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1.
Discov Oncol ; 15(1): 252, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38954151

RESUMEN

OBJECTIVE: To evaluate the diagnostic value of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) for intracapsular prostate cancer with a poor prognosis (PPC) and no extracapsular invasion or distant metastasis. METHODS: The PET/CT images and clinical data of 221 patients were retrospectively analyzed. These patients all had clear pathological results. The maximum standard uptake value (SUVmax) of the main lesions was measured at the postprocessing workstation and was tested for correlation with the pathological score. The diagnostic accuracy was calculated using the receiver operating characteristic (ROC) curve, and the best diagnostic threshold was calculated. The correlation between SUVmax and the International Society of Urological Pathology Grade Group (GG) was also analyzed. RESULTS: The pathological results of the 221 patients were 48 benign lesions and 173 malignant lesions, including 81 PPC. Low-, intermediate-, and high-risk prostate cancers made up 21.97% (38/173), 54.33% (94/173), and 23.70% (41/173) of the malignant lesions, respectively. SUVmax and GG were positively correlated (r = 0.54, P < 0.01). The best SUVmax thresholds for 68Ga-PSMA PET/CT for the diagnosis of intracapsular PC and PPC were 7.95 and 13.94, respectively; the specificities were 0.83 and 0.85, the negative predictive values were 0.55 and 0.87, and the areas under the ROC curves were 0.88 and 0.88, respectively. CONCLUSION: 68Ga-PSMA PET/CT has high specificity and NPV in the diagnosis of intracapsular PPC, but the sensitivity for the diagnosis of intracapsular low-risk PC is low, which may cause some cases to be undetected.

2.
Front Psychiatry ; 15: 1391607, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38835553

RESUMEN

This case report describes an exceptionally rare case in which a prior diagnosis of schizophrenia was later determined to be early-onset Fahr's disease, linked to a genetic mutation in the SLC20A2 gene. Initially, the patient exhibited symptoms resembling schizophrenia, including aggression and hostility, and was highly susceptible to medication side effects such as restlessness and Parkinsonism. Despite maintaining independent activities of daily living, his neurological examinations revealed hidden weakness on the left side. Following adjustments to the medication regimen, stability was achieved with residual psychotic symptoms under treatment with Risperidone 1.5mg/day, Valproic acid 1500mg/day, and Quetiapine 37.5mg/day. This case underscores the importance of conducting comprehensive imaging studies at the time of initial psychiatric diagnosis, regardless of the apparent typicality of the presentation. Additionally, it emphasizes the need for patience and adherence to the "Start Low and Go Slow" approach in medication management to minimize the risk of exacerbating psychiatric symptoms and aggression.

3.
Clin Genitourin Cancer ; 22(3): 102086, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38697880

RESUMEN

INTRODUCTION: Men with advanced germ cell tumors (GCT) treated with chemotherapy are at high risk of venous thromboembolism (VTE). Predictors of VTE may identify patients who would benefit from prophylactic anticoagulation. PATIENTS AND METHODS: Men with advanced GCT (Stage IS, II, III) treated with chemotherapy were identified at 2 centers. High genomic risk was defined from a 5 single nucleotide polymorphism (SNP) germline panel. Logistic regression was used to evaluate the impact of genomic risk on VTE within 6 months of chemotherapy initiation. Orthogonal Projection to Latent Structures Discriminant Analysis (OPLS-DA) was used to build models to predict VTE based on clinical variables and an 86 SNP panel. RESULTS: This 123-patient cohort experienced a VTE rate of 26% with an incidence of high genomic risk of 21%. Men with high genomic risk did not have a significantly higher VTE rate (31%, 8/26) than men with low genomic risk (25%, 24/97), unadjusted OR 1.4 (95% CI 0.5-3.5, P = .54). Incorporation of clinical variables (Khorana score, N3 status and elevated LDH) resulted in adjusted OR 2.1 (95% CI 0.7-6.5, P = .18). A combined model using clinical variables and 86 SNPs performed similarly (AUC 0.77) compared to clinical variables alone (AUC 0.72). CONCLUSIONS: A previously established 5-SNP panel was not associated with VTE among patients with GCT receiving chemotherapy. However, multivariable models based on clinical variables alone warrant further validation to inform prophylactic anticoagulation strategies.


