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1.
Heart Lung Circ ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38981830

RESUMO

BACKGROUND: Heart failure (HF) is associated with high mortality, but there are limited reports on the underlying cause of death. This study reports short-, medium- and long-term cause-specific mortality following first-ever HF hospitalisation in New Zealand. METHOD: First-ever HF hospitalisations were identified from hospital discharge coding between 2010 and 2013. Mortality outcomes were obtained via anonymised linkage to national datasets. Short (0-30 days), medium (31-364 days), and long-term (1-5 years) mortality rates were identified. Cause of death was identified from death certification coding and classified as cardiovascular and non-cardiovascular. Cox regression analysis was performed to adjust for confounding variables. RESULTS: A cohort of 34,264 individuals with first-ever HF hospitalisation were identified. Mean age was 75.8±13 years and 50.5% were male. A total of 21,637 (63.1%) died within 5 years of hospitalisation; 4,122 (12.0%) within the first 30 days, 6,358 (18.6%) between 31-364 days, and 11,157 (32.6%) between 1 and 5 years. Older age, male gender, Maori ethnicity, higher socioeconomic deprivation and increased comorbidity were independent factors associated with higher all-cause mortality. Cardiovascular causes accounted for 51% of total deaths. Cardiovascular mortality was 6.0%, 9.5%, and 16.7% at 30 days, 31-364 days, and 1-5 years, respectively. The most common causes of non-cardiovascular mortality were neoplasms, chronic respiratory diseases and infections, accounting for 14.6%, 11.0%, and 5.5% of total deaths respectively. Comorbidity was associated with higher non-cardiovascular mortality (hazard ratio [HR] 3.35; 95% confidence interval [CI] 3.16-3.55) but not cardiovascular mortality (HR 0.79; 95% CI 0.72-0.86). CONCLUSIONS: In New Zealand, mortality following first-ever HF hospitalisation is high. Non-cardiovascular death is common and there are ethnic inequities.

3.
Cell Rep Med ; 5(5): 101547, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38703764

RESUMO

Non-clear cell renal cell carcinomas (non-ccRCCs) encompass diverse malignant and benign tumors. Refinement of differential diagnosis biomarkers, markers for early prognosis of aggressive disease, and therapeutic targets to complement immunotherapy are current clinical needs. Multi-omics analyses of 48 non-ccRCCs compared with 103 ccRCCs reveal proteogenomic, phosphorylation, glycosylation, and metabolic aberrations in RCC subtypes. RCCs with high genome instability display overexpression of IGF2BP3 and PYCR1. Integration of single-cell and bulk transcriptome data predicts diverse cell-of-origin and clarifies RCC subtype-specific proteogenomic signatures. Expression of biomarkers MAPRE3, ADGRF5, and GPNMB differentiates renal oncocytoma from chromophobe RCC, and PIGR and SOSTDC1 distinguish papillary RCC from MTSCC. This study expands our knowledge of proteogenomic signatures, biomarkers, and potential therapeutic targets in non-ccRCC.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Renais , Neoplasias Renais , Proteogenômica , Humanos , Proteogenômica/métodos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/metabolismo , Transcriptoma/genética , Masculino , Feminino , Pessoa de Meia-Idade , Regulação Neoplásica da Expressão Gênica
4.
JAMA Oncol ; 10(6): 726-736, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38635241

