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1.
Head Face Med ; 20(1): 33, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760840

RESUMO

BACKGROUND: Dental cone beam computed tomography (CBCT) is commonly used to evaluate cancellous bone density before dental implant surgery. However, to our knowledge, no measurement approach has been standardized yet. This study aimed to evaluate the relationship between three different regions of interest (ROI) methods on cancellous bone density at the dental implant site using dental CBCT images. METHODS: Patients' dental CBCT images (n = 300) obtained before dental implant surgery were processed using Mimics (Materialise, Leuven, Belgium). At the potential implant sites, the rectangle, cylinder, and surrounding cylinder ROI methods were used to measure bone density. Repeated measures one-way analysis of variance was performed to compare the three ROI methods in terms of measurement results. Pearson correlation analysis was performed to identify the likely pair-wise correlations between the three ROI methods. RESULTS: The density value obtained using the surrounding cylinder approach (grayscale value [GV],523.56 ± 228.03) was significantly higher than the values obtained using the rectangle (GV, 497.04 ± 236.69) and cylinder (GV,493 ± 231.19) ROI methods in terms of results. Furthermore, significant correlations were noted between the ROI methods (r > 0.965; p < 0.001). CONCLUSIONS: The density measured using the surrounding cylinder method was the highest. The choice of method may not influence the trends of measurement results. TRIAL REGISTRATION: This study was approved by the Institutional Review Board of China Medical University Hospital, No. CMUH111-REC3-205. Informed consent was waived by the Institutional Review Board of China Medical University Hospital, CMUH111-REC3-205, owing to the retrospective nature of the study.


Assuntos
Densidade Óssea , Tomografia Computadorizada de Feixe Cônico , Humanos , Tomografia Computadorizada de Feixe Cônico/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Estudos Retrospectivos , Cuidados Pré-Operatórios/métodos , Implantação Dentária/métodos , Adulto Jovem , Implantes Dentários , Implantação Dentária Endóssea/métodos
2.
Behav Processes ; 218: 105044, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38679343

RESUMO

The goal is to understand consequences of anabolic-androgenic steroid (AAS) abuse on cognitive function, using rats as a model. Economic decision making was evaluated in an operant test of effort value discounting, where subjects choose between 2 levers that deliver large and small rewards differing in maximum value and reward contrast. The hypothesis is that chronic high-dose testosterone increases preference for large rewards. Male rats were treated chronically with testosterone (7.5 mg/kg) or vehicle. Initially, all rats preferred the large reward lever when large and small rewards remained fixed at 3 and 1 sugar pellets, respectively. When different reward values were introduced, and with increasing response requirements, testosterone-treated rats made fewer responses for the large reward, and increased omissions. They earned fewer rewards overall. To determine if testosterone impairs memory, rats were tested for recognition memory with the novel object recognition and social transmission of food preference tasks, and for spatial memory with the radial arm maze and Morris water maze. There was not effect of chronic high-dose testosterone on any memory task. These results suggest that testosterone shifts economic decision making towards larger rewards even when they are disadvantageous, but does not alter memory in rats.


Assuntos
Tomada de Decisões , Recompensa , Testosterona , Animais , Masculino , Testosterona/farmacologia , Ratos , Tomada de Decisões/efeitos dos fármacos , Tomada de Decisões/fisiologia , Memória/efeitos dos fármacos , Condicionamento Operante/efeitos dos fármacos , Ratos Long-Evans
3.
Horm Behav ; 163: 105550, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38669977

RESUMO

The synthetic progestin, 17α-hydroxyprogesterone caproate (17-OHPC), is administered to pregnant individuals at risk for preterm birth and is likely transferred from mother to fetus. Yet, there is little information regarding the potential effects of 17-OHPC administration on behavioral and neural development in offspring. In rats, neonatal 17-OHPC exposure altered dopaminergic fiber distribution and density in the prelimbic medial prefrontal cortex (mPFC) in neonates and adolescents, respectively. Additionally, neonatal 17-OHPC exposure in male rats increased response omissions in a delay discounting task of impulsive decision-making. Because developmental 17-OHPC exposure has differential effects in males and females, investigating the effects of 17-OHPC on impulsive decision-making in female rats is necessary. The present study tested the effects of developmental 17-OHPC exposure (P1-P14) in a delay discounting task in which female rats chose between a small immediate reward and a larger delayed (0, 15 30, or 45 s) reward. 17-OHPC-exposed females made more omissions than controls. There was no effect of 17-OHPC on large reward preference nor on response time, and omissions were similar during both free- and forced-choice trials. The present study also aimed to investigate the neural mechanisms underlying omissions in 17-OHPC-exposed female rats. The dopamine transporter inhibitor, methylphenidate (MPH), was administered prior to delay discounting testing. MPH treatment did not reduce omissions in 17-OHPC-exposed females. If anything, MPH increased omissions in control females nearly fourfold during the longest delays. These results suggest that developmental 17-OHPC exposure increased omissions without affecting impulsivity or slowing decision-making. Furthermore, omissions may be regulated, at least in part, by dopaminergic mechanisms.