Asunto(s)
Neoplasias de Células Germinales y Embrionarias , Polimorfismo de Nucleótido Simple , Humanos , Masculino , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/genética , Adulto , Tromboembolia Venosa/genética , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Trombofilia/genética , Trombofilia/tratamiento farmacológico , Persona de Mediana Edad , Factores de Riesgo , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Adulto Joven , Incidencia , Neoplasias Testiculares/tratamiento farmacológico , Neoplasias Testiculares/genética , Predisposición Genética a la Enfermedad , Estudios Retrospectivos
4.
Langmuir ; 40(12): 6562-6570, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38470825

RESUMEN

Cross-linking with functional molecular species in polymeric carbon nitride (PCN) could offer a positive strategy that tunes its molecular structure with excellent conductivity to improve photocatalytic activity. Herein, the benzene ring-cross-linked photocatalyst is obtained via the polymerization of urea, melamine, and trimesic acid. Benzene ring-cross-linked PCN narrows the band gap and augments the push-pull effect of carriers, thus enhancing visible light harvesting and transfer easiness of photogenerated electron/hole pairs. Notably, the amount of trimesic acid was optimized during the benzene ring-cross-linked photocatalyst preparation (marked as 01T/A-CN, 02T/A-CN, and 03T/A-CN). Among them, 02T/A-CN photocatalyst achieved an excellent hydrogen production rate of 1931 µmol/h·g, which is higher than that of CN under visible light and beyond most reported. Theoretical calculations further confirmed that the introduction of benzene ring significantly reduces the band gap of PCN, bringing the delocalized electron, a longer intramolecular electron transition distance, and molecular bending. All those factors made benzene ring-cross-linked PCN with improved photocatalytic hydrogen production under visible light irradiation.

5.
Clin Neurol Neurosurg ; 238: 108191, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38422744

RESUMEN

OBJECTIVE: The objective of this study was to examine survival outcomes in 136 patients with renal cell carcinoma with metastases to the brain who were treated with radiation combined with immunotherapy or tyrosine kinase inhibitor compared to those who were treated with radiation therapy alone. METHODS: The Wake Forest Gamma Knife prospective database was searched for all patients with renal cell carcinoma brain metastases. Outcome measurements included overall survival, determined via the Kaplan-Meier Method, and cumulative incidence of local and distant failure, determined using the Fine Gray competing risks analysis with death as a competing risk for the 136 patients included. RESULTS: Overall survival for the entire population at 6 months, 12 months, and 24 months was 67%, 47% and 30%, respectively. For the TKI (non-immunotherapy-treated) population (n = 37), overall survival was 75%, 61%, and 40% at 6 months, 12 months, and 24 months, respectively. For the immunotherapy-treated population (n = 35), overall survival was 85%, 64%, and 50% at 6 months, 12 months, and 24 months, respectively. Overall survival was significantly increased for patients who received radiation with either immunotherapy or TKI (p < 0.0001). CONCLUSION: Prior series of patients with brain metastases of multiple histologies have demonstrated an improvement in the local efficacy of stereotactic radiosurgery when combined with systemic agents. We found that patients treated with targeted agents and patients treated with immunotherapy demonstrated a trend towards improvement over patients treated in the era prior to the advent of either classes of novel therapies.