RESUMO

Importance: Benefits of prostate cancer (PCa) screening with prostate-specific antigen (PSA) alone are largely offset by excess negative biopsies and overdetection of indolent cancers resulting from the poor specificity of PSA for high-grade PCa (ie, grade group [GG] 2 or greater). Objective: To develop a multiplex urinary panel for high-grade PCa and validate its external performance relative to current guideline-endorsed biomarkers. Design, Setting, and Participants: RNA sequencing analysis of 58 724 genes identified 54 markers of PCa, including 17 markers uniquely overexpressed by high-grade cancers. Gene expression and clinical factors were modeled in a new urinary test for high-grade PCa (MyProstateScore 2.0 [MPS2]). Optimal models were developed in parallel without prostate volume (MPS2) and with prostate volume (MPS2+). The locked models underwent blinded external validation in a prospective National Cancer Institute trial cohort. Data were collected from January 2008 to December 2020, and data were analyzed from November 2022 to November 2023. Exposure: Protocolized blood and urine collection and transrectal ultrasound-guided systematic prostate biopsy. Main Outcomes and Measures: Multiple biomarker tests were assessed in the validation cohort, including serum PSA alone, the Prostate Cancer Prevention Trial risk calculator, and the Prostate Health Index (PHI) as well as derived multiplex 2-gene and 3-gene models, the original 2-gene MPS test, and the 18-gene MPS2 models. Under a testing approach with 95% sensitivity for PCa of GG 2 or greater, measures of diagnostic accuracy and clinical consequences of testing were calculated. Cancers of GG 3 or greater were assessed secondarily. Results: Of 761 men included in the development cohort, the median (IQR) age was 63 (58-68) years, and the median (IQR) PSA level was 5.6 (4.6-7.2) ng/mL; of 743 men included in the validation cohort, the median (IQR) age was 62 (57-68) years, and the median (IQR) PSA level was 5.6 (4.1-8.0) ng/mL. In the validation cohort, 151 (20.3%) had high-grade PCa on biopsy. Area under the receiver operating characteristic curve values were 0.60 using PSA alone, 0.66 using the risk calculator, 0.77 using PHI, 0.76 using the derived multiplex 2-gene model, 0.72 using the derived multiplex 3-gene model, and 0.74 using the original MPS model compared with 0.81 using the MPS2 model and 0.82 using the MPS2+ model. At 95% sensitivity, the MPS2 model would have reduced unnecessary biopsies performed in the initial biopsy population (range for other tests, 15% to 30%; range for MPS2, 35% to 42%) and repeat biopsy population (range for other tests, 9% to 21%; range for MPS2, 46% to 51%). Across pertinent subgroups, the MPS2 models had negative predictive values of 95% to 99% for cancers of GG 2 or greater and of 99% for cancers of GG 3 or greater. Conclusions and Relevance: In this study, a new 18-gene PCa test had higher diagnostic accuracy for high-grade PCa relative to existing biomarker tests. Clinically, use of this test would have meaningfully reduced unnecessary biopsies performed while maintaining highly sensitive detection of high-grade cancers. These data support use of this new PCa biomarker test in patients with elevated PSA levels to reduce the potential harms of PCa screening while preserving its long-term benefits.


Assuntos
Biomarcadores Tumorais , Gradação de Tumores , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/genética , Neoplasias da Próstata/urina , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Idoso , Biomarcadores Tumorais/urina , Biomarcadores Tumorais/genética , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Detecção Precoce de Câncer/métodos
5.
Bioorg Chem ; 144: 107176, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38330721

RESUMO

Repurposing drugs can significantly reduce the time and costs associated with drug discovery and development. However, many drug compounds possess intrinsic fluorescence, resulting in aberrations such as auto-fluorescence, scattering and quenching, in fluorescent high-throughput screening assays. To overcome these drawbacks, time-resolved technologies have received increasing attention. In this study, we have developed a rapid and efficient screening platform based on time-resolved emission spectroscopy in order to screen for inhibitors of the DNA repair enzyme, uracil-DNA glycosylase (UDG). From a database of 1456 FDA/EMA-approved drugs, sodium stibogluconate was discovered as a potent UDG inhibitor. This compound showed synergistic cytotoxicity against 5-fluorouracil-resistant cancer cells. This work provides a promising future for time-resolved technologies for high-throughput screening (HTS), allowing for the swift identification of bioactive compounds from previously overlooked scaffolds due to their inherent fluorescence properties.


