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1.
Lancet Oncol ; 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39369731

RESUMO

BACKGROUND: Use of fine-needle aspiration biopsy (FNAB) specimens on Xpert Breast Cancer STRAT4 Assay (STRAT4; Cepheid, Sunnyvale, CA, USA), a CE-marked in-vitro diagnostic medical device, could potentially increase access to breast cancer biomarker testing in resource-constrained settings. We aimed to assess the performance of a research use-only version of STRAT4 using FNAB specimens in Tanzania. METHODS: In this prospective diagnostic accuracy study, patients aged 18 years or older with palpable breast masses presenting to the FNAB Clinic at Muhimbili National Hospital (Dar es Salaam, Tanzania) were recruited consecutively. Patients who were pregnant, lactating, or had a previous diagnosis of breast cancer were excluded. STRAT4 testing was performed on off-label FNAB samples using four protocols: the 1 × protocol (using the standard lysate method) on FNAB smears (1 × FNAB), quick lysis and Maui protocols (both on FNAB smears), and the 1 × protocol on formalin-fixed paraffin-embedded (FFPE) cell block material (1 × cell block). For 1 × FNAB and 1 × cell block, tissue was processed using FFPE lysis reagent, incubated at 80°C with proteinase K, and followed by addition of 95% or higher ethanol. Quick lysis was processed using FFPE lysis reagent and 95% or higher ethanol, whereas Maui was processed using a proprietary research-use only lysis reagent. The primary outcomes were overall concordance, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of STRAT4 as compared with immunohistochemistry or immunohistochemistry plus fluorescence in-situ hybridisation performed on cell blocks using clinically validated protocols in a Clinical Laboratory Improvement Amendments-accredited laboratory at the University of California, San Francisco (San Francisco, CA, USA). FINDINGS: Between Nov 29, 2017, and Dec 17, 2020, 208 patients were enrolled. Of 208 cases, 51 (25%) were excluded from analysis because of insufficient tissue in the cell block or absent cell blocks, leaving 157 participants (all female) for analysis. For oestrogen receptor, 1 × FNAB had the best performance, with an overall concordance of 95% (95% CI 90-100), sensitivity of 94% (85-100), specificity of 97% (90-100), and AUC of 0·96 (0·81-1·00). For progesterone receptor, 1 × cell block had the best overall performance (overall concordance 89% [95% CI 84-95], sensitivity 91% [82-99], and specificity 89% [81-97], with an AUC of 0·93 [0·89-0·99]) and 1 × FNAB performed the best among the smear protocols, with a concordance of 84% (95% CI 74-93), sensitivity of 63% (43-82), specificity of 97% (92-100), and AUC of 0·91 (0·72-0·97). For HER2, Maui had the highest agreement, with an overall concordance of 93% (95% CI 89-98), sensitivity of 96% (88-100), specificity of 92% (87-98), and AUC of 0·95 (0·98-1·00). For Ki67, Maui had the best performance of smear protocols, with a concordance of 73% (95% CI 64-82), sensitivity of 70% (58-81), specificity of 81% (66-96), and AUC of 0·80 (0·54-0·82). INTERPRETATION: Processing FNAB samples with STRAT4 is feasible in Tanzania, and performance for the oestrogen receptor is robust. Further optimisation of STRAT4 for FNAB has the potential to improve timely access to breast cancer diagnostics in resource-constrained settings. FUNDING: US National Institutes of Health; UCSF Global Cancer Program, Helen Diller Family Comprehensive Cancer Center; UCSF Department of Pathology; and Cepheid.