Asunto(s)
Neoplasias Encefálicas , Carcinoma de Células Renales , Neoplasias Renales , Radiocirugia , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Estudios Retrospectivos , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Inmunoterapia , Radiocirugia/métodos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología
6.
World Neurosurg ; 181: e453-e458, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37865197

RESUMEN

OBJECTIVE: Imaging changes after stereotactic radiosurgery (SRS) can occur for years after treatment, although the available data on the incidence of tumor progression and adverse radiation effects (ARE) are generally limited to the first 2 years after treatment. METHODS: A single-institution retrospective review was conducted of patients who had >18 months of imaging follow-up available. Patients who had ≥1 metastatic brain lesions treated with Gamma Knife SRS were assessed for the time to radiographic progression. Those with progression ≥18 months after the initial treatment were included in the present study. The lesions that progressed were characterized as either ARE or tumor progression based on the tissue diagnosis or imaging characteristics over time. RESULTS: The cumulative incidence of delayed imaging radiographic progression was 35% at 5 years after the initial SRS. The cumulative incidence curves of the time to radiographic progression for lesions determined to be ARE and lesions determined to be tumor progression were not significantly different statistically. The cumulative incidence of delayed ARE and delayed tumor progression was 17% and 16% at 5 years, respectively. Multivariate analysis indicated that the number of metastatic brain lesions present at the initial SRS was the only factor associated with late radiographic progression. CONCLUSIONS: The timing of late radiographic progression does not differ between ARE and tumor progression. The number of metastatic brain lesions at the initial SRS is a risk factor for late radiographic progression.


Asunto(s)
Neoplasias Encefálicas , Traumatismos por Radiación , Radiocirugia , Humanos , Radiocirugia/métodos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/patología , Estudios Retrospectivos , Diagnóstico por Imagen , Traumatismos por Radiación/diagnóstico por imagen , Traumatismos por Radiación/epidemiología , Traumatismos por Radiación/etiología , Necrosis/etiología , Resultado del Tratamiento
7.
Hum Mol Genet ; 33(3): 211-223, 2024 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-37819629

RESUMEN

Duchenne muscular dystrophy (DMD) is a progressive disabling X-linked recessive disorder that causes gradual and irreversible loss of muscle, resulting in early death. The corticosteroids prednisone/prednisolone and deflazacort are used to treat DMD as the standard of care; however, only deflazacort is FDA approved for DMD. The novel atypical corticosteroid vamorolone is being investigated for treatment of DMD. We compared the pharmaceutical properties as well as the efficacy and safety of the three corticosteroids across multiple doses in the B10-mdx DMD mouse model. Pharmacokinetic studies in the mouse and evaluation of p-glycoprotein (P-gP) efflux in a cellular system demonstrated that vamorolone is not a strong P-gp substrate resulting in measurable central nervous system (CNS) exposure in the mouse. In contrast, deflazacort and prednisolone are strong P-gp substrates. All three corticosteroids showed efficacy, but also side effects at efficacious doses. After dosing mdx mice for two weeks, all three corticosteroids induced changes in gene expression in the liver and the muscle, but prednisolone and vamorolone induced more changes in the brain than did deflazacort. Both prednisolone and vamorolone induced depression-like behavior. All three corticosteroids reduced endogenous corticosterone levels, increased glucose levels, and reduced osteocalcin levels. Using micro-computed tomography, femur bone density was decreased, reaching significance with prednisolone. The results of these studies indicate that efficacious doses of vamorolone, are associated with similar side effects as seen with other corticosteroids. Further, because vamorolone is not a strong P-gp substrate, vamorolone distributes into the CNS increasing the potential CNS side-effects.


Asunto(s)
Distrofia Muscular de Duchenne , Prednisolona , Pregnadienodioles , Pregnenodionas , Animales , Ratones , Prednisolona/uso terapéutico , Microtomografía por Rayos X , Ratones Endogámicos mdx , Distrofia Muscular de Duchenne/tratamiento farmacológico , Distrofia Muscular de Duchenne/genética , Corticosterona/uso terapéutico , Preparaciones Farmacéuticas
8.
Obes Surg ; 34(1): 291-292, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37957460

RESUMEN

Endoscopic ultrasound-directed trans-gastric interventions (EDGI) using lumen apposing metal stent (LAMS) have been increasingly utilized in patients with Roux-en-Y gastric bypass surgery. We present a case of a 71-year-old woman with Roux-en-Y anatomy presenting with choledocholithiasis and enlarged retroperitoneal lymph nodes. Given inability to identify the excluded stomach on routine EUS, enteroscopy was performed with retrograde filling of the excluded stomach to allow for its localization on EUS. The patient underwent LAMS placement to create a jejuno-gastric anastomosis. Subsequently, she had an ERCP (via the LAMS) for removal of bile duct stone and an EUS with fine needle aspiration of the para-aortic lymph node (via the LAMS) confirming malignancy. The LAMS was removed after 2 weeks and the defect closed with APC and clips. An upper GI series obtained at 4 weeks did not show any residual leak. Patient continues to follow up with oncology for workup of primary malignancy.


