Robotic outcomes were compared to an ongoing thoracotomy and video-assisted thoracic surgery (VATS) experience. Propensity scores using age, sex, and comorbidities were assigned for statistical analysis. Survival was evaluated using the Kaplan-Meier method. Results: Of 523 consecutive cases, 483 were included (211 robotic, 210 thoracotomy, 62 VATS). There were 74 robotic cases (35%) performed by trainees as the console surgeon. Length of stay was shortest for robotics (3 days) compared to thoracotomy (7 days, P < 0.001) and VATS (5 days, P = 0.010). Complications occurred in 33% of robotic cases, 42% of VATS cases (P = 0.854), and 52% of thoracotomy cases (P < 0.001). Stage I non-small cell lung cancer 3-year overall survival for robotics, thoracotomy, and VATS was 79.5%, 74.3%, and 74.0%, respectively (P > 0.25). There was no significant difference in negative margin rates. Total cost related to the hospitalization for surgery was $5,721 less for robotics compared to thoracotomy (P = 0.003) but comparable to VATS. Trainees served as console surgeon in 0% of cases in the first 2 years of robotics but increased to 79% in the last year of the study. Conclusions: Robotic lung resection can be safely performed and taught in an academic medical center without sacrificing quality or cost.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Análise Custo-Benefício , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida/métodos , Toracotomia , Resultado do Tratamento
8.
Thorac Surg Clin ; 21(1): 69-83, vii, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21070988

RESUMO

Thymectomy for thymoma has traditionally been performed through a transsternal approach because of the excellent exposure that that the median sternotomy provides. Minimally invasive alternatives, such as transcervical thymectomy, video-assisted thymectomy, and robotic thymectomy, have not been extensively evaluated for this disease process. It is uncertain which patients may benefit from minimally invasive approaches and data regarding the oncologic effectiveness of these techniques remains to be established. However, given the excellent capability of these techniques to perform a complete and extensive thymectomy, there does appear to be a role for minimally invasive thymectomy in the treatment of thymoma.


Assuntos
Robótica/métodos , Timectomia/métodos , Timoma/cirurgia , Neoplasias do Timo/cirurgia , Humanos , Cisto Mediastínico/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Miastenia Gravis/diagnóstico , Miastenia Gravis/epidemiologia , Miastenia Gravis/terapia , Invasividade Neoplásica , Cirurgia Torácica Vídeoassistida , Timoma/epidemiologia , Timo/anatomia & histologia , Neoplasias do Timo/epidemiologia , Neoplasias do Timo/patologia
9.
Proc Natl Acad Sci U S A ; 105(1): 252-7, 2008 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-18162535

RESUMO

Changes in DNA methylation patterns are an important characteristic of human cancer. Tumors have reduced levels of genomic DNA methylation and contain hypermethylated CpG islands, but the full extent and sequence context of DNA hypomethylation and hypermethylation is unknown. Here, we used methylated CpG island recovery assay-assisted high-resolution genomic tiling and CpG island arrays to analyze methylation patterns in lung squamous cell carcinomas and matched normal lung tissue. Normal tissues from different individuals showed overall very similar DNA methylation patterns. Each tumor contained several hundred hypermethylated CpG islands. We identified and confirmed 11 CpG islands that were methylated in 80-100% of the SCC tumors, and many hold promise as effective biomarkers for early detection of lung cancer. In addition, we find that extensive DNA hypomethylation in tumors occurs specifically at repetitive sequences, including short and long interspersed nuclear elements and LTR elements, segmental duplications, and subtelomeric regions, but single-copy sequences rarely become demethylated. The results are consistent with a specific defect in methylation of repetitive DNA sequences in human cancer.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Mapeamento Cromossômico , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/metabolismo , Biomarcadores Tumorais , Carcinoma de Células Escamosas/genética , Ilhas de CpG , DNA/metabolismo , Humanos , Neoplasias Pulmonares/genética , Modelos Genéticos , Sequências Repetitivas de Ácido Nucleico , Análise de Sequência de DNA
10.
BMC Biotechnol ; 10: 12, 2010 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-20158905

