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1.
J Thorac Dis ; 16(3): 1875-1884, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38617767

RESUMO

Background: Long-standing controversy has existed over whether sublobar resection is an adequate oncological procedure for clinical stage IA non-small cell lung cancer (NSCLC) ≤2 cm, despite the recent randomized trial reports of Japanese Clinical Oncology Group (JCOG) 0802 and Cancer and Leukemia Group B (CALGB) 140503 demonstrating non-inferior outcomes with sublobar resection compared to lobectomy. As practice patterns shift, we sought to compare oncologic outcomes in patients with these early-stage tumors after wedge resection, segmentectomy, or lobectomy in a contemporary, real-world, cohort. Methods: A retrospective review of a prospectively maintained database from a single institution was conducted from 2011 to 2020 to identify all patients with clinically staged IA1 or IA2 NSCLC (tumors ≤2 cm with no nodal involvement). The primary outcomes of interest were overall survival (OS) and disease-free survival (DFS), with secondary outcomes of lung cancer-specific survival (LCSS), recurrence patterns, and perioperative morbidity and mortality. Results: A total of 480 patients were identified; 93 (19.4%) patients underwent wedge resection, 90 (18.7%) received segmentectomy, and 297 (61.9%) underwent lobectomy. Patients who underwent wedge resection had worse Eastern Cooperative Oncology Group (ECOG) performance status (23.7% ECOG 1 or 2 vs. 5.6% among segmentectomy and 5.4% among lobectomy, P<0.05). Both wedge resection and segmentectomy patients had lower preoperative mean percentage of predicted forced expiratory volume in one second (%FEV1) compared to the lobectomy group (81.8% and 82.6% vs. 89.6%, P=0.002), a higher proportion of patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD), and a higher Charlson Comorbidity Index. There were no statistically significant differences in 5-year OS, DFS, or LCSS between groups: 90%, 61%, 78% for wedge resections compared with 85%, 75%, 86% for segmentectomy, and 87%, 77%, 87% for lobectomy, respectively. Recurrence was observed in 17 patients who underwent wedge resection (18.3%, 8 local, 9 distant), 12 patients who received segmentectomy (13.4%, 6 local, 6 distant), and 38 patients who underwent lobectomy (12.8%, 11 local, 27 distant), which was not significantly different (P=0.36). Conclusions: Patients with inferior performance status or lower baseline pulmonary function are more likely to receive wedge resection for clinical stage IA NSCLC ≤2 cm in size. For these small tumors, lobectomy, segmentectomy, and wedge resection provide comparable oncologic outcomes.

2.
Environ Res ; 247: 118193, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38220086

RESUMO

In the presented study, a novel polypyrrole-decorated bentonite magnetic nanocomposite (MBnPPy) was synthesized for efficient removal of both anionic methyl orange (MO) and cationic crystal violet (CV) dyes from contaminated water. The synthesis of this novel adsorbent involved a two-step process: the magnetization of bentonite followed by its modification through in-situ chemical polymerization. The adsorbent was characterized by SEM/EDX, TEM/SAED, BET, TGA/DTA-DTG, FTIR, VSM, and XRD studies. The investigation of the adsorption properties of MBnPPy was focused on optimizing various parameters, such as dye concentration, medium pH, dosage, contact time, and temperature. The optimal conditions were established as follows: dye concentration of Co (CV/MO) at 100 mg/L, MBnPPy dosage at 2.0 g/L, equilibrium time set at 105 min for MO and 120 min for CV, medium pH adjusted to 5.0 for MO dye and 8.0 for CV dye, and a constant temperature of 303.15 K. The different kinetic and isotherm models were applied to fit the experimental results, and it was observed that the Pseudo-2nd-order kinetics and Langmuir adsorption isotherm were the best-fitted models. The maximal monolayer adsorption capacities of the adsorbent were found to be 78.74 mg/g and 98.04 mg/g (at 303.15 K) for CV and MO, respectively. The adsorption process for both dyes was exothermic and spontaneous. Furthermore, a reasonably good regeneration ability of MBnPPy (>83.45%/82.65% for CV/MO) was noted for up to 5 adsorption-desorption cycles with little degradation. The advantages of facile synthesis, cost-effectiveness, non-toxicity, strong adsorption capabilities for both anionic and cationic dyes, and easy separability with an external magnetic field make MBnPPy novel.