Assuntos
Neoplasias da Próstata , Uracila-DNA Glicosidase , Humanos , Masculino , Uracila-DNA Glicosidase/química , Oligonucleotídeos , Gluconato de Antimônio e Sódio , Avaliação Pré-Clínica de Medicamentos , Reposicionamento de Medicamentos , Detecção Precoce de Câncer
7.
Int J Biol Macromol ; 259(Pt 1): 129211, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38184034

RESUMO

The overexpression and overactivation of epidermal growth factor receptor (EGFR) are frequently observed in human cancers, including squamous cell carcinoma and adenocarcinoma. In this study, a covalent EGFR probe was developed by conjugating afatinib to an iridium(III) scaffold. Complex 1 showed enhanced luminescence in living epidermoid squamous carcinoma A431 cells compared to other cell lines, via engaging EGFR as confirmed via CETSA and knockdown experiments. Moreover, complex 1 inhibited downstream targets of EGFR in cellulo with repression persisting after removal of the complex, indicating an irreversible mode of inhibition. Finally, complex 1 showed potent antiproliferative activity against A431 cells with comparable potency to afatinib alone. To our knowledge, complex 1 is the first EGFR covalent inhibitor based on an iridium scaffold reported in the literature, with the potential to be further explored as a theranostic agent in the future.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Afatinib , Irídio/farmacologia , Quinazolinas/farmacologia , Receptores ErbB/metabolismo , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases/farmacologia
8.
J Artif Organs ; 27(1): 57-64, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36752993

RESUMO

The AtriClip device enables the safe and reproducible epicardial clipping of the left atrial appendage. Transapical off-pump beating heart mitral valve repair using NeoChord DS100 Artificial Chordae Delivery System has matured and become more standardized. We aim to evaluate the feasibility of combining NeoChord repair and left atrial appendage exclusion in a single procedure through the same minithoracotomy in patients with mitral valve prolapse and atrial fibrillation. From 2018 to 2019, seven patients with severe mitral regurgitation and atrial fibrillation underwent transesophageal echocardiography-guided transapical off-pump mitral valve repair with the novel NeoChord DS 1000 system and concomitant left atrial appendage exclusion using the AtriClip Pro II device. Both procedures were performed via left mini-thoracotomy. The AtriClip device was applied after the NeoChord repair was done. All seven patients had less than moderate mitral regurgitation after the NeoChord repair and successful left atrial appendage occlusion. There were no device or procedure-related complications. Clinical follow-up revealed significant symptomatic improvement, and no cardiovascular complications were reported. Transesophageal echocardiography at 6-12 months post-procedure showed stable left atrial appendage occlusion with no residual flow between the left atrium and the left atrial appendage and a stump of less than 5 mm. Beating heart epicardial clipping of the left atrial appendage using AtriClip concomitant with transapical mitral valve repair using Neochord DS 1000 system is a feasible and safe treatment option in mitral valve prolapse and atrial fibrillation in patients with limited indications. However, its safety needs to be confirmed in a larger series of patients.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Prolapso da Valva Mitral , Humanos , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/cirurgia , Prolapso da Valva Mitral/complicações , Prolapso da Valva Mitral/cirurgia , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Implante de Prótese de Valva Cardíaca/métodos , Fibrilação Atrial/complicações , Fibrilação Atrial/cirurgia , Estudos de Viabilidade , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/cirurgia , Resultado do Tratamento , Cordas Tendinosas
9.
Eur J Med Chem ; 264: 115995, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38043488