4.
J Exp Med ; 220(10)2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37432392

RESUMO

Cytokines produced in association with tumors can impair antitumor immune responses by reducing the abundance of type 1 conventional dendritic cells (cDC1), but the mechanism remains unclear. Here, we show that tumor-derived IL-6 generally reduces cDC development but selectively impairs cDC1 development in both murine and human systems through the induction of C/EBPß in the common dendritic cell progenitor (CDP). C/EBPß and NFIL3 compete for binding to sites in the Zeb2 -165 kb enhancer and support or repress Zeb2 expression, respectively. At homeostasis, pre-cDC1 specification occurs upon Nfil3 induction and consequent Zeb2 suppression. However, IL-6 strongly induces C/EBPß expression in CDPs. Importantly, the ability of IL-6 to impair cDC development is dependent on the presence of C/EBPß binding sites in the Zeb2 -165 kb enhancer, as this effect is lost in Δ1+2+3 mutant mice in which these binding sites are mutated. These results explain how tumor-associated IL-6 suppresses cDC1 development and suggest therapeutic approaches preventing abnormal C/EBPß induction in CDPs may help reestablish cDC1 development to enhance antitumor immunity.


Assuntos
Citocinas , Interleucina-6 , Humanos , Animais , Camundongos , Sítios de Ligação , Células Dendríticas , Homeostase
5.
Eur J Immunol ; 53(9): e2250201, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37424050

RESUMO

In vitro culture of bone marrow (BM) with Fms-like tyrosine kinase 3 ligand (Flt3L) is widely used to study development and function of type 1 conventional dendritic cells (cDC1). Hematopoietic stem cells (HSCs) and many progenitor populations that possess cDC1 potential in vivo do not express Flt3 and thus may not contribute to Flt3L-mediated cDC1 production in vitro. Here, we present a KitL/Flt3L protocol that recruits such HSCs and progenitors into the production of cDC1. Kit ligand (KitL) is used to expand HSCs and early progenitors lacking Flt3 expression into later stage where Flt3 is expressed. Following this initial KitL phase, a second Flt3L phase is used to support the final production of DCs. With this two-stage culture, we achieved approximately tenfold increased production of both cDC1 and cDC2 compared to Flt3L culture. cDC1 derived from this culture are similar to in vivo cDC1 in their dependence on IRF8, ability to produce IL-12, and induction of tumor regression in cDC1-deficient tumor-bearing mice. This KitL/Flt3L system for cDC1 production will be useful in further analysis of cDC1 that rely on in vitro generation from BM.


Assuntos
Células-Tronco Hematopoéticas , Fator de Células-Tronco , Camundongos , Animais , Medula Óssea , Células da Medula Óssea , Células Dendríticas
6.
Cancer Immunol Immunother ; 72(8): 2813-2827, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37179276

RESUMO

Neoantigen burden and CD8 T cell infiltrate are associated with clinical outcome in pancreatic ductal adenocarcinoma (PDAC). A shortcoming of many genetic models of PDAC is the lack of neoantigen burden and limited T cell infiltrate. The goal of the present study was to develop clinically relevant models of PDAC by inducing cancer neoantigens in KP2, a cell line derived from the KPC model of PDAC. KP2 was treated with oxaliplatin and olaparib (OXPARPi), and a resistant cell line was subsequently cloned to generate multiple genetically distinct cell lines (KP2-OXPARPi clones). Clones A and E are sensitive to immune checkpoint inhibition (ICI), exhibit relatively high T cell infiltration, and have significant upregulation of genes involved in antigen presentation, T cell differentiation, and chemokine signaling pathways. Clone B is resistant to ICI and is similar to the parental KP2 cell line in terms of relatively low T cell infiltration and no upregulation of genes involved in the pathways noted above. Tumor/normal exome sequencing and in silico neoantigen prediction confirms successful generation of cancer neoantigens in the KP2-OXPARPi clones and the relative lack of cancer neoantigens in the parental KP2 cell line. Neoantigen vaccine experiments demonstrate that a subset of candidate neoantigens are immunogenic and neoantigen synthetic long peptide vaccines can restrain Clone E tumor growth. Compared to existing models, the KP2-OXPARPi clones better capture the diverse immunobiology of human PDAC and may serve as models for future investigations in cancer immunotherapies and strategies targeting cancer neoantigens in PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Antígenos de Neoplasias , Neoplasias Pancreáticas/terapia , Linfócitos T CD8-Positivos , Carcinoma Ductal Pancreático/terapia , Imunoterapia , Neoplasias Pancreáticas
7.
Curr Opin Ophthalmol ; 34(2): 146-151, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36730753