Assuntos
Compostos Azo , Nanocompostos , Poluentes Químicos da Água , Corantes/química , Adsorção , Polímeros , Violeta Genciana/química , Bentonita/química , Pirróis , Água/química , Fenômenos Magnéticos , Poluentes Químicos da Água/análise , Concentração de Íons de Hidrogênio , Cinética
4.
Nat Commun ; 14(1): 8435, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38114518

RESUMO

We previously reported the results of a randomized phase II trial (NCT02904954) in patients with early-stage non-small cell lung cancer (NSCLC) who were treated with either two preoperative cycles of the anti-PD-L1 antibody durvalumab alone or combined with immunomodulatory doses of stereotactic radiation (DRT). The trial met its primary endpoint of major pathological response, which was significantly higher following DRT with no new safety signals. Here, we report on the prespecified secondary endpoint of disease-free survival (DFS) regardless of treatment assignment and the prespecified exploratory analysis of DFS in each arm of the trial. DFS at 2 and 3 years across patients in both arms of the trial were 73% (95% CI: 62.1-84.5) and 65% (95% CI: 52.5-76.9) respectively. For the exploratory endpoint of DFS in each arm of the trial, three-year DFS was 63% (95% CI: 46.0-80.4) in the durvalumab monotherapy arm compared to 67% (95% CI: 49.6-83.4) in the dual therapy arm. In addition, we report post hoc exploratory analysis of progression-free survival as well as molecular correlates of response and recurrence through high-plex immunophenotyping of sequentially collected peripheral blood and gene expression profiles from resected tumors in both treatment arms. Together, our results contribute to the evolving landscape of neoadjuvant treatment regimens for NSCLC and identify easily measurable potential biomarkers of response and recurrence.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Terapia Neoadjuvante , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Fase II como Assunto
5.
Artigo em Inglês | MEDLINE | ID: mdl-37926198

RESUMO

OBJECTIVE: In 2022, the American College of Surgeons Commission on Cancer issued standard 5.8 quality metric for curative lung cancer resections requiring nodal resection from 3 N2 stations. In this report, we compare oncologic outcomes after resection of 3 N2 stations versus 2 N2 stations in stage I non-small cell lung cancer. METHODS: A retrospective review from a single institution database was conducted from 2011 to 2020 to identify patients with clinical stage I non-small cell lung cancer. Patients with a history of lung cancer, carcinoid tumors, and ground-glass lesions less than 50% solid component were excluded. The primary outcome was overall survival. Secondary outcomes included disease-free survival, recurrence patterns, and nodal upstaging. RESULTS: A total of 581 patients were identified and divided into 2 groups based on the number of N2 stations examined: Group A had 2 N2 stations examined (364 patients), and group B had 3 or more N2 stations examined (217 patients). Baseline demographic and clinical characteristics were similar between groups. In group A, N1 and N2 positive nodal stations were present in 8.2% (30/364) and 5.2% (19/364) of patients versus 7.4% (16/217) and 5.5% (12/217), respectively, in group B. Five-year overall survival and disease-free survival were 89% and 74% in group A versus 88% and 78% in group B, respectively. Recurrence occurred in 56 patients (15.4%) in group A (6.6% local and 8.8% distant) and 29 patients (13.4%) in group B (5.1% local and 8.3% distant; P = .73). CONCLUSIONS: There was no significant difference in oncological outcomes in stage I non-small cell lung cancer resections that included 2 N2 stations compared with at least 3 N2 stations examined.