RESUMO

BACKGROUND: Veterinary drugs such as clenbuterol (CL) and sulfamethazine (SM2) are low molecular weight (<1000 Da) compounds, or haptens, that are difficult to develop immunoassays due to their low immunogenicity. In this study, we conjugated the drugs to ovalbumin to increase their immunogenicity for antiserum production in rabbits and developed a protein microarray immunoassay for detection of clenbuterol and sulfamethazine. The sensitivity of this approach was then compared to traditional ELISA technique. RESULTS: The artificial antigens were spotted on microarray slides. Standard concentrations of the compounds were added to compete with the spotted antigens for binding to the antisera to determine the IC50. Our microarray assay showed the IC50 were 39.6 ng/ml for CL and 48.8 ng/ml for SM2, while the traditional competitive indirect-ELISA (ci-ELISA) showed the IC50 were 190.7 ng/ml for CL and 156.7 ng/ml for SM2. We further validated the two methods with CL fortified chicken muscle tissues, and the protein microarray assay showed 90% recovery while the ci-ELISA had 76% recovery rate. When tested with CL-fed chicken muscle tissues, the protein microarray assay had higher sensitivity (0.9 ng/g) than the ci-ELISA (0.1 ng/g) for detection of CL residues. CONCLUSIONS: The protein microarrays showed 4.5 and 3.5 times lower IC50 than the ci-ELISA detection for CL and SM2, respectively, suggesting that immunodetection of small molecules with protein microarray is a better approach than the traditional ELISA technique.


Assuntos
Clembuterol/análise , Resíduos de Drogas/análise , Análise Serial de Proteínas/métodos , Sulfametazina/análise , Animais , Galinhas , Ensaio de Imunoadsorção Enzimática , Concentração Inibidora 50 , Músculo Esquelético/química , Ovalbumina/química , Coelhos , Sensibilidade e Especificidade , Drogas Veterinárias/análise
11.
PLoS One ; 15(4): e0231258, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32271810

RESUMO

INTRODUCTION: Advances in surgical techniques have improved clinical outcomes and decreased complications. At the same time, heightened attention to care quality has resulted in increased identification of hospital-acquired adverse events. We evaluated these divergent effects on the reported safety of lung cancer resection. METHODS AND MATERIALS: We analyzed hospital-acquired adverse events in patients undergoing lung cancer resection using the National Hospital Discharge Survey (NHDS) database from 2001-2010. Demographics, diagnoses, and procedures data were abstracted using ICD-9 codes. We used the Agency for Healthcare Research and Quality (AHRQ) Patient Safety Indicators (PSI) to identify hospital-acquired adverse events. Weighted analyses were performed using t-tests and chi-square. RESULTS: A total of 302,444 hospitalizations for lung cancer resection and were included in the analysis. Incidence of PSI increased over time (28% in 2001-2002 vs 34% in 2009-2010; P<0.001). Those with one or more PSI had increased in-hospital mortality (aOR = 11.1; 95% CI, 4.7-26.1; P<0.001) and prolonged hospitalization (12.5 vs 7.8 days; P<0.001). However, among those with PSI, in-hospital mortality decreased over time, from 17% in 2001-2002 to 2% in 2009-2010. CONCLUSIONS: In a recent ten-year period, documented rates of adverse events associated with lung cancer resection increased. Despite this increase in safety events, we observed that mortality decreased. Because such metrics may be incorporated into hospital rankings and reimbursement considerations, adverse event coding consistency and content merit further evaluation.


Assuntos
Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Qualidade da Assistência à Saúde , Relatório de Pesquisa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Fatores de Tempo , Adulto Jovem
12.
Cancer Med ; 9(12): 4137-4147, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32319225

RESUMO

BACKGROUND: Clinical outcomes for resected early-stage non-small cell lung cancer (NSCLC) are superior at high-volume facilities, but reasons for these differences remain unclear. Understanding these differences and optimizing outcomes across institutions are critical to the management of the increasing incidence of these cases. We evaluated the extent to which surgical best practices account for resected early-stage NSCLC outcome differences between facilities according to case volume. METHODS: We performed a retrospective cohort study for clinical stage 1 or 2 NSCLC undergoing surgical resection from 2004 to 2013 using the National Cancer Database (NCDB). Surgical best practices (negative surgical margins, lobar or greater resection, lymph node (LN) dissection, and examination of > 10 LNs) were compared between the highest and lowest quartile volumes. RESULTS: A total of 150,179 patients were included in the cohort (89% white, 53% female, median age 68 years). In a multivariate model, superior overall survival (OS) was observed at highest volume centers compared to lowest volume centers (hazard ratio (HR) = 0.89; 95% CI, 0.82-0.96; P = .002). After matching for surgical best practices, there was no significant OS difference (HR = 0.95; 95% CI, 0.87-1.05; P = .32). Propensity score-adjusted HR estimates indicated that surgical best practices accounted for 54% of the numerical OS difference between low-volume and high-volume centers. Each surgical best practice was independently associated with improved OS (all P ≤ .001). CONCLUSION: Quantifiable and potentially modifiable surgical best practices largely account for resected early-stage NSCLC outcome differences observed between low- and high-volume centers. Adherence to these guidelines may reduce and potentially eliminate these differences.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Hospitais com Baixo Volume de Atendimentos/estatística & dados numéricos , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo/mortalidade , Pneumonectomia/mortalidade , Padrões de Prática Médica/normas , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
13.
Ann Thorac Surg ; 109(4): 1019-1025, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31846640