2.
Bladder Cancer ; 10(1): 25-33, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38993527

RESUMO

BACKGROUND AND OBJECTIVE: Assessment of patients with hematuria (aH) remains a challenge in urological practice, balancing the benefits of diagnosing a potentially underlying bladder cancer (UCa) against the risks of possibly unnecessary diagnostic interventions. This study analyzes the potential of an mRNA-based urine assay, the Xpert® Bladder Cancer Detection- CE-IVD (Xpert BC-D), in patients with hematuria. MATERIALS AND METHODS: Overall, 368 patients with newly observed painless hematuria and no history of UCa were included in this observational study. Patients received urological workup, including urethrocystoscopy (WLC), upper tract imaging, urine cytology and Xpert BC-D. Patients with positive WLC were recommended to undergo tumor resection (TUR-B). RESULTS: After excluding non-assessable cases, 324 patients were considered for analysis (188 males, 136 females; median age: 61 years). Eight of twenty-eight patients with a positive TUR-B had Ta low grade (LG) tumors; the others were diagnosed with high grade (HG) lesions (Ta: 4, CIS: 2, T1:11, > T1:3). The Xpert BC-D was more sensitive than urine cytology (96% vs. 61%) (p = 0.002). Increased risk ratios (RR) were observed for gross hematuria, gender, urine cytology, and positive Xpert BC-D (all p < 0.05). Age and positive Xpert BC-D remained independent predictors of UCa in multivariate analysis. Simulating a triage with WLC restricted to patients with positive Xpert BC-D could have saved 240 (74.1%) assessments at the cost of missing one pTa LG tumor. CONCLUSIONS: The results suggest a potential role for Xpert BC-D in preselecting patients with hematuria for either further invasive diagnosis or an alternate diagnostic procedure.

3.
BJU Int ; 134(5): 755-762, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38717014

RESUMO

OBJECTIVE: To investigate and compare the performance of urinary cytology and the Xpert BC Monitor test in the detection of bladder cancer in various clinically significant patient cohorts, including patients with carcinoma in situ (CIS), in a prospective multicentre setting, aiming to identify potential applications in clinical practice. PATIENTS AND METHODS: A total of 756 patients scheduled for transurethral resection of bladder tumour (TURBT) were prospectively screened between July 2018 and December 2020 at six German University Centres. Central urinary cytology and Xpert BC Monitor tests were performed prior to TURBT. The diagnostic performance of urinary cytology and the Xpert BC Monitor was evaluated according to sensitivity (SN), specificity (SC), negative predictive value (NPV) and positive predictive value (PPV). Statistical comparison of urinary cytology and the Xpert BC Monitor was conducted using the McNemar test. RESULTS: Of 756 screened patients, 733 (568 male [78%]; median [interquartile range] age 72 [62-79] years) were included. Bladder cancer was present in 482 patients (65.8%) with 258 (53.5%) high-grade tumours. Overall SN, SC, NPV and PPV were 39%, 93%, 44% and 92% for urinary cytology, and 75%, 69%, 59% and 82% for the Xpert BC Monitor. In patients with CIS (concomitant or solitary), SN, SC, NPV and PPV were 59%, 93%, 87% and 50% for urinary cytology, and 90%, 69%, 95% and 50% for the Xpert BC Monitor. The Xpert BC Monitor missed four tumours (NPV = 98%) in patients with solitary CIS, while potentially avoiding 63.3% of TURBTs in inconclusive or negative cystoscopy and a negative Xpert result. CONCLUSION: Positive urinary cytology may indicate bladder cancer and should be taken seriously. The Xpert BC Monitor may represent a useful diagnostic tool for correctly identifying patients with solitary CIS and unsuspicious or inconclusive cystoscopy.


Assuntos
Carcinoma in Situ , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/urina , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Carcinoma in Situ/urina , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/patologia , Estudos Prospectivos , Sensibilidade e Especificidade , Citodiagnóstico/métodos , Valor Preditivo dos Testes
4.
Breast Cancer Res ; 26(1): 24, 2024 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-38321542