6.
Heliyon ; 9(8): e18400, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37520962

RESUMO

Objective: Since motor nerve conduction slowing can occur due to loss of large axons, we investigate the conduction slowing profile in amyotrophic lateral sclerosis (ALS) and identify the limits beyond which the diagnosis of exclusive axonal loss is unlikely. Methods: First, using linear regression analysis, we established the range of motor conduction slowing in 76 chronic inflammatory demyelinating polyneuropathy (CIDP) patients. Demyelinating range confidence intervals were defined by assessing conduction velocity (CV), distal latency (DML), and F-wave latency (F) in relation to distal compound muscle action potential (CMAP) amplitude of median, ulnar, fibular, and tibial nerves. Results were subsequently validated in 38 additional CIDP patients. Then, the newly established demyelination confidence intervals were used to investigate the profile of conduction slowing in 95 ALS patients. Results: CV slowing, prolonged DML, and abnormal F were observed in 22.2%, 19.6%, and 47.1% of the studied nerves respectively in ALS patients. When slowing occurred, it affected more than one segment of the motor nerve, suggesting that CMAP amplitude dependent conduction slowing caused by an exclusive loss of large axons is the main mechanism of slowing. No ALS patient had more than 2 nerves with CV slowing in the confidence interval defined by the regression equations or the American Academy of Neurology (AAN) research criteria for CIDP diagnosis. Conclusions: The presence of more than two motor nerves with CV slowing in the demyelinating range defined by the regression analysis or AAN criteria in ALS patients suggests the contribution of acquired demyelination or other additional mechanisms exist in the electrodiagnostic profile of ALS.

7.
Ann Surg ; 278(1): e43-e50, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35866662

RESUMO

OBJECTIVE: The aim was to determine the prevalence of metastases to the cervical and recurrent laryngeal cervicothoracic (CT) nodes as well as survival and recurrence patterns after esophagectomy with three-field lymph node dissection (TFD) in patients with predominately adenocarcinoma (AC) of the esophagus. BACKGROUND: Although esophagectomy with TFD is commonly practiced in Japan and Southeast Asia for squamous cell cancer (SCC) of the esophagus, there are only a handful of reports about its' utilization and survival benefit in North American patients. METHODS: This is a retrospective case series of patients who had an esophagectomy with TFD. The primary outcomes of interest were the prevalence of nodal metastases to the CT nodes as well as overall survival (OS) and disease-free survival. Secondary outcomes included time to recurrence, recurrence patterns, operative morbidity as well as 30 and 90-day mortality. RESULTS: Two hundred forty-two patients with esophageal cancer (AC: 67%) underwent esophagectomy with TFD. Metastases to the CT nodes were present in 56 patients (23%: AC 20% and SCC 30%). Positive CT nodes were present in 14% of pT1/T2 tumors and 30% of pT3 tumors. For the 56 patients with CT positive nodes, 5-year OS was 25% (AC:16%; SCC:39%). Fifteen of 56 (26.7%) patients with metastases to the CT nodes were alive and disease-free at a minimum of 5 years postoperatively. Ten-year OS was 43% for all patients with SCC and 28% for patients with AC. CONCLUSIONS: Metastases to the CT nodes are common in both SCC and AC of the esophagus and may be present in at least 14% of early lesions. Five-year survival is encouraging particularly for patients with esophageal SCC cancer.


Assuntos
Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Estudos Retrospectivos , Estadiamento de Neoplasias , Excisão de Linfonodo , Carcinoma de Células Escamosas do Esôfago/cirurgia , Carcinoma de Células Escamosas do Esôfago/patologia , Células Epiteliais , Esofagectomia , Linfonodos/patologia
8.
J Thorac Cardiovasc Surg ; 165(1): 327-334.e2, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36028357

RESUMO

OBJECTIVE: Several trials have recently reported the safety of pulmonary resection after neoadjuvant immunotherapy with encouraging major pathological response rates. We report the detailed adverse events profile from a recently conducted randomized phase II trial in patients with resectable non-small cell lung cancer treated with neoadjuvant durvalumab alone or with sub-ablative radiation. METHODS: We conducted a randomized phase II trial in patients with non-small cell lung cancer clinical stages I to IIIA who were randomly assigned to receive neoadjuvant durvalumab alone or with sub-ablative radiation (8Gyx3). Secondary end points included the safety of 2 cycles of preoperative durvalumab with and without radiation followed by pulmonary resection. Postoperative adverse events within 30 days were recorded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0). RESULTS: Sixty patients were enrolled and randomly assigned, with planned resection performed in 26 patients in each arm. Baseline demographics and clinical variables were balanced between groups. The median operative time was similar between arms: 128 minutes (97-201) versus 146 minutes (109-214) (P = .314). There was no 30- or 90-day mortality. Grade 3/4 adverse events occurred in 10 of 26 patients (38%) after monotherapy and in 10 of 26 patients (38%) after dual therapy. Anemia requiring transfusion and hypotension were the 2 most common adverse events. The median length of stay was similar between arms (5 days vs 4 days, P = .172). CONCLUSIONS: In this randomized trial, the addition of sub-ablative focal radiation to durvalumab in the neoadjuvant setting was not associated with increased mortality or morbidity compared with neoadjuvant durvalumab alone.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
9.
J Thorac Cardiovasc Surg ; 164(2): 378-385, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35459540