Asunto(s)
Derivación Gástrica , Neoplasias , Obesidad Mórbida , Femenino , Humanos , Anciano , Colangiopancreatografia Retrógrada Endoscópica , Obesidad Mórbida/cirugía , Estómago/cirugía
9.
J Endourol ; 38(3): 283-289, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38149608

RESUMEN

Purpose: To evaluate the safety and feasibility of lingual mucosal graft ureteroplasty (LMGU) combined with ureteral reimplantation (UR) for repairing managing multifocal ureteral strictures (MUS). Methods: Between December 2020 and December 2022, 14 patients underwent LMGU combined with UR. Their perioperative data were collected retrospectively and analyzed. For the proximal diseased ureter, the narrow segment was incised longitudinally to open the ventral wall of ureter, and a lingual mucosal graft was placed as an onlay graft. Meanwhile, UR was applied to treat distal ureteral strictures. Results: Of 14 patients, three (21.4%) had previously undergone a failed ureteral reconstruction. The mean (standard deviation [SD]) proximal stricture length was 4.0 cm (1.56), and distal ureteral stricture length was 4.3 cm (0.94). The mean (SD) operative time was 236 minutes (57), the estimated blood loss was 78 mL (41.5), and the length of postoperative stay was 6 days. One (7%) patient underwent double LMGU to treat proximal 2 segments of ureteral stricture. No open conversions and intraoperative complications occurred. With a mean follow-up of 15 months (range 6-29), the recurrence-free rate was 14/14 (100%). Conclusions: LMGU combined with UR is a feasible and effective technique for managing MUS and can be an alternative to ileal ureteral replacement or renal autotransplantation in some selected patients with MUS.


Asunto(s)
Procedimientos de Cirugía Plástica , Uréter , Obstrucción Ureteral , Humanos , Constricción Patológica/cirugía , Estudios Retrospectivos , Uréter/cirugía , Obstrucción Ureteral/cirugía
10.
IEEE Trans Image Process ; 33: 69-81, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38032791

RESUMEN

Single image de-raining is an emerging paradigm for many outdoor computer vision applications since rain streaks can significantly degrade the visibility and render the function compromised. The introduction of deep learning (DL) has brought about substantial advancement on de-raining methods. However, most existing DL-based methods use single homogeneous network architecture to generate de-rained images in a general image restoration manner, ignoring the discrepancy between rain location detection and rain intensity estimation. We find that this discrepancy would cause feature interference and representation ability degradation problems which significantly affect de-raining performance. In this paper, we propose a novel heterogeneous de-raining architecture aiming to decouple rain location detection and rain intensity estimation (DLINet). For these two subtasks, we provide dedicated network structures according to their differential properties to meet their respective performance requirements. To coordinate the decoupled subnetworks, we develop a high-order collaborative network learning the dynamic inter-layer interactions between rain location and intensity. To effectively supervise the decoupled subnetworks during training, we propose a novel training strategy that imposes task-oriented supervision using the label learned via joint training. Extensive experiments on synthetic datasets and real-world rainy scenes demonstrate that the proposed method has great advantages over existing state-of-the-art methods.