RESUMO

BACKGROUND: Overexpression of human epidermal growth factor receptor 2 (HER2) caused by HER2 gene amplification is a driver in breast cancer tumorigenesis. We aimed to investigate the prognostic significance of manual scoring and digital image analysis (DIA) algorithm assessment of HER2 copy numbers and HER2/CEP17 ratios, along with ERBB2 mRNA levels among early-stage HER2-positive breast cancer patients treated with trastuzumab. METHODS: This retrospective study comprised 371 early HER2-positive breast cancer patients treated with adjuvant trastuzumab, with HER2 re-testing performed on whole tumor sections. Digitized tumor tissue slides were manually scored and assessed with uPath HER2 Dual ISH image analysis, breast algorithm. Targeted ERBB2 mRNA levels were assessed by the Xpert® Breast Cancer STRAT4 Assay. HER2 copy number and HER2/CEP17 ratio from in situ hybridization assessment, along with ERBB2 mRNA levels, were explored in relation to recurrence-free survival (RFS). RESULTS: The analysis showed that patients with tumors with the highest and lowest manually counted HER2 copy number levels had worse RFS than those with intermediate levels (HR = 2.7, CI 1.4-5.3, p = 0.003 and HR = 2.1, CI 1.1-3.9, p = 0.03, respectively). A similar trend was observed for HER2/CEP17 ratio, and the DIA algorithm confirmed the results. Moreover, patients with tumors with the highest and the lowest values of ERBB2 mRNA had a significantly worse prognosis (HR = 2.7, CI 1.4-5.1, p = 0.003 and HR = 2.8, CI 1.4-5.5, p = 0.004, respectively) compared to those with intermediate levels. CONCLUSIONS: Our findings suggest that the association between any of the three HER2 biomarkers and RFS was nonlinear. Patients with tumors with the highest levels of HER2 gene amplification or ERBB2 mRNA were associated with a worse prognosis than those with intermediate levels, which is of importance to investigate in future clinical trials studying HER2-targeted therapy.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Trastuzumab/uso terapêutico , Neoplasias da Mama/patologia , Prognóstico , Estudos Retrospectivos , Receptor ErbB-2/metabolismo , RNA Mensageiro
5.
Clin Case Rep ; 11(9): e7943, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37744626

RESUMO

Despite emphasis for emergent surgical treatment of Stanford type A aortic dissections, pregnant patients that are clinically stable may safely receive a staged approach instead, with delivery followed by delayed dissection repair.

6.
J Cardiothorac Surg ; 18(1): 255, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37658440

RESUMO

Current myocardial infarction treatments focus on improving hemodynamics rather than addressing the problem of lost myocardium impairing left ventricular function. Epicardial infarct repair with a bioactive patch placed on the ischemic area is an emerging approach to promote endogenous myocardial repair. We report the use of a second-generation CorMatrix-extracellular matrix (ECM) patch as an adjunct to surgical revascularization in treating a young patient with diffuse, multivessel coronary artery disease unamenable to PCI and a large anterior myocardial infarction. The progressive myocardial scar shrinkage and increase in left ventricular ejection fraction from 10 to 51% are generally not observed with surgical revascularization therapy alone, suggesting this new patch has adjunctive potential to current revascularization therapy.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Volume Sistólico , Função Ventricular Esquerda , Infarto do Miocárdio/cirurgia , Matriz Extracelular
7.
Sci Rep ; 13(1): 15437, 2023 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-37723173

RESUMO

To determine whether Xpert bladder cancer monitor, a noninvasive PCR-based biomarker test, can predict the need for 2nd transurethral resection of the bladder (TURB) better than clinical assessment. Patients scheduled for TURB were prospectively screened. After initial TURB, patients were assigned to 2nd TURB or follow-up cystoscopy at 3 months (FU) by clinicians' discretion. Central urine cytology and Xpert monitor tests were performed prior to the 1st TURB and 2nd TURB or FU, respectively. Statistical analysis to compare clinical assessment and Xpert monitor comprised sensitivity (SENS), specificity (SPEC), NPV and PPV. Of 756 screened patients, 171 were included (114 with 2nd TURB, 57 with FU). Residual tumors were detected in 34 patients who underwent 2nd TURB, and recurrent tumors were detected in 2 patients with FU. SENS and SPEC of Xpert monitor were 83.3% and 53.0%, respectively, PPV was 32.6% and NPV was 92.1%. Clinical risk assessment outperformed Xpert monitor. In patients with pTa disease at initial TURB, Xpert monitor revealed a NPV of 96%. Xpert monitor was not superior than clinical assessment in predicting the need for 2nd TURB. It might be an option to omit 2nd TURB for selected patients with pTa disease.