RESUMO

BACKGROUND: The influence of SARS-CoV-2 on surgery for non-small cell lung cancer needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. OBJECTIVE: This study reports on the 90-day rate of infection as well as the morbidity and mortality of lung surgery for cancer in a tertiary care hospital located in a pandemic epicenter. METHODS: We conducted a retrospective review of a prospective database to identify consecutive patients who underwent lung cancer resection before (January 1, 2020-March 10, 2020, group 1; 57 patients) and during the COVID-19 pandemic (March 11, 2020-June 10, 2020, group 2; 41 patients). The primary end point was the occurrence of SARS-CoV-2 infection during the first 90-days after surgery. The secondary outcome measure was 90-day perioperative morbidity and mortality. RESULTS: Patient characteristics were not significantly different between the groups. Ninety-day COVID-19 infection rates was 7.3% (3 out of 41) for patients undergoing an operation during the pandemic and 3.5% (2 out of 57) in patients operated on immediately before the pandemic. All patients tested positive 10 to 62 days after the index surgical procedure following hospital discharge. Four COVID-19-positive patients were symptomatic and 4 out of 5 patients required hospitalization, were men, previous or current smokers with hyperlipidemia, and underwent a sublobar resection. Univariate analysis did not identify any differences in postoperative complications before or during the COVID-19 pandemic. Ninety-day mortality was 5% (2 out of 41) for lung cancer surgery performed during the pandemic, with all deaths occurring due to COVID-19, compared with 0% (0 out of 57) mortality in patients who underwent an operation before the pandemic. CONCLUSIONS: During the COVID-19 pandemic, COVID-19 infections occurred in 7.3% of patients who underwent surgery for non-small cell lung cancer. In this series all infections occurred after hospital discharge. Our results suggest that COVID-19 infections occurring within 90 days of surgery portend a 40% mortality, warranting close postoperative surveillance.


Assuntos
COVID-19 , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , COVID-19/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/cirurgia , Masculino , Pandemias , Estudos Retrospectivos , SARS-CoV-2
10.
Sci Transl Med ; 14(636): eabe8195, 2022 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-35294260

RESUMO

Most patients with non-small cell lung cancer (NSCLC) do not achieve durable clinical responses from immune checkpoint inhibitors, suggesting the existence of additional resistance mechanisms. Nicotinamide adenine dinucleotide (NAD)-induced cell death (NICD) of P2X7 receptor (P2X7R)-expressing T cells regulates immune homeostasis in inflamed tissues. This process is mediated by mono-adenosine 5'-diphosphate (ADP)-ribosyltransferases (ARTs). We found an association between membranous expression of ART1 on tumor cells and reduced CD8 T cell infiltration. Specifically, we observed a reduction in the P2X7R+ CD8 T cell subset in human lung adenocarcinomas. In vitro, P2X7R+ CD8 T cells were susceptible to ART1-mediated ADP-ribosylation and NICD, which was exacerbated upon blockade of the NAD+-degrading ADP-ribosyl cyclase CD38. Last, in murine NSCLC and melanoma models, we demonstrate that genetic and antibody-mediated ART1 inhibition slowed tumor growth in a CD8 T cell-dependent manner. This was associated with increased infiltration of activated P2X7R+CD8 T cells into tumors. In conclusion, we describe ART1-mediated NICD as a mechanism of immune resistance in NSCLC and provide preclinical evidence that antibody-mediated targeting of ART1 can improve tumor control, supporting pursuit of this approach in clinical studies.


Assuntos
ADP Ribose Transferases , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Subpopulações de Linfócitos T , ADP Ribose Transferases/genética , ADP Ribose Transferases/metabolismo , Difosfato de Adenosina , Animais , Carcinoma Pulmonar de Células não Pequenas/imunologia , Proteínas Ligadas por GPI/genética , Humanos , Neoplasias Pulmonares/imunologia , Camundongos
11.
Ann Thorac Surg ; 114(3): 959-967, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35181271