11.
Front Public Health ; 11: 1248674, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38074723

RESUMEN

Background: Currently, there is limited research on the specific relationship between N, N-diethyl-m-toluamide (DEET) exposure and the odds of kidney stones. We aimed to investigate the relationship between DEET exposure and the prevalence of kidney stones. Methods: We included 7,567 qualified participants in our research from the 2007-2016 NHANES survey. We carried out three logistic regression models to explore the potential association between DEET exposure and the odds of kidney stones. Spline smoothing with generalized additive models (GAM) was utilized to assess the non-linear relationship and restricted cubic spline (RCS) curves was to determine the dose-response association. Multivariate regression models were used to conduct stratified analysis and sensitivity analysis. Results: Baseline characteristics of study participants presented the distribution of covariables. Regression analysis revealed that the odds of kidney stones were positively associated with the main metabolites of 3-diethyl-carbamoyl benzoic acid (DCBA) (log2) (OR = 1.05, 95% CI 1.02 to 1.08). The fourth quartile of urine DCBA showed a greater risk of kidney stones in the fully adjusted model (OR = 1.36, 95% CI 1.08 to 1.72). Another DEET metabolite of N, N-diethyl-3-hydroxymethylbenzamide (DHMB) was used to confirm the accuracy and stability of the results. The spline smoothing curve represented two main DEET metabolites had similar no-linear relationships and a positive trend with kidney stones proportion. RCS implied that the incidence of kidney stones rose with increasing levels of DEET exposure. High-risk groups on kidney stones were exhibited by stratified analysis under DEET exposure. Conclusion: Our study suggests that DEET exposure is positively associated with odds of kidney stones. Further investigation into the underlying processes of this association is required to guide the prevention and treatment of kidney stones.


Asunto(s)
Repelentes de Insectos , Cálculos Renales , Adulto , Humanos , DEET/metabolismo , Repelentes de Insectos/metabolismo , Encuestas Nutricionales , Encuestas y Cuestionarios , Cálculos Renales/inducido químicamente , Cálculos Renales/epidemiología
12.
Int J Gynecol Pathol ; 2023 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-38085960

RESUMEN

Endometrial stromal tumors (ESTs) are uncommon uterine mesenchymal lesions. Nuclear expression of ß-catenin, an indication of activated Wnt/ß-catenin signaling pathway, was described in 50% to 92% of low-grade ESTs, including endometrial stromal nodule and low-grade endometrial stromal sarcoma. Activation of the Wnt/ß-catenin signaling pathway leads to the translocation of ß-catenin into the nucleus and interaction with the T-cell factor/lymphoid enhancer-binding factor-1 (LEF1) family of transcription factors to regulate cell proliferation, differentiation, migration, and survival. Immunohistochemical analysis of ß-catenin and LEF1 was performed in 2 endometrial stromal nodules and 20 low-grade endometrial stromal sarcomas and demonstrated 90.9% and 81.8% positive rates for ß-catenin and LEF1, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of ß-catenin and LEF1 were 90.9% versus 81.8%, 81.0% versus 85.7%, 83.3% versus 85.7%, 89.5% versus 81.8%, respectively, in the diagnosis of low-grade ESTs. There is no statistical significance of the performance of ß-catenin and LEF1 in all ESTs (P = 0.664) or in primary or metastatic/recurrent settings (P = 0.515 and 0.999, respectively). Only 3 smooth muscle tumors showed focal and weak positivity for LEF1. Our results indicate LEF1 can be a useful marker in aiding a diagnosis of low-grade EST and differentiating from smooth muscle tumors alone or in combination with ß-catenin.

13.
Int J Gen Med ; 16: 6041-6049, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38148886

RESUMEN

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been recognized as a valuable biomarker for identifying the risk of cardiovascular diseases and inflammation. Furthermore, there is strong evidence to suggest that metabolic syndrome is closely associated with chronic inflammation. Accordingly, the present study endeavors to examine the potential correlation between metabolic syndrome and the levels of Lp-PLA2. Methods: To explore the relationship between Lp-PLA2 levels and metabolic syndrome, and to establish the predictive cut-off value of Lp-PLA2, a retrospective analysis was conducted using medical data from a sample of 3549 Chinese adults (comprising 2182 men and 1367 women) aged between 18 and 50 years, who had undergone health check-ups. In addition, the study also sought to investigate any potential differences in Lp-PLA2 levels based on sex and age. Results: The analysis of the data indicated that participants had a mean age of 44.2 years, a mean Lp-PLA2 level of 589 IU/L, and a metabolic syndrome prevalence of 22%. Lp-PLA2 levels were significantly different between males and females, and a significant correlation was observed between Lp-PLA2 levels and clinical and metabolic characteristics, including BMI, cholesterol, and triglycerides. Interestingly, Lp-PLA2 demonstrated potential as an indicator of metabolic syndrome, particularly in females, despite other biomarkers, such as TG/HDL-C and WHR, exhibiting better area under the curve. Conclusion: Our findings suggest that Lp-PLA2 may serve as a useful biomarker for identifying individuals at risk of developing metabolic syndrome, particularly in females. Further research is needed to explore the potential of Lp-PLA2 as a diagnostic and therapeutic target for metabolic syndrome.