RESUMO

PURPOSE OF REVIEW: To critically summarize and examine published data from randomized controlled clinical trials (RCTs) investigating the safety and efficacy of microinvasive glaucoma surgeries (MIGS) with and without cataract surgery versus cataract surgery alone. RECENT FINDINGS: Three RCTs with standardized outcomes and rigorous methodology demonstrate superiority of the iStent (Glaukos), CyPass (Alcon), and Hydrus (Alcon) MIGS devices in combination with cataract surgery versus cataract surgery alone. The trials all involved medication washouts at baseline and also after 24 months of follow-up. In each of the trials, a greater proportion of participants randomized to the combined MIGS procedures achieved at least 20% unmedicated intraocular pressure (IOP) lowering compared with cataract surgery alone. With the exception of the CyPass device, which has been voluntarily withdrawn from the market, adverse events associated with MIGS were acceptable and consistent with routine intraocular surgeries. Follow-up studies demonstrate sustained efficacy, greater probabilities of visual field preservation, increased cost-effectiveness, and enhanced quality of life associated with MIGS procedures. SUMMARY: Data related to MIGS platforms for treatment of open-angle glaucoma with or without co-existing cataract supports their continued adoption in clinical practice. Future studies comparing various techniques and devices in a standardized fashion are needed.


Assuntos
Extração de Catarata , Catarata , Glaucoma de Ângulo Aberto , Facoemulsificação , Humanos , Facoemulsificação/métodos , Glaucoma de Ângulo Aberto/cirurgia , Pressão Intraocular , Catarata/complicações , Stents , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Front Immunol ; 13: 1039226, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36569934

RESUMO

Background: Cancer neoantigens are important targets of cancer immunotherapy and neoantigen vaccines are currently in development in pancreatic ductal adenocarcinoma (PDAC) and other cancer types. Immune regulatory mechanisms in pancreatic cancer may limit the efficacy of neoantigen vaccines. Targeting immune checkpoint signaling pathways in PDAC may improve the efficacy of neoantigen vaccines. Methods: We used KPC4580P, an established model of PDAC, to test whether neoantigen vaccines can generate therapeutic efficacy against PDAC. We focused on two immunogenic neoantigens associated with genetic alterations in the CAR12 and CDK12 genes. We tested a neoantigen vaccine comprised of two 20-mer synthetic long peptides and poly IC, a Toll-like receptor (TLR) agonist. We investigated the ability of neoantigen vaccine alone, or in combination with PD-1 and TIGIT signaling blockade to impact tumor growth. We also assessed the impact of TIGIT signaling on T cell responses in human PDAC. Results: Neoantigen vaccines induce neoantigen-specific T cell responses in tumor-bearing mice and slow KPC4580P tumor growth. However, KPC4580P tumors express high levels of PD-L1 and the TIGIT ligand, CD155. A subset of neoantigen-specific T cells in KPC4580P tumors are dysfunctional, and express high levels of TIGIT. PD-1 and TIGIT signaling blockade in vivo reverses T cell dysfunction and enhances neoantigen vaccine-induced T cell responses and tumor regression. In human translational studies, TIGIT signaling blockade in vitro enhances neoantigen-specific T cell function following vaccination. Conclusions: Taken together, preclinical and human translational studies support testing neoantigen vaccines in combination with therapies targeting the PD-1 and TIGIT signaling pathways in patients with PDAC.


Assuntos
Vacinas Anticâncer , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Camundongos , Animais , Receptor de Morte Celular Programada 1 , Antígenos de Neoplasias , Neoplasias Pancreáticas/genética , Carcinoma Ductal Pancreático/genética , Peptídeos/uso terapêutico , Receptores Imunológicos/uso terapêutico , Neoplasias Pancreáticas
9.
Am Surg ; : 31348221146973, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36537729

RESUMO

BACKGROUND: In adhesive small bowel obstructions (ASBOs), literature has shown that passage of a water-soluble contrast challenge at either 8 hours or 24 hours is predictive of successful non-operative management (NOM) for an ASBO, but the long-term outcomes between these two groups are unknown. We hypothesized that patients who require longer transit times to the colon have a higher one-year recidivism of ASBO. METHODS: This was a 4-year review of patients with presumed ASBO undergoing successful NOM. Those requiring operation or those with an SBO due to something other than adhesions were excluded. Patients were divided into two groups (8 hour and 24 hour) based on when contrast reached their right colon. Patients were followed for one year to determine ASBO recurrence. RESULTS: 137 patients underwent NOM; 112 in the 8-hour group and 25 in the 24-hour group. One-year recurrence rate was 21.4% in the 8-hour group and 40% in the 24-hour group (P = 0.05). The median time to recurrence was 113 days in the 8-hour group and 13 days in the 24-hour group (P = 0.02). Of those who recurred in the 24-hour group, 60% recurred within 30 days (P = 0.01). On univariable analysis, first-time ASBO and 24-hour transit time were risk factors for recurrence. CONCLUSIONS: Adhesive small bowel obstruction patients undergoing NOM in the 24-hour group had a recurrence rate nearly twice that of patients in the 8-hour group and may benefit from an operative exploration during the index hospitalization at the 8-hour mark of a water-soluble contrast challenge, especially if experiencing a first-time ASBO.