RESUMO

BACKGROUND: Minimal literature exists evaluating the impact of the extent of resection on survival in patients with small, early-stage non-small cell lung cancer (NSCLC) found to have occult nodal disease. We hypothesized that sublobar resection has comparable overall survival to patients undergoing lobectomy for clinical stage IA NSCLC that harbors occult nodal disease. METHODS: The National Cancer Database was reviewed for identification of patients with clinical stage IA NSCLC who underwent wedge resection, segmentectomy, or lobectomy and were found to have occult nodal disease. Overall survival was compared between groups, and a multivariate Cox regression model identified factors associated with worse survival. RESULTS: Occult nodal disease occurred in 6.1% of all patients with clinical stage IA disease undergoing resection. Patients undergoing wedge resection and segmentectomy found to have occult nodal disease were older (67.6 ± 9.6 years of age vs 66.1 ± 9.3 years of age vs 65.6 ± 9.5 years of age; P = .004) and had more advanced pathologic stage (pStage III: 68.7% vs 50.5% vs 41.5%; P < .001) than those receiving lobectomy. There was no difference in the median overall survival between segmentectomy and lobectomy (68.5 months vs 57.6 months; P = .200). However, wedge resection was independently associated with worse overall survival when controlling for other preoperative variables (hazard ratio, 1.23; 95% confidence interval, 1.01-1.51; P = .042). CONCLUSIONS: Review of the National Cancer Database suggests that there is no improvement in overall survival in patients undergoing lobectomy vs segmentectomy in carefully selected patients with clinical stage IA NSCLC harboring occult nodal disease. However, those undergoing wedge resection may have worse overall survival than those undergoing both lobectomy and segmentectomy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Idoso , Humanos , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonectomia , Modelos de Riscos Proporcionais , Estudos Retrospectivos
12.
Ann Thorac Surg ; 114(3): 905-910, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-34454901

RESUMO

BACKGROUND: Routine mutation profiling for resected lung cancers is not widespread despite an increasing array of targeted therapies. We report the incidence of epidermal growth factor receptor mutations (EGFRmu+) in resected lung adenocarcinomas and their outcomes at a large North American cancer center to characterize this population now eligible for targeted adjuvant therapy. METHODS: Among 1036 pulmonary resections performed between 2015 and 2019, 647 patients (62%) had adenocarcinomas that underwent molecular profiling by next-generation sequencing. Clinical and pathologic characteristics, along with survival, were analyzed. RESULTS: EGFRmu+ were identified in 238 patients (37%). Patients with EGFRmu+ were more likely to be Asian than those with EGFR wild-type (79/238 [33%] vs 37/409 [9%], respectively; P < .001) and more likely to be never-smokers (115/238 [48%] vs 73/409 [18%], P < .001). However, most patients with EGFRmu+ in our cohort were White (45%) and had a history of smoking (52%). A statistically nonsignificant trend was observed toward improved 3-year overall survival for pathologic stage IB to III cancers with EGFRmu+ (91% vs 77%, P = .09). Patients with pathologic stage IB lung cancers with EGFRmu+ had a 97% rate of 3-year disease-free survival, with only 1 recurrence in the first 3 years of follow-up. EGFR mutation subtype was not associated with survival differences. CONCLUSIONS: Although Asians and never-smokers comprised a disproportionately large group of patients with lung adenocarcinomas with EGFRmu+, most EGFR mutations within our cohort were found in patients who were White or with a smoking history, supporting a routine rather than selective approach to mutation profiling. Patients with surgically resected stage IA and IB lung adenocarcinomas enjoy excellent survival regardless of their mutational status.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/cirurgia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/cirurgia , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Mutação , Estadiamento de Neoplasias
13.
J Environ Manage ; 298: 113483, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34391107

RESUMO

Ever-growing demands for energy, the unsustainability of fossil fuel due to its scarcity and massive impact on global economies and the environment, have encouraged the research on alternative power sources to work upon for the governments, companies, and scientists across the world. Enzymatic biofuel cells (eBFCs) is one category of fuel cell that can harvest energy from biological moieties and has the future to be used as an alternative source of energy. The aim of this review is to summarize the background and state-of-the-art in the field of eBFCs. This review article will be very beneficial for a wide audience including students and new researchers in the field. A part of the paper summarized the challenges in the preparation of anode and cathode and the involvement of nanomaterials and conducting polymers to construct the effective bioelectrodes. It will provide an insight for the researchers working in this challenging field. Furthermore, various applications of eBFCs in implantable power devices, tiny electronic gadgets, and self powered biosensors are reported. This review article explains the development in the area of eBFCs for several years from its origin to growth systematically. It reveals the strategies that have been taken for the improvements required for the better electrochemical performance and operational stability of eBFCs. It also mentions the challenges in this field that will require proper attention so that the eBFCs can be utilized commercially in the future. The review article is written and structurized in a way so that it can provide a decent background of eBFCs to its reader. It will definitely help in enhancing the interest of reader in eBFCs.