Assuntos
Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/diagnóstico , Bexiga Urinária , Cistoscopia , Neoplasia Residual , Reação em Cadeia da Polimerase
8.
J Cardiothorac Surg ; 18(1): 221, 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37420308

RESUMO

Infective endocarditis caused by Mycobacterium abscessus is an uncommon event that, when it does occur, usually requires surgical valve replacement. The pulmonary valve is the least common heart valve involved in infective endocarditis. We present a rare case of isolated pulmonary valve endocarditis with Mycobacterium abscessus in a patient with recurrent sternal infections following repeated coronary artery bypass.


Assuntos
Endocardite Bacteriana , Endocardite , Mycobacterium abscessus , Valva Pulmonar , Humanos , Valva Pulmonar/cirurgia , Valva Pulmonar/microbiologia , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/cirurgia , Endocardite Bacteriana/microbiologia , Ponte de Artéria Coronária
9.
ACS Chem Biol ; 18(8): 1880-1890, 2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-37494676

RESUMO

Ghrelin O-acyltransferase (GOAT) plays a central role in the maturation and activation of the peptide hormone ghrelin, which performs a wide range of endocrinological signaling roles. Using a tight-binding fluorescent ghrelin-derived peptide designed for high selectivity for GOAT over the ghrelin receptor GHSR, we demonstrate that GOAT interacts with extracellular ghrelin and facilitates ligand cell internalization in both transfected cells and prostate cancer cells endogenously expressing GOAT. Coupled with enzyme mutagenesis, ligand uptake studies support the interaction of the putative histidine general base within GOAT with the ghrelin peptide acylation site. Our work provides a new understanding of GOAT's catalytic mechanism, establishes that GOAT can interact with ghrelin and other peptides located outside the cell, and raises the possibility that other peptide hormones may exhibit similar complexity in their intercellular and organismal-level signaling pathways.


Assuntos
Grelina , Via Secretória , Animais , Masculino , Aciltransferases/metabolismo , Corantes , Grelina/metabolismo , Ligantes
10.
Mod Pathol ; 36(5): 100128, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36889057

RESUMO

The assessment of the expression of programmed cell death ligand-1 (PD-L1) using immunohistochemistry (IHC) has been controversial since its introduction. The methods of assessment and the range of assays and platforms contribute to confusion. Perhaps the most challenging aspect of PD-L1 IHC is the combined positive score (CPS) method of interpretation of IHC results. Although the CPS method is prescribed for more indications than any other PD-L1 scoring system, its reproducibility has never been rigorously assessed. In this study, we collected a series of 108 gastric or gastroesophageal junction cancer cases, stained them using the Food and Drug Administration-approved 22C3 assay, scanned them, and then circulated them to 14 pathologists at 13 institutions for the assessment of interpretative concordance for the CPS system. We found that higher cut points (10 or 20) performed better than a CPS of <1 or >1. We used the Observers Needed to Evaluate Subjective Tests algorithm to assess how the CPS system might perform in the real-world setting and found that the cut points of <1 or >1 showed an overall percent agreement of only 30% among the pathologist raters, with a plateau occurring at 8 raters. The raters performed better at higher cut points. However, the best cut point of <20 versus that of >20 was still disappointing, with a plateau at an overall percent agreement of 70% (at 7 raters). Although there is no ground truth for CPS, we compared the score with quantitative messenger RNA measurement and showed no relationship between the score (at any cut point) and messenger RNA amount. In summary, we showed that CPS shows high subjective variability among pathologist readers and is likely to perform poorly in the real-world setting. This system may be the root cause of the poor specificity and relatively low predictive value of IHC companion diagnostic tests for PD-1 axis therapies that use the CPS system.


Assuntos
Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Apoptose , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Junção Esofagogástrica/patologia , Imuno-Histoquímica , Ligantes , Patologistas , Reprodutibilidade dos Testes , Neoplasias Gástricas/diagnóstico
11.
Clin Cancer Res ; 29(4): 784-790, 2023 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-36534524

RESUMO

PURPOSE: We previously demonstrated that high levels of circulating methylated DNA are associated with subsequent disease progression in women with metastatic breast cancer (MBC). In this study, we evaluated the clinical utility of a novel liquid biopsy-breast cancer methylation (LBx-BCM) prototype assay using the GeneXpert cartridge system for early assessment of disease progression in MBC. EXPERIMENTAL DESIGN: The 9-marker LBx-BCM prototype assay was evaluated in TBCRC 005, a prospective biomarker study, using plasma collected at baseline, week 4, and week 8 from 144 patients with MBC. RESULTS: At week 4, patients with MBC with high cumulative methylation (CM) had a significantly shorter median PFS (2.88 months vs. 6.60 months, P = 0.001) and OS (14.52 months vs. 22.44 months, P = 0.005) compared with those with low CM. In a multivariable model, high versus low CM was also associated with shorter PFS (HR, 1.90; 95% CI, 1.20-3.01; P = 0.006). Change in CM from baseline to week 4 (OR, 4.60; 95% CI, 1.77-11.93; P = 0.002) and high levels of CM at week 4 (OR, 2.78; 95% CI, 1.29-5.99; P = 0.009) were associated with progressive disease at the time of first restaging. A robust risk model based on week 4 circulating CM levels was developed to predict disease progression as early as 3 months after initiating a new treatment. CONCLUSIONS: The automated LBx-BCM prototype assay is a promising clinical tool for detecting disease progression a month after initiating treatment in women with MBC undergoing routine care. The next step is to validate its clinical utility for specific treatments.


Assuntos
Neoplasias da Mama , Ácidos Nucleicos Livres , Feminino , Humanos , Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/tratamento farmacológico , Progressão da Doença , Biópsia Líquida , Metilação
12.
Am Surg ; 89(5): 1829-1832, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35315285

RESUMO

OBJECTIVES: Minimally invasive esophagectomy is a technically challenging procedure that been associated with better outcomes at high-volume tertiary care centers. Louisiana is one of the most impoverished states, and travel to a "destination center" is not an option for many patients. We hypothesize that patients can obtain excellent surgical outcomes following MIE in a comprehensive community cancer center. METHODS: We identified all patients who underwent totally robotic MIE by a single surgeon at our center from July 2018 to November 2020. All cases were performed using totally robotic Ivor Lewis technique with intrathoracic isoperistaltic esophagogastrostomy. Incidence, demographics, treatment, and outcomes were compared before and after first 10 cases using Student's t-test. RESULTS: We identified 21 patients: 16 male and 5 female. Mean age 65 (49-85). 19 patients underwent MIE for malignancy; 18 of these received neoadjuvant therapy. OR time decreased following the first 10 cases (502 vs. 408 minutes, P = 0.0127). Average lymph node harvest was 14 (4-23 nodes). Positive margin rate was 0%. Mean length of stay trended towards a decrease after the first 10 cases (11 vs. 9 days, P = NS). There were no leaks or strictures. Thirty-day readmission was five patients. Ninety-day mortality was 0%. CONCLUSION: These outcomes rival those of high-volume referral centers and demonstrate that totally robotic MIE can be performed with excellent outcomes in community center. These data call into question the need for all patients to travel to "destination centers" to receive complex oncologic surgery.


Assuntos
Neoplasias Esofágicas , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Masculino , Feminino , Idoso , Esofagectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Neoplasias Esofágicas/patologia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Resultado do Tratamento , Laparoscopia/métodos
14.
Cancer Res Commun ; 2(6): 391-401, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-36046124

RESUMO

Current molecular liquid biopsy assays to detect recurrence or monitor response to treatment require sophisticated technology, highly trained personnel, and a turnaround time of weeks. We describe the development and technical validation of an automated Liquid Biopsy for Breast Cancer Methylation (LBx-BCM) prototype, a DNA methylation detection cartridge assay that is simple to perform and quantitatively detects nine methylated markers within 4.5 h. LBx-BCM demonstrated high interassay reproducibility when analyzing exogenous methylated DNA (75-300 DNA copies) spiked into plasma (Coefficient of Variation, CV = 7.1 - 10.9%) and serum (CV = 19.1 - 36.1%). It also demonstrated high interuser reproducibility (Spearman r = 0.887, P < 0.0001) when samples of metastatic breast cancer (MBC, N = 11) and normal control (N = 4) were evaluated independently by two users. Analyses of interplatform reproducibility indicated very high concordance between LBx-BCM and the reference assay, cMethDNA, among 66 paired plasma samples (MBC N = 40, controls N = 26; Spearman r = 0.891; 95% CI = 0.825 - 0.933, P< 0.0001). LBx-BCM achieved a ROC AUC = 0.909 (95% CI = 0.836 - 0.982), 83% sensitivity and 92% specificity; cMethDNA achieved a ROC AUC = 0.896 (95% CI = 0.817 - 0.974), 83% sensitivity and 92% specificity in test set samples. The automated LBx-BCM cartridge prototype is fast, with performance levels equivalent to the highly sensitive, manual cMethDNA method. Future prospective clinical studies will evaluate LBx-BCM detection sensitivity and its ability to monitor therapeutic response during treatment for advanced breast cancer.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Reprodutibilidade dos Testes , Metilação de DNA/genética , DNA , Biópsia Líquida
16.
J Thorac Oncol ; 17(9): 1078-1085, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35764237

RESUMO

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have become standard of care in lung cancer management, but only a relatively small percentage of patients treated respond. Current predictive biomarkers, including immunohistochemical detection of programmed death-ligand 1 (PD-L1), are insufficient for determining who will respond or, more importantly in the adjuvant setting, who will not respond to ICI therapy. Here, we investigate an alternative method of assessment of PD-L1 to predict nonresponse. METHODS: This study uses a research use only quantitative real-time reverse transcription polymerase chain reaction assay on the GeneXpert system, to test for the association between four target immune genes, CD274 (PD-L1), PDCD1LG2 (programmed death-ligand 2 [PD-L2]), CD8A, and IRF1, and response to ICI therapy. Tissues were collected from 122 patients with advanced NSCLC before ICI therapy in a retrospective cohort, macrodissected, and analyzed using the GeneXpert. RESULTS: Both high PD-L1 and PD-L2 mRNA expression levels were associated with improved long-term benefit at 24 months (p = 0.047 for both PD-L1 and PD-L2) and overall survival (PD-L1, p = 0.048; PD-L2, p = 0.049). Both PD-L1 and PD-L2 mRNA levels were higher in patients with KRAS mutations. Most importantly, low PD-L1 mRNA level had a high negative predictive value of 0.92 for absence of long-term benefit. CONCLUSIONS: With further validation of this assay in low-stage patients, an assessment of PD-L1 mRNA rather than protein, could be a method to determine which low-stage patients that should not be treated with ICIs in the adjuvant setting. This approach may also be a useful objective method for selecting patients for treatment in the advanced setting.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antígeno B7-H1 , Humanos , Imunoterapia , Ligantes , Valor Preditivo dos Testes , RNA Mensageiro , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos
17.
Mol Biol Cell ; 33(9): br14, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35609215

RESUMO

Polo-like-kinase (PLK) 1 activity is associated with maintaining the functional and physical properties of the centrosome's pericentriolar matrix (PCM). In this study, we use a multimodal approach of human cells (HeLa), zebrafish embryos, and phylogenic analysis to test the role of a PLK1 binding protein, cenexin, in regulating the PCM. Our studies identify that cenexin is required for tempering microtubule nucleation by maintaining PCM cohesion in a PLK1-dependent manner. PCM architecture in cenexin-depleted zebrafish embryos was rescued with wild-type human cenexin, but not with a C-terminal cenexin mutant (S796A) deficient in PLK1 binding. We propose a model where cenexin's C terminus acts in a conserved manner in eukaryotes, excluding nematodes and arthropods, to sequester PLK1 that limits PCM substrate phosphorylation events required for PCM cohesion.


Assuntos
Proteínas de Ciclo Celular , Centrossomo , Proteínas de Choque Térmico , Proteínas Serina-Treonina Quinases , Proteínas Proto-Oncogênicas , Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Humanos , Proteínas de Ciclo Celular/metabolismo , Centrossomo/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Células HeLa , Microtúbulos/metabolismo , Fosforilação , Ligação Proteica , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/deficiência , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Quinase 1 Polo-Like
18.
Front Oncol ; 12: 832835, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35155263

RESUMO

OBJECTIVES: To test the hypothesis that patients under active surveillance (AS) for Non-muscle Invasive Bladder Cancer (NMIBC) who were negative on longitudinal re-testing by the Xpert® Bladder Cancer Monitor (Xpert BC Monitor) assay may avoid unnecessary cystoscopies and urine cytology (UC). SUBJECTS/PATIENTS OR MATERIALS AND METHODS: This is a prospective cohort study of patients enrolled in the AS protocol for recurrent NMIBC (Bladder Cancer Italian Active Surveillance, BIAS project), whose urine samples were analyzed by Xpert BC Monitor upon entry in the study (T0). Patients who had a negative Xpert test and did not fail AS, underwent additional Xpert tests after 4 (T1), 8 (T2), and 12 (T3) months. The clinical utility of Xpert was assessed by determining the number of cystoscopies and UC that could be avoided within 1 year. RESULTS: Overall, 139 patients were tested with Xpert at T0. Median follow-up was 23 (IQR 17-27) months. Sixty-eight (48.9%) patients failed AS, 65 (46.7%) are currently on AS, and 6 (4.3%) were lost at follow-up. At T0 57 (41.0%) patients had a negative test and 36 (63.2%) are still in AS. In patients with 2 consecutives negative Xpert tests, we could have avoided 73.9% of unnecessary cystoscopies, missing 26.4% failure, up to avoid all cystoscopies with 4 negative tests missing only 12% of failure. All the patients with negative Xpert had negative UC. Failure-free-survival at median follow-up (23 month) stratified for having 0, 1, or ≥2 negative tests was 67.0, 55.1. and 84.1, respectively. CONCLUSION: Our findings suggest that Xpert BC Monitor assay, when it is longitudinally repeated, could significantly reduce the number of unnecessary cystoscopies and UC during their follow-up.

20.
J Card Surg ; 36(11): 4238-4242, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34499373

RESUMO

BACKGROUND: To determine if racial disparities exist between African Americans (AA) and Non-Hispanic Whites (NHW) for patients undergoing repair of acute type A aortic dissection (ATAAD) at a rural tertiary academic medical center. METHODS: There were 215 consecutive AA and NHW patients who underwent ATAAD repair at our institution from 1999 to 2019 included in a retrospective analysis of our Society of Thoracic Surgeons Adult Cardiac Surgery Database. Statistical analysis was performed with a p value of less than .05 considered statistically significant. RESULTS: Patients undergoing ATAAD repair were 47% AA despite comprising only 27% of the total population in our region. AAs were significantly younger (54.0 vs. 61.2 years), were more likely to be hypertensive (94.1% vs. 79.7%), had higher creatinine levels (1.7 vs. 1.1 mg/dL), and higher body mass index (30.8 vs. 28.1 kg/m2 ) (all p values < .006). There were no significant differences in type of repair or intraoperative variables. A logistic regression analysis showed AAs had an increased rate of postoperative acute renal failure not requiring hemodialysis when compared to NHWs (20.8% vs. 10.6%, p value = .042). Thirty-day mortality was not significantly different (15.7% vs. 13.4%) nor was 1-year survival (78% vs. 79%) in AAs and NHWs, respectively. CONCLUSIONS: Despite AAs having more medical comorbidities at presentation, there were no differences in short- and intermediate-term survival. In our catchment of 1.8 million people, AAs appear to undergo ATAAD repair at a disproportionate rate versus NHWs. These findings may alter strategies for surveillance and prevention of aortic disease in this high-risk population.


Assuntos
Dissecção Aórtica , Centros Médicos Acadêmicos , Adulto , Dissecção Aórtica/cirurgia , Humanos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
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