RESUMO

Hepatocellular carcinoma (HCC) is a major contributor to global mortality rates, but current treatment options have limitations. Advanced theranostics are needed to effectively integrate diagnosis and therapeutic of HCC. Glycyrrhetinic acid (GA) has abundant binding sites with glycyrrhetinic acid receptors (GA-Rs) on the surface of HCC cells and has also been reported to possess ligands with mitochondrial-targeting capability but with limited efficacy. Herein, we report a near-infrared (NIR) luminescent theranostic complex 1 through conjugating an iridium(III) complex to GA, which exhibits the desired photophysical properties and promotes mitochondrial-targeting capability. Complex 1 was selectively taken up by HepG2 liver cancer cells and was imaged within mitochondria with NIR emission. Complex 1 targeted mitochondria and opened mitochondrial permeability transition pores (MPTPs), resulting in ROS accumulation, mitochondrial damage, disruption of Bax/Bcl-2 equilibrium, and tumor cell apoptosis, resulting in significantly improved anticancer activity compared to GA. This work offers a methodology for developing multifunctional theranostic probes with amplified specificity and efficacy.


Assuntos
Carcinoma Hepatocelular , Ácido Glicirretínico , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Medicina de Precisão , Irídio/farmacologia , Irídio/química , Ácido Glicirretínico/farmacologia , Ácido Glicirretínico/química , Mitocôndrias/metabolismo , Linhagem Celular Tumoral
10.
Surg Obes Relat Dis ; 20(3): 245-252, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38057250

RESUMO

BACKGROUND: There is currently a lack of consensus regarding the timing of ventral hernia repair relative to bariatric surgery. OBJECTIVES: To compare outcomes between patients undergoing simultaneous and selectively deferred ventral hernia repair and bariatric surgery. SETTING: High volume UPPER gastrointestinal and Bariatric Unit. Sydney, Australia. METHODS: A retrospective case series from a single institution's prospectively collected database (2003-21) was performed to determine the characteristics and outcomes in patients having simultaneous and deferred hernia repair relative to their bariatric surgery. RESULTS: In our patient cohort (N = 134), 111 patients underwent simultaneous repair and 23 had a deferred procedure. Of the simultaneous patients, 95 (85.6%) underwent resection bariatric surgery. The median operative time in the simultaneous versus deferred groups was 155 versus 287 minutes and the length of stay was 3 versus 7 days. There has been one (.9%) mesh infection requiring explant, in an open, simultaneous repair undertaken in a gastric band patient, 3 (2.8%) infected seromas, 1 (.9%) surgical site infection, and 8 (7.5%) hernia recurrences in the simultaneous group. The deferred group has had no mesh infections, no hernia recurrence, and 2 (9.5%) infected seromas to date. There was 1 mortality in the simultaneous cohort (simultaneous gastric bypass group), from a massive Pulmonary Embolism (<30 days postoperatively) and one in the deferred group from an interval small bowel obstruction. CONCLUSIONS: Simultaneous ventral hernia repair with bariatric surgery had a low rate of infection and a low mesh explant rate, even when coupled with resection bariatric surgery in this series. A combined approach may be safe, even in the clean-contaminated surgical context.


Assuntos
Cirurgia Bariátrica , Hérnia Ventral , Humanos , Herniorrafia/métodos , Estudos Retrospectivos , Seroma/cirurgia , Hérnia Ventral/cirurgia , Cirurgia Bariátrica/efeitos adversos , Cirurgia Bariátrica/métodos , Telas Cirúrgicas , Resultado do Tratamento
11.
Mol Cell Proteomics ; 23(1): 100687, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38029961

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer types, partly because it is frequently identified at an advanced stage, when surgery is no longer feasible. Therefore, early detection using minimally invasive methods such as blood tests may improve outcomes. However, studies to discover molecular signatures for the early detection of PDAC using blood tests have only been marginally successful. In the current study, a quantitative glycoproteomic approach via data-independent acquisition mass spectrometry was utilized to detect glycoproteins in 29 patient-matched PDAC tissues and sera. A total of 892 N-linked glycopeptides originating from 141 glycoproteins had PDAC-associated changes beyond normal variation. We further evaluated the specificity of these serum-detectable glycoproteins by comparing their abundance in 53 independent PDAC patient sera and 65 cancer-free controls. The PDAC tissue-associated glycoproteins we have identified represent an inventory of serum-detectable PDAC-associated glycoproteins as candidate biomarkers that can be potentially used for the detection of PDAC using blood tests.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Biomarcadores Tumorais/metabolismo , Neoplasias Pancreáticas/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Glicoproteínas , Espectrometria de Massas
12.
Braz. oral res. (Online) ; 38: e021, 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS, BBO - Odontologia | ID: biblio-1550156