RESUMO

BACKGROUND: In non-small cell lung cancer (NSCLC), 18fluoro-2-deoxyglucose-positron emission tomography (FDG-PET) assists in diagnosis, staging, and evaluating treatment response. One variable of FDG-PET, the maximum standard uptake value (SUVm), is considered an objective measure of glucose uptake. However, little is known about the fate of glucose in FDG-avid lung tumors in vivo. This study used stable glucose isotope tracing to determine whether the SUVm predicts glycolytic metabolism or other glucose fates in tumors. METHODS: In this prospective Institutional Review Board-approved clinical trial, 52 untreated potentially resectable confirmed NSCLC patients underwent FDG-PET computed tomography. During the surgical procedure, the patients were infused with 13C-labeled glucose. Blood, tumor, and normal lung samples were analyzed by mass spectrometry to determine 13C enrichment in glycolytic intermediates. These values were compared with clinical variables, including SUVm, maximum tumor diameter, stage, grade, and MIB-1/Ki67 proliferation index. RESULTS: For each patient, 13C enrichment in each metabolite was compared between tumor and adjacent lung. Although all tumors metabolized glucose, SUVm did not correlate with glycolytic intermediate labeling. Rather, SUVm correlated with markers indicating the use of other respiratory substrates, including lactate, and with the proliferation index. CONCLUSIONS: SUVm does not correlate with glycolytic metabolism in human NSCLC but does correlate with the proliferation index, suggesting that SUVm predicts glucose use by pathways other than glycolysis. These pathways may offer alternative therapeutic targets, including biosynthetic pathways required for cell proliferation. The research techniques in this study offer the opportunity to understand the relationships between SUVm, tumor metabolism, and therapeutic vulnerabilities in human NSCLCs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Glicólise/fisiologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/terapia , Feminino , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Estudos Prospectivos , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X
14.
Clin Cancer Res ; 26(22): 6017-6027, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-32847935

RESUMO

PURPOSE: Itraconazole has been repurposed as an anticancer therapeutic agent for multiple malignancies. In preclinical models, itraconazole has antiangiogenic properties and inhibits Hedgehog pathway activity. We performed a window-of-opportunity trial to determine the biologic effects of itraconazole in human patients. EXPERIMENTAL DESIGN: Patients with non-small cell lung cancer (NSCLC) who had planned for surgical resection were administered with itraconazole 300 mg orally twice daily for 10-14 days. Patients underwent dynamic contrast-enhanced MRI and plasma collection for pharmacokinetic and pharmacodynamic analyses. Tissues from pretreatment biopsy, surgical resection, and skin biopsies were analyzed for itraconazole and hydroxyitraconazole concentration, and vascular and Hedgehog pathway biomarkers. RESULTS: Thirteen patients were enrolled in this study. Itraconazole was well-tolerated. Steady-state plasma concentrations of itraconazole and hydroxyitraconazole demonstrated a 6-fold difference across patients. Tumor itraconazole concentrations trended with and exceeded those of plasma. Greater itraconazole levels were significantly and meaningfully associated with reduction in tumor volume (Spearman correlation, -0.71; P = 0.05) and tumor perfusion (Ktrans; Spearman correlation, -0.71; P = 0.01), decrease in the proangiogenic cytokines IL1b (Spearman correlation, -0.73; P = 0.01) and GM-CSF (Spearman correlation, -1.00; P < 0.001), and reduction in tumor microvessel density (Spearman correlation, -0.69; P = 0.03). Itraconazole-treated tumors also demonstrated distinct metabolic profiles. Itraconazole treatment did not alter transcription of GLI1 and PTCH1 mRNA. Patient size, renal function, and hepatic function did not predict itraconazole concentrations. CONCLUSIONS: Itraconazole demonstrates concentration-dependent early antivascular, metabolic, and antitumor effects in patients with NSCLC. As the number of fixed dose cancer therapies increases, attention to interpatient pharmacokinetics and pharmacodynamics differences may be warranted.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Itraconazol/administração & dosagem , Neovascularização Patológica/tratamento farmacológico , Adulto , Inibidores da Angiogênese/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Biópsia , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Proteínas Hedgehog/genética , Humanos , Itraconazol/análogos & derivados , Itraconazol/sangue , Itraconazol/farmacocinética , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/sangue , Neovascularização Patológica/diagnóstico por imagem , Neovascularização Patológica/cirurgia , Receptor Patched-1/genética , Proteína GLI1 em Dedos de Zinco/genética
15.
Mol Cancer Res ; 6(11): 1710-7, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19010819