10.
Br J Oral Maxillofac Surg ; 60(9): 1209-1215, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35902310

RESUMO

The aims of this paper were to evaluate the relation between the preoperative primary tumour maximum standardised uptake value (SUVmax, tSUVmax) and clinicopathological features, including depth of invasion (DOI), recurrence factors, and survival outcomes, and to compare the prognostic value of tSUVmax with that of other factors associated with the recurrence of early-stage oral squamous cell carcinoma (OSCC) of the tongue. We retrospectively analysed data from 155 patients. All patients were treated and regularly monitored at the Changhua Christian Hospital (CCH). Only those who had undergone 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the 14 days before surgery were included. A tSUVmax of >5.2 was found to be the sole strong predictor of a DOI of >4 mm. A tSUVmax of >7.6 was strongly associated with pT2 SCC of the tongue, more aggressive DOI, and perineural invasion. DOI and tSUVmax could be used to predict disease-free survival (DFS) for early-stage SCC of the tongue, and they showed stronger predictive power than the traditional American Joint Committee on Cancer (AJCC) T stage. Therefore tSUVmax could be a prognostic tool for DFS in AJCC early-stage SCC of the tongue.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/cirurgia , Fluordesoxiglucose F18 , Prognóstico , Estudos Retrospectivos , Língua/patologia , Compostos Radiofarmacêuticos
11.
Medicine (Baltimore) ; 101(19): e29285, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35583539

RESUMO

INTRODUCTION: Primary surgical treatment for oral squamous cell carcinoma (OSCC) is reserved for T1 to T4a tumors, but not for T4b tumors, according to the present National Comprehensive Cancer Network clinical practice guidelines. In this retrospective study, we aimed to determine the association between the clinicopathological characteristics and different treatment modalities for T4b OSCC based on whether patients received primary surgical treatment. Therefore, we conducted a survival analysis based on different treatment modalities. METHODS: This retrospective cohort study enrolled 125 patients with clinical stage T4b OSCC who received treatment and were followed up at Changhua Christian Hospital between January 1, 2008 and December 31, 2018. RESULTS: Overall, 81 patients received primary surgical treatment and 44 received primary nonsurgical treatment. Comparison of the clinicopathological characteristics between those who did and did not undergo surgery revealed no significant differences in age at tumor diagnosis, tumor location, clinical N stage, and involved tumor area based on computed tomography or magnetic resonance imaging, or stratified Charlson Comorbidity Index scores. In the survival analysis, Kaplan-Meier curves revealed that patients who received treatment modalities including surgery exhibited better survival than those who received treatment modalities that did not include surgery. CONCLUSIONS: In the present study, patients with T4b OSCC treated with primary surgery had a better overall survival rate than those who received nonsurgical treatment. In the future, it will be necessary for clinicians worldwide to report the treatment outcomes of patients with T4b OSCC based on the common criteria.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
12.
Bioeng Transl Med ; 6(3): e10234, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34589606

RESUMO

Recent studies indicate that umbilical cord stem cells are cytoprotective against several disorders. One critical limitation in using stem cells is reduction in their viability under stressful conditions, such as diabetes. However, the molecular intricacies responsible for diabetic conditions are not fully elucidated. In this study, we found that high glucose (HG) conditions induced loss of chaperone homeostasis, stabilized PTEN, triggered the downstream signaling cascade, and induced apoptosis and oxidative stress in Wharton's jelly derived mesenchymal stem cells (WJMSCs). Increased Carboxyl terminus of Hsc70 interacting protein (CHIP) expression promoted phosphatase and tensin homolog (PTEN) degradation via the ubiquitin-proteasome system and shortened its half-life during HG stress. Docking studies confirmed the interaction of CHIP with PTEN and FOXO3a with the Bim promoter region. Further, it was found that the chaperone system is involved in CHIP-mediated PTEN proteasomal degradation. CHIP depletion stabilizes PTEN whereas PTEN inhibition showed an inverse effect. CHIP overactivation suppressed the binding of FOXO3a with bim. Coculturing CHIP overexpressed WJMSCs suppressed HG-induced apoptosis and oxidative stress in embryo derived cardiac cell lines. CHIP overexpressing and PTEN silenced WJMSCs ameliorated diabetic effects in streptozotocin (STZ) induced diabetic rats and further