15.
Front Oncol ; 13: 1214126, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38023147

RESUMEN

Background: Clinical biomarkers for brain metastases remain elusive. Increased availability of genomic profiling has brought discovery of these biomarkers to the forefront of research interests. Method: In this single institution retrospective series, 130 patients presenting with brain metastasis secondary to Non-Small Cell Lung Cancer (NSCLC) underwent comprehensive genomic profiling conducted using next generation circulating tumor deoxyribonucleic acid (DNA) (Guardant Health, Redwood City, CA). A total of 77 genetic mutation identified and correlated with nine clinical outcomes using appropriate statistical tests (general linear models, Mantel-Haenzel Chi Square test, and Cox proportional hazard regression models). For each outcome, a genetic signature composite score was created by summing the total genes wherein genes predictive of a clinically unfavorable outcome assigned a positive score, and genes with favorable clinical outcome assigned negative score. Results: Seventy-two genes appeared in at least one gene signature including: 14 genes had only unfavorable associations, 36 genes had only favorable associations, and 22 genes had mixed effects. Statistically significant associated signatures were found for the clinical endpoints of brain metastasis velocity, time to distant brain failure, lowest radiosurgery dose, extent of extracranial metastatic disease, concurrent diagnosis of brain metastasis and NSCLC, number of brain metastases at diagnosis as well as distant brain failure. Some genes were solely associated with multiple favorable or unfavorable outcomes. Conclusion: Genetic signatures were derived that showed strong associations with different clinical outcomes in NSCLC brain metastases patients. While these data remain to be validated, they may have prognostic and/or therapeutic impact in the future. Statement of translation relevance: Using Liquid biopsy in NSCLC brain metastases patients, the genetic signatures identified in this series are associated with multiple clinical outcomes particularly these ones that lead to early or more numerous metastases. These findings can be reverse-translated in laboratory studies to determine if they are part of the genetic pathway leading to brain metastasis formation.

16.
Org Lett ; 25(34): 6434-6439, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37606692

RESUMEN

A straightforward diastereo- and enantioselective Claisen rearrangement/oxa-Michael addition tandem sequence with a cinchona squaramide catalyst was described, which afforded a practical and atom-economical approach to access a range of valuable dihydropyrans in good to excellent yields with excellent stereoselectivities. The organo-bifunctional catalyst played a key role in enhancing stereoselectivity in this asymmetric tandem sequence. Moreover, the asymmetric catalytic sequential processes of the hydroalkoxylation/Claisen rearrangement/cyclization sequence and Claisen rearrangement/aza-Michael addition tandem sequence have also been afforded good yields and moderate stereoselectivities.