Assuntos
Fontes de Energia Bioelétrica , Técnicas Biossensoriais , Nanoestruturas , Eletrodos , Humanos , Polímeros
14.
Am J Pathol ; 191(9): 1638-1650, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34119472

RESUMO

Cullin (CUL) 4A and 4B ubiquitin ligases are often highly accumulated in human malignant neoplasms and are believed to possess oncogenic properties. However, the underlying mechanisms by which CUL4A and CUL4B promote pulmonary tumorigenesis remain largely elusive. This study reports that CUL4A and CUL4B are highly expressed in patients with non-small cell lung cancer (NSCLC), and their high expression is associated with disease progression, chemotherapy resistance, and poor survival in adenocarcinomas. Depletion of CUL4A (CUL4Ak/d) or CUL4B (CUL4Bk/d) leads to cell cycle arrest at G1 and loss of proliferation and viability of NSCLC cells in culture and in a lung cancer xenograft model, suggesting that CUL4A and 4B are oncoproteins required for tumor maintenance of certain NSCLCs. Mechanistically, increased accumulation of the cell cycle-dependent kinase inhibitor p21/Cip1/WAF1 was observed in lung cancer cells on CUL4 silencing. Knockdown of p21 rescued the G1 arrest of CUL4Ak/d or CUL4Bk/d NSCLC cells, and allowed proliferation to resume. These findings reveal that p21 is the primary downstream effector of lung adenocarcinoma dependence on CUL4, highlight the notion that not all substrates respond equally to abrogation of the CUL4 ubiquitin ligase in NSCLCs, and imply that CUL4Ahigh/CUL4Bhigh may serve as a prognostic marker and therapeutic target for patients with NSCLC.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Proteínas Culina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Neoplasias Pulmonares/metabolismo , Adenocarcinoma de Pulmão/patologia , Animais , Biomarcadores/metabolismo , Proliferação de Células , Sobrevivência Celular , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/fisiologia , Feminino , Xenoenxertos , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Prognóstico , Transdução de Sinais/fisiologia , Ubiquitina/metabolismo
15.
Int J Biol Macromol ; 161: 88-100, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32512098

RESUMO

The adsorption characteristic of polypyrrole decorated chitosan-based magsorbent (MChs/Ppy) for the elimination of cationic crystal violet and anionic methyl orange dye from wastewater were explored. The characteristics of MChs/Ppy were studied by TGA, SEM/EDAX, TEM, BET, FTIR, VSM, and XRD analyses. The performance of MChs/Ppy towards the adsorption of CV and MO was investigated by the batch method. Removal performance was obtained to be 88.11 and 92.89% for CV and MO at the optimum conditions. The adsorption of CV was well described by pseudo 2nd order, while that of MO was best followed by the pseudo 1st order kinetics. The adsorption equilibrium data for both the dyes were fitted well with Langmuir adsorption isotherm with the maximum monolayer sorption capacity of 62.89 and 89.29 mg/g for CV and MO, respectively. The negative values of ΔH and ΔF accompanying with the removal of both dyes specified the adsorption process to be exothermic and spontaneous. Regeneration study showed that MChs/Ppy could be reused efficaciously up to three consecutive ad-/de-sorption cycles. The combined benefits of facile synthesis, non-toxicity, and good adsorption potential towards cationic and anionic dyes along with easy magnetic separability make MChs/Ppy as a novel adsorbent.