RESUMO

Abstract The present study aimed to evaluate the influence of titanium surface nanotopography on the initial bacterial adhesion process by in vivo and in vitro study models. Titanium disks were produced and characterized according to their surface topography: machined (Ti-M), microtopography (Ti-Micro), and nanotopography (Ti-Nano). For the in vivo study, 18 subjects wore oral acrylic splints containing 2 disks from each group for 24 h (n = 36). After this period, the disks were removed from the splints and evaluated by microbial culture method, scanning electron microscopy (SEM), and qPCR for quantification of Streptococcus oralis, Actinomyces naeslundii, Fusobacterium nucleatum, as well as total bacteria. For the in vitro study, adhesion tests were performed with the species S. oralis and A. naeslundii for 24 h. Data were compared by ANOVA, with Tukey's post-test. Regarding the in vivo study, both the total aerobic and total anaerobic bacteria counts were similar among groups (p > 0.05). In qPCR, there was no difference among groups of bacteria adhered to the disks (p > 0.05), except for A. naeslundii, which was found in lower proportions in the Ti-Nano group (p < 0.05). In the SEM analysis, the groups had a similar bacterial distribution, with a predominance of cocci and few bacilli. In the in vitro study, there was no difference in the adhesion profile for S. oralis and A. naeslundii after 24 h of biofilm formation (p > 0.05). Thus, we conclude that micro- and nanotopography do not affect bacterial adhesion, considering an initial period of biofilm formation.

13.
J Vis Exp ; (202)2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38145373

RESUMO

Hereditary diffuse gastric cancer (HDGC) caused by the CDH1 gene mutation is an inherited cancer syndrome that increases the risk of diffuse gastric cancer and is nearly impossible to detect by screening gastroscopy. The recommended preventative treatment is a total gastrectomy. Robotic surgery facilitates the use of minimally invasive surgical (MIS) techniques for anastomoses and posterior vagus preservation to potentially reduce adverse functional outcomes. An asymptomatic 24 year old male with the CDH1 gene mutation proven by genetic testing and a family history of a brother having a total gastrectomy for HDGC was treated with this technique. This video case report demonstrates the techniques and pitfalls of robotic surgery in terms of the patient positioning and port placement, posterior vagus-preserving dissection, sutured esophagojejunostomy, jejunal pouch formation, and Roux-en-Y reconstruction with a staple-stapled jejunojejunostomy. While these techniques are demonstrated in the case of prophylactic gastrectomy, many of them can be applied to other benign and bariatric foregut and general surgery types.Robotic surgery can facilitate the foregut MIS technique, as described in this case of a vagus-sparing total gastrectomy.


Assuntos
Adenocarcinoma , Procedimentos Cirúrgicos Robóticos , Neoplasias Gástricas , Humanos , Masculino , Adulto Jovem , Adenocarcinoma/etiologia , Antígenos CD/genética , Caderinas/genética , Gastrectomia/métodos , Gastroscopia , Mutação em Linhagem Germinativa , Mutação , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirurgia
14.
Clin Proteomics ; 20(1): 53, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38017436