18.
Sci Rep ; 13(1): 11640, 2023 07 19.
Artículo en Inglés | MEDLINE | ID: mdl-37468581

RESUMEN

Peritoneal mesothelioma (PM) is a rare malignancy with poor prognosis, representing about 10-15% of all mesothelioma cases. Herein we apply PM patient-derived tumor organoids (PTOs) in elucidating personalized HIPEC responses to bypass rarity of disease in generating preclinical data. Specimens were obtained from PM patients undergoing cytoreductive surgery with HIPEC. PTOs were fabricated with tumor cells suspended in ECM-hydrogel and treated with HIPEC regimen parameters. Viability and characterization analyses were performed post-treatment. Treatment efficacy was defined as ≥ 50% viability reduction and p < 0.05 compared to controls. From October 2020 to November 2022, 17 tumors from 7 patients were biofabricated into organoids, with 16/17 (94.1%) sites undergoing comparative 37° and 42° treatments with cisplatin and mitomycin C (MMC). Hyperthermic cisplatin and MMC enhanced cytotoxicity which reduced treatment viability by 25% and 22%, respectively, compared to normothermia. Heated cisplatin displayed the greatest cytotoxicity, with efficacy in 12/16 (75%) tumors and an average viability of 38% (5-68%). Heated MMC demonstrated efficacy in 7/16 (43.8%) tumors with an average treatment viability of 51% (17-92.3%). PTOs fabricated from distinct anatomic sites exhibited site-specific variability in treatment responses. PM PTOs exhibit patient and anatomic location treatment responses suggestive of underlying disease clonality. In PM organoids cisplatin is superior to MMC in HIPEC.


Asunto(s)
Hipertermia Inducida , Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneales , Humanos , Mitomicina/uso terapéutico , Cisplatino/farmacología , Cisplatino/uso terapéutico , Quimioterapia Intraperitoneal Hipertérmica , Terapia Combinada , Mesotelioma/tratamiento farmacológico , Mesotelioma Maligno/tratamiento farmacológico , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/patología , Perfusión , Organoides/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos
19.
Nutr Res ; 117: 48-55, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37473660

RESUMEN

Vitamin D deficiency (VDD) is commonly observed in people with late-stage chronic kidney disease (CKD) and end-stage renal disease; it has also been associated with the progression of kidney disease. We hypothesized that VDD played a role in early-stage chronic kidney disease as well. Thus, this cross-sectional study aimed to evaluate the association between serum 25-hydroxyvitamin D concentration and CKD stages 1 through 3 (early-stage CKD) in a relatively healthy population in China. A total of 3142 Chinese individuals were included in this cross-sectional study. VDD was observed in 108 (5.6%) males and 307 (25.33%) females. We found a significant inverse association between serum 25(OH)D concentration with CKD stages in both sexes. Furthermore, VDD was associated with CKD stages 1 through 3 in males (adjusted odds ratio, 15.84; 95% confidence interval, 7.85-31.98; P < .001), but not in females. Vitamin D status should be evaluated in people who are newly diagnosed with CKD stages 1 through 3 or decreased estimated glomerular filtration rate, especially in males.


Asunto(s)
Insuficiencia Renal Crónica , Deficiencia de Vitamina D , Humanos , Femenino , Masculino , Caracteres Sexuales , Estudios Transversales , Factores de Riesgo , Vitamina D , Vitaminas , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiología
20.
Carcinogenesis ; 44(7): 576-586, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37452741

RESUMEN

Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism in cancer development and progression. Poly(A) binding protein nuclear 1 (PABPN1) is a gene that encodes abundant nuclear protein, binds with high affinity to nascent poly(A) tails, and is crucial for 3'-UTR (3'-untranslated region) APA. Although PABPN1 has been recently reported as a dominant master APA regulator in clear cell renal cell carcinoma (ccRCC), the underlying functional mechanism remain unclear and the genes subject to PABPN1 regulation that contribute to ccRCC progression have not been identified. Here, we found that PABPN1 is upregulated in ccRCC, and its expression is highly associated with the clinical prognosis of ccRCC patients. PABPN1 promotes ccRCC cell proliferation, migration, invasion, and exerts an influence on sphingolipid metabolism and cell cycle. Moreover, PABPN1 depletion significantly suppressed cancer cell growth via induction of cell cycle arrest and apoptosis. In particular, we characterized PABPN1-regulated 3'-UTR APA of sphingosine-1-phosphate lyase 1 (SGPL1) and cellular repressor of E1A stimulated genes 1 (CREG1), which contribute to ccRCC progression. Collectively, our data revealed that PABPN1 promotes ccRCC progression at least in part, by suppressing SGPL1 and CREG1. Thus, PABPN1 may be a potential therapeutic target in ccRCC.

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