RESUMO

Flap endonuclease 1 (FEN1) is a structure-specific nuclease best known for its critical roles in Okazaki fragment maturation, DNA repair, and apoptosis-induced DNA fragmentation. Functional deficiencies in FEN1, in the forms of somatic mutations and polymorphisms, have recently been shown to lead to autoimmunity, chronic inflammation, and predisposition to and progression of cancer. To explore how FEN1 contributes to cancer progression, we examined FEN1 expression using 241 matched pairs of cancer and corresponding normal tissues on a gene expression profiling array and validated differential expression by quantitative real-time PCR and immunohistochemistry. Furthermore, we defined the minimum promoter of human FEN1 and examined the methylation statuses of the 5' region of the gene in paired breast cancer tissues. We show that FEN1 is significantly up-regulated in multiple cancers and the aberrant expression of FEN1 is associated with hypomethylation of the CpG island within the FEN1 promoter in tumor cells. The overexpression and promoter hypomethylation of FEN1 may serve as biomarkers for monitoring the progression of cancers.


Assuntos
Neoplasias da Mama/genética , Metilação de DNA , Endonucleases Flap/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias/genética , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/metabolismo , Ilhas de CpG , Progressão da Doença , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Imuno-Histoquímica/métodos , Neoplasias/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos
16.
J Surg Oncol ; 100(2): 127-32, 2009 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-19544364

RESUMO

BACKGROUND: Using a large data set, we investigated the impact of the number of resected and involved lymph nodes on overall survival for patients with esophageal cancer. METHODS: From the National Oncology Database, esophageal cancer cases with data available on the total number of resected and involved nodes as well as other variables were evaluated as it relates to overall survival by multivariate analysis using Cox proportional hazards method. Patients with 0, exactly 1 or 1-3 positive nodes were separately studied to determine the association between the number of lymph nodes resected and overall survival. RESULTS: From 1969 to 2002, 3,144 (17%) of 18,390 esophageal cancer cases with complete data were identified. Increasing number of involved nodes predicted poorer outcome (P < 10(-6)). Results from studying patients with 0, exactly 1 or 1-3 positive nodes showed that survival improved with increasing number of nodes analyzed up to 12. Three-tier nodal grouping with increasing risk of death were identified, 0, 1-3, and >or=4 positive nodes (P < 10(-5)). CONCLUSIONS: The pathological assessment of minimal 12 lymph nodes provides sufficient prognostic information. Three-tier nodal grouping is suggested for the next version of AJCC staging system for esophageal cancer.


Assuntos
Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Excisão de Linfonodo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/mortalidade , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais
17.
Breast Cancer Res ; 10(3): R40, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18460216

RESUMO

INTRODUCTION: Only a limited number of tumor markers for breast cancer are currently available. Antibodies to tumor-associated proteins may expand the number of available tumor markers for breast cancer and may be used together in a serum profile to enhance sensitivity and specificity. METHODS: In the present study, we interrogated a breast cancer cDNA T7 phage library for tumor-associated proteins using biopan enrichment techniques with sera from normal individuals and from breast cancer patients. The enrichment of tumor-associated proteins after biopanning was tested using a plaque-lift assay and immunochemical detection. The putative tumor-associated phage clones were collected for PCR and sequencing analysis. Unique and open reading frame phage-expressed proteins were then used to develop phage protein ELISAs to measure corresponding autoantibodies using 87 breast cancer patients and 87 normal serum samples. A logistic regression model and leave-one-out validation were used to evaluate predictive accuracies with a single marker as well as with combined markers. Identities of those selected proteins were revealed through the sequence BLAST program. RESULTS: We harvested 100 putative tumor-associated phage clones after biopan enrichment. Sequencing analysis revealed that six phage proteins were inframe and unique. Antibodies to these six phage-expressed proteins were measured by ELISAs, and the results showed that three of the phage clones had statistical significance in discriminating patients from normal individuals. BLAST results of the three proteins showed great matches to ASB-9, SERAC1, and RELT. Measurements of the three predictive phage proteins were combined in a logistic regression model that achieved 80% sensitivity and 100% specificity in prediction of sample status, whereas leave-one-out validation achieved 77.0% sensitivity and 82.8% specificity among 87 patient samples and 87 control samples. Receiver operating characteristic curve analysis and the leave-one-out method both showed that combined measurements of the three antibodies were more predictive of disease than any of the single antibodies studied, underscoring the importance of identifying multiple potential markers. CONCLUSION: Serum autoantibody profiling is a promising approach for early detection and diagnosis of breast cancer. Rather than one autoantibody, a panel of autoantibodies appears preferable to achieve superior accuracy. Further refinements will need to be made to further improve the accuracy. Once refined, the assay must be applied to a prospective patient population to demonstrate applicability.


Assuntos
Autoanticorpos/biossíntese , Autoanticorpos/sangue , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Estadiamento de Neoplasias/métodos , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/imunologia , Autoanticorpos/genética , Autoanticorpos/imunologia , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Biblioteca Gênica , Humanos , Fases de Leitura Aberta , Reação em Cadeia da Polimerase , Reprodutibilidade dos Testes
18.
Semin Thorac Cardiovasc Surg ; 20(4): 326-31, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19251172

RESUMO

Thymectomy is an established therapy for myasthenia gravis. Minimally invasive surgery for thymectomy has been reported, but not clearly shown to be equivalent to open resection. Robotic-assisted thymectomy may provide the benefit of a full resection of thymic tissue and anterior mediastinal tissue for the treatment of myasthenia gravis by a minimally invasive approach. We present a review of the experience of robotic thymectomy.


Assuntos
Miastenia Gravis/cirurgia , Robótica/métodos , Timectomia/métodos , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos , Complicações Pós-Operatórias
19.
Innovations (Phila) ; 13(6): 391-403, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30543576

RESUMO

Great advances have been made in the surgical management of esophageal disease since the first description of esophageal resection in 1913. We are in the era of minimally invasive esophagectomy. The current three main approaches to an esophagectomy are the Ivor Lewis technique, McKeown technique, and the transhiatal approach to esophagectomy. These operations were associated with a high morbidity and mortality. The recent advances in minimally invasive surgical techniques have greatly improved the outcomes of these surgical procedures. This article reviews the literature and describes the various techniques available for performing minimally invasive esophagectomy and robot-assisted esophagectomies, the history behind the development of these techniques, the variations, and the contemporary outcomes after such procedures.


Assuntos
Esofagectomia , Procedimentos Cirúrgicos Minimamente Invasivos , Procedimentos Cirúrgicos Robóticos , Neoplasias Esofágicas/cirurgia , Humanos
20.
Int J Radiat Oncol Biol Phys ; 68(5): 1537-45, 2007 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-17531399

RESUMO

PURPOSE: To use pretreatment megavoltage computed tomography (MVCT) scans to evaluate setup variations in anterior-posterior (AP), lateral, and superior-inferior (SI) directions and rotational variations, including pitch, roll, and yaw, for esophageal cancer patients treated with helical tomotherapy. METHODS AND MATERIALS: Ten patients with locally advanced esophageal cancer treated by combined chemoradiation using helical tomotherapy were selected. After patients were positioned using their skin tattoos/marks, MVCT scans were performed before every treatment and automatically registered to planning kilovoltage CT scans according to bony landmarks. Image registration data were used to adjust patient setups before treatment. A total of 250 MVCT scans were analyzed. Correlations between setup variations and body habitus, including height, weight, relative weight change, body surface area, and patient age, were evaluated. RESULTS: The standard deviations for systematic setup corrections in AP, lateral, and SI directions and pitch, roll, and yaw rotations were 1.5, 3.7, and 4.8 mm and 0.5 degrees, 1.2 degrees, and 0.8 degrees, respectively. The appropriate averages of random setup variations in AP, lateral, and SI directions and pitch, roll, and yaw rotations were 2.9, 5.2, and 4.4 mm, and 1.0 degrees, 1.2 degrees, and 1.1 degrees, respectively. Setup variations were stable throughout the entire course of radiotherapy in all three translational and three rotational displacements, with little change in magnitude. No significant correlations were found between setup variations and body habitus variables. CONCLUSIONS: Daily MVCT scans before each treatment can effectively detect setup errors and thereby reduce planning target volume (PTV) margins. This will reduce radiation dose to critical organs and may translate into lower treatment-related toxicities.


Assuntos
Neoplasias Esofágicas/diagnóstico por imagem , Planejamento da Radioterapia Assistida por Computador/métodos , Tomografia Computadorizada Espiral , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Tamanho Corporal , Superfície Corporal , Neoplasias Esofágicas/radioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radioterapia Conformacional , Estudos Retrospectivos
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