Assuntos
Quitosana/química , Polímeros/síntese química , Pirróis/síntese química , Adsorção , Ânions/química , Cátions/química , Corantes/química , Concentração de Íons de Hidrogênio , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica , Poluentes Químicos da Água/química , Purificação da Água/métodos , Difração de Raios X
16.
Sci Rep ; 10(1): 10428, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32591600

RESUMO

A glassy carbon electrode (GC) immobilized with chitosan (CHI)@reduced graphene (rGO)-polyaniline (PAni)/ferritin (Frt)/glucose oxidase (GOx) bioelectrode was prepared. The prepared electrode was characterized by using cyclic voltammetry (CV), linear sweep voltammetry (LSV) and electrochemical impedance spectroscopy (EIS) techniques. The morphological characterization was made by scanning electron microsopy (SEM) and Fourier transform infrared (FTIR) spectroscopy. This bioelectrode provided a stable current response of 3.5 ± 0.02 mAcm-2 in 20 mM glucose. The coverage of enzyme on 0.07 cm2 area of electrode modified with CHI@rGO-PAni/Frt was calculated to be 3.80 × 10-8 mol cm-2.

17.
Sci Rep ; 10(1): 7983, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32409753

RESUMO

The low cost, eco-friendly and potential biomass, i.e. walnut (Juglans regia) shell powder was deployed for the removal of toxic methylene blue dye from contaminated water solution. The important characterization of the waste material was conducted by using several techniques, i.e. Scanning electron microscope, Fourier-transform infrared spectroscopy, Energy-dispersive X-ray spectroscopy, X-ray powder diffraction, Brunauer-Emmett-Teller surface area analysis, and Thermogravimetric analysis. The marked impact of various operating conditions, i.e. dose, concentration, time, pH and temperature on the adsorption process was investigated. Increasing pH resulted in an increase of percent dye adsorption, and the adsorption mechanism was occurred by electrostatic attraction between negative adsorbent surface and positive dye molecules. The equilibrium data suited with Langmuir isotherm model while the adsorption practice followed the pseudo-second-order kinetic model. Higher temperature reduced the adsorption of dye molecules. The adsorption process was spontaneous, exothermic and chemical. The critical statistical analysis of the experimental results was directed by forming the design of the experiment, which was further, optimized by ANOVA, 3D and perturbation plots. The error and predicted values of both the studied responses as derived from the statistical model showed the agreeable results. 0.1 N HCl was found to be effective in complete desorption. The results are very practical and prove the effectiveness of walnut shell powder in the usage of decolorization for methylene blue.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32279970

RESUMO

OBJECTIVE: Surgery may be underused for stage IIIA non-small cell lung cancer. Although an argument can be made for definitive chemoradiation for N2/3 mediastinal nodal disease, the role of a nonsurgical strategy is less clear in patients with cT3N1M0 stage IIIA given a lack of randomized data. We sought to determine the outcomes of patients with cT3N1M0 by treatment type from the National Cancer Database. METHODS: The National Cancer Database (2004-2014) was queried for patients with cT3N1M0 non-small cell lung cancer, known treatment modalities, and sequence. Comparisons between groups were performed using Mann-Whitney and chi-square tests. Cox regression was performed to identify predictors of overall survival. Propensity score matching analysis was performed to compare overall survival in surgery versus definitive chemoradiation. RESULTS: We identified 1937 patients undergoing surgery (1518 up-front and 419 after neoadjuvant treatment) and 1844 patients undergoing definitive chemoradiation. Among patients undergoing surgery without prior treatment, 19% were overstaged and were found to have pN0, whereas 9.6% had pN2/3. Median overall survival was 33.1 months in the surgery group (± adjuvant/neoadjuvant) versus 18 months in definitive chemoradiation. To compare outcomes in balanced groups, we propensity matched 1081 pairs of patients. Median overall survival was 31.1 months in the surgery group compared with 19.1 months in the definitive chemoradiation group (P < .001). By multivariable analysis, surgery (hazard ratio, 0.65; confidence interval, 0.59-0.73), female sex (hazard ratio, 0.88; confidence interval, 0.79-0.98), age (hazard ratio, 1.02; confidence interval, 1.01-1.03), squamous histology (hazard ratio, 1.22; confidence interval, 1.07-1.38), and Charlson score of 2 (hazard ratio, 1.31; confidence interval, 1.11-1.54) were predictors of survival. CONCLUSIONS: In the National Cancer Database, approximately half of patients with clinical T3N1M0 were treated with definitive chemoradiation rather than surgery. This practice should be avoided in operable patients, because surgical resection is associated with better survival.