RESUMO

BACKGROUND: Diagnosis of liver disease at earlier stages can improve outcomes and reduce the risk of progression to malignancy. Liver biopsy is the gold standard for diagnosis of liver disease, but is invasive and sample acquisition errors are common. Serum biomarkers for liver function and fibrosis, combined with patient factors, may allow for noninvasive detection of liver disease. In this pilot study, we tested and validated the performance of an algorithm that combines GP73 and LG2m serum biomarkers with age and sex (GLAS) to differentiate between patients with liver disease and healthy individuals in two independent cohorts. METHODS: To develop the algorithm, prototype immunoassays were used to measure GP73 and LG2m in residual serum samples collected between 2003 and 2016 from patients with staged fibrosis and cirrhosis of viral or non-viral etiology (n = 260) and healthy subjects (n = 133). The performance of five predictive models using combinations of age, sex, GP73, and/or LG2m from the development cohort were tested. Residual samples from a separate cohort with liver disease (fibrosis, cirrhosis, or chronic liver disease; n = 395) and healthy subjects (n = 106) were used to validate the best performing model. RESULTS: GP73 and LG2m concentrations were higher in patients with liver disease than healthy controls and higher in those with cirrhosis than fibrosis in both the development and validation cohorts. The best performing model included both GP73 and LG2m plus age and sex (GLAS algorithm), which had an AUC of 0.92 (95% CI: 0.90-0.95), a sensitivity of 88.8%, and a specificity of 75.9%. In the validation cohort, the GLAS algorithm had an estimated an AUC of 0.93 (95% CI: 0.90-0.95), a sensitivity of 91.1%, and a specificity of 80.2%. In both cohorts, the GLAS algorithm had high predictive probability for distinguishing between patients with liver disease versus healthy controls. CONCLUSIONS: GP73 and LG2m serum biomarkers, when combined with age and sex (GLAS algorithm), showed high sensitivity and specificity for detection of liver disease in two independent cohorts. The GLAS algorithm will need to be validated and refined in larger cohorts and tested in longitudinal studies for differentiating between stable versus advancing liver disease over time.

15.
Urol Oncol ; 41(11): 454.e9-454.e16, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37734979

RESUMO

BACKGROUND: There is a clinical need to identify patients with an elevated PSA who would benefit from prostate biopsy due to the presence of clinically significant prostate cancer (CSCaP). We have previously reported the development of the MiCheck® Test for clinically significant prostate cancer. Here, we report MiCheck's further development and incorporation of the Roche Cobas standard clinical chemistry analyzer. OBJECTIVES: To further develop and adapt the MiCheck® Prostate test so it can be performed using a standard clinical chemistry analyzer and characterize its performance using the MiCheck-01 clinical trial sample set. DESIGN, SETTINGS, AND PARTICIPANTS: About 358 patient samples from the MiCheck-01 US clinical trial were used for the development of the MiCheck® Prostate test. These consisted of 46 controls, 137 non-CaP, 62 non-CSCaP, and 113 CSCaP. METHODS: Serum analyte concentrations for cellular growth factors were determined using custom-made Luminex-based R&D Systems multi-analyte kits. Analytes that can also be measured using standard chemistry analyzers were examined for their ability to contribute to an algorithm with high sensitivity for the detection of clinically significant prostate cancer. Samples were then re-measured using a Roche Cobas analyzer for development of the final algorithm. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Logistic regression modeling with Monte Carlo cross-validation was used to identify Human Epidydimal Protein 4 (HE4) as an analyte able to significantly improve the algorithm specificity at 95% sensitivity. A final model was developed using analyte measurements from the Cobas analzyer. RESULTS: The MiCheck® logistic regression model was developed and consisted of PSA, %free PSA, DRE, and HE4. The model differentiated clinically significant cancer from no cancer or not-clinically significant cancer with AUC of 0.85, sensitivity of 95%, and specificity of 50%. Applying the MiCheck® test to all evaluable 358 patients from the MiCheck-01 study demonstrated that up to 50% of unnecessary biopsies could be avoided while delaying diagnosis of only 5.3% of Gleason Score (GS) ≥3+4 cancers, 1.8% of GS≥4+3 cancers and no cancers of GS 8 to 10. CONCLUSIONS: The MiCheck® Prostate test identifies clinically significant prostate cancer with high sensitivity and negative predictive value (NPV). It can be performed in a clinical laboratory using a Roche Cobas clinical chemistry analyzer. The MiCheck® Prostate test could assist in reducing unnecessary prostate biopsies with a marginal number of patients experiencing a delayed diagnosis.


Assuntos
Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/patologia , Antígeno Prostático Específico , Neoplasias da Próstata/patologia , Biópsia , Valor Preditivo dos Testes
16.
Bioconjug Chem ; 34(10): 1727-1737, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37750807

RESUMO

Glutathione S-transferase is heterogeneously expressed in breast cancer cells and is therefore emerging as a potential diagnostic biomarker for studying the heterogeneity of breast cancers. However, available fluorescent probes for GSTs depend heavily on GSTs-catalyzed glutathione (GSH) nucleophilic substitution reactions, making them susceptible to interference by the high concentration of nucleophilic species in the cellular environment. Moreover, the functions of subcellular GSTs are generally overlooked due to the lack of suitable luminescence probes. Herein, we report a highly selective affinity-based luminescence probe 1 for GST in breast cancer cells through tethering a GST inhibitor, ethacrynic acid, to an iridium(III) complex. Compared to activity-based probes which require the use of GSH, this probe could image GST-pi in the mitochondria by directly adducting to GST-pi (or potentially GST-pi/GS) in living cells. Probe 1 possesses desirable photophysical properties including a lifetime of 911 ns, a Stokes shift of 343 nm, and high photostability. The "turn on" luminescence mode of the probe enables highly selective detection of the GST with a limit of detection of 1.01 µM, while its long emission lifetime allows sensitive detection in organic dye-spiked autofluorescence samples by a time-resolved mode. The probe was further applied to specifically and quantitatively visualize MDA-MB-231 cells via specific binding to mitochondrial GST, and could differentiate breast cell lines based on their expression levels of GST. To the best of our knowledge, this probe is the first affinity-based iridium(III) imaging probe for the subcellular GST. Our work provides a valuable tool for unmasking the diverse roles of a subcellular GST in living systems, as well as for studying the heterogeneity of breast cancers.


Assuntos
Neoplasias da Mama , Glutationa Transferase , Humanos , Feminino , Glutationa Transferase/metabolismo , Neoplasias da Mama/diagnóstico por imagem , Irídio , Ácido Etacrínico , Mitocôndrias/metabolismo , Glutationa/metabolismo
17.
Anticancer Res ; 43(7): 2899-2907, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37351979

RESUMO

BACKGROUND/AIM: Pulmonary metastases are the second most common site of metastasis in colorectal cancer after the liver, and microwave ablation (MWA) for its treatment has grown in popularity in patients who are not suitable for pulmonary metastatectomy. However, its long-term efficacy remains unknown. MATERIALS AND METHODS: A systematic review was conducted in July 2022 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, using PubMed, EMBASE, Scopus, and Cochrane databases. Studies adopting MWA for colorectal cancer pulmonary metastases were included. RESULTS: A total of 488 lesions were ablated in 230 patients across eight studies. The median duration of ablation was 10 minutes. The mean length of stay in hospital was 2.3 days. Complications included pneumothorax in 128 (52%) patients; pneumonia, which occurred in 4 (1.7%) patients, and pulmonary haemorrhage in 23 (10.0%) patients. Complete remission was achieved in 85 (37.0%) patients, local control was achieved in 103 (44.8%) patients, and residual or progressive disease remained in 85 (37.0%). Survival post ablation at 1 year was 89.2% and at 3 years was 40.3%. Post-ablation disease-free survival was 43.2% at 3 years. CONCLUSION: MWA is an alternative treatment for pulmonary metastases of colorectal cancer. It has competitive theoretical properties and local recurrence rate compared to radiofrequency ablation.


Assuntos
Ablação por Cateter , Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Pulmonares , Ablação por Radiofrequência , Humanos , Resultado do Tratamento , Micro-Ondas/efeitos adversos , Ablação por Cateter/efeitos adversos , Neoplasias Pulmonares/secundário , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário
18.
Clin Proteomics ; 20(1): 25, 2023 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-37357306

RESUMO

BACKGROUND: Close to three-quarters of ovarian cancer cases are frequently diagnosed at an advanced stage, with more than 70% of them failing to respond to primary therapy and relapsing within 5 years. There is an urgent need to identify strategies for early detection of ovarian cancer recurrence, which may lead to earlier intervention and better outcomes. METHODS: A customized magnetic bead-based 8-plex immunoassay was evaluated using a Bio-Plex 200 Suspension Array System. Target protein levels were analyzed in sera from 58 patients diagnosed with advanced ovarian cancer (including 34 primary and 24 recurrent tumors) and 46 healthy controls. The clinical performance of these biomarkers was evaluated individually and in combination for their ability to detect recurrent ovarian cancer. RESULTS: An 8-plex immunoassay was evaluated with high analytical performance suitable for biomarker validation studies. Logistic regression modeling selected a two-marker panel of CA-125 and VCAM-1 that improved the performance of CA-125 alone in detecting recurrent ovarian cancer (AUC: 0.813 versus 0.700). At a fixed specificity of 83%, the two-marker panel significantly improved sensitivity in separating primary from recurrent tumors (70.8% versus 37.5%, P = 0.004), demonstrating that VCAM-1 was significantly complementary to CA-125 in detecting recurrent ovarian cancer. CONCLUSIONS: A two-marker panel of CA-125 and VCAM-1 showed strong diagnostic performance and improvement over the use of CA-125 alone in detecting recurrent ovarian cancer. The experimental results warrant further clinical validation to determine their role in the early detection of recurrent ovarian cancer.

20.
Obes Surg ; 33(7): 2005-2015, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37212965

RESUMO

PURPOSE: Revision bariatric surgery may be undertaken after weight loss failure and/or complications following primary bariatric surgery. This study aims to compare the efficacy and safety of revision laparoscopic sleeve gastrectomy (RLSG) after gastric banding (GB) to those of primary laparoscopic sleeve gastrectomy (PLSG). MATERIALS AND METHODS: A retrospective, propensity-score matched study was conducted to compare between PLSG (control) patients and RLSG after GB (treatment) patients. Patients were matched using 2:1 nearest neighbor propensity score matching without replacement. Patients were compared on weight loss outcomes and postoperative complications for up to five years. RESULTS: 144 PLSG patients were compared against 72 RLSG patients. At 36 months, PLSG patients had significantly higher mean %TWL than RLSG patients (27.4 ± 8.6 [9.3-48.9]% vs. 17.9 ± 10.2 [1.7-36.3]%, p < 0.01). At 60 months, both groups had similar mean %TWL (16.6 ± 8.1 [4.6-31.3]% vs. 16.2 ± 6.0 [8.8-22.4)]%, p > 0.05). Early functional complication rates were slightly higher with PLSG (13.9% vs. 9.7%), but late functional complication rates were comparatively higher with RLSG (50.0% vs. 37.5%). The differences were not statistically significant (p > 0.05). Both early (0.7% vs 4.2%) and late (3.5% vs 8.3%) surgical complication rates were lower in PLSG patients compared to RLSG patients but did not reach statistical significance (p > 0.05). CONCLUSION: RLSG after GB has poorer weight loss outcomes than PLSG in the short-term. Although RLSG may carry higher risks of functional complications, the safety of RLSG and PLSG are overall comparable.


Assuntos
Cirurgia Bariátrica , Derivação Gástrica , Gastroplastia , Laparoscopia , Obesidade Mórbida , Humanos , Gastroplastia/efeitos adversos , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Pontuação de Propensão , Laparoscopia/efeitos adversos , Cirurgia Bariátrica/efeitos adversos , Gastrectomia/efeitos adversos , Redução de Peso , Reoperação , Resultado do Tratamento
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