19.
Ann Thorac Surg ; 109(6): 1670-1676, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32057814

RESUMO

BACKGROUND: Stapling across lung parenchyma may lead to tissue granulation, which could be confused radiographically with recurrence. We sought to define the time course and radiographic characteristics of such thickening and to determine their association with recurrence. METHODS: Patients who underwent limited resection for non-small cell lung cancer were included. Surveillance computed tomography scans were reviewed to characterize the morphology and size of staple line granulation tissue. Radiological and clinical findings were analyzed and univariate predictors of recurrence were examined. RESULTS: We characterized 78 patients for tissue granulation a total of 314 times in serial scans. On initial postoperative scans, 3.8% (n = 3) of staple lines showed no thickening and 17.9% (n = 14) showed thickening less than 2 mm, whereas 78.2% (n = 61) showed thickening 2 mm or greater. Of the 75 staple lines with thickening, soft tissue was characterized as linear in 32.0% (n = 24), focal along the pleura, hilum, or parenchyma in 24.0% (n = 18), and nodular in 44.0% (n = 33). Subsequent scans revealed that 25.3% of these areas (n = 19) did not change in shape or size over time, 58.7% (n = 44) showed regressive changes, and 16.0% (n = 12) showed progressive changes, the thickening of which in all 12 of these patients showed an increase in the largest dimension by 2 mm or greater. Among the 78 patients, 7.7% (n = 6) had biopsy-proven recurrence along the staple line. An increase in the largest dimension by 2 mm or greater (83.3% versus 9.7%; P = .001) and radiologic concern for malignancy (66.7% versus 11.1%; P = .001) predicted staple line recurrence. CONCLUSIONS: Staple line thickening is a frequent occurrence after pulmonary limited resection, but rarely indicative of recurrence. The characteristics and initial size of granulation tissue do not predict recurrence. Increases in tissue 2 mm or greater at the staple line over time predict local recurrence, which typically occurs after a prolonged time interval.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Pulmão/patologia , Pulmão/cirurgia , Pneumonectomia/métodos , Grampeamento Cirúrgico , Idoso , Feminino , Humanos , Masculino , Tecido Parenquimatoso/patologia , Tecido Parenquimatoso/cirurgia , Estudos Retrospectivos
20.
J Thorac Dis ; 11(4): 1355-1362, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31179077

RESUMO

BACKGROUND: There is a paucity of data regarding the role of wedge resection (WR) in the management of bronchial carcinoid (BC) tumors. In this study, we queried the Surveillance, Epidemiology, and End Results (SEER) database to compare the oncologic outcomes of patients with BC tumors treated with WR or anatomic resection. METHODS: The SEER database was retrospectively reviewed for patients with BC treated with surgical resection between 1973-2013. Patients who underwent WR were compared to those who underwent lobectomy or segmentectomy (Lob/Seg). Patients with multiple primaries and those who underwent pneumonectomy or have an unspecified surgical procedure were excluded. Differences in demographics and clinicopathological data were compared using Chi (χ2) test or Mann Whitney U test. Overall and cancer specific survival (OS, CSS) were estimated using Kaplan-Meier method and differences were compared using log-rank test. Cox-regression multivariable analysis (MVA) was performed to explore factors associated with worse CSS. Propensity-score matching analysis was done to compare survival differences between WR and Lob/Seg. RESULTS: A total of 22,350 patients with BC were identified, of them 4,450 met our inclusion criteria (3,511 Lob/Seg, vs. 939 WR). The median age was 59.0 years [interquartile range (IQR) =49.0-68.0], 67.6% were females and the median tumor size was 2 cm (1.5-3 cm). 4,119 patients had typical carcinoid (TC) and 331 had atypical carcinoid (AC). WR was performed more frequently in elderly patients, females, lower lobe tumors, TC's and in earlier stage disease. For patients with TC, there was no difference in CSS between WR and Lob/Seg in both the entire cohort (P=0.654) and in the propensity matched groups (P=0.900). However, for patients with AC, Lob/Seg was associated with better CSS compared to WR both in the entire cohort (P<0.001) and in the propensity matched groups (P=0.001). On MVA of the entire cohort, elderly patients, males, blacks, AC and advanced stages had worse CSS. While, the type of the procedure (WR vs. Lob/Seg) was not associated with CSS (HR =1.16, 95% CI: 0.85-1.60). CONCLUSIONS: A WR may offer equivalent CSS in well-selected patients with early-stage TC. An anatomic resection appears warranted in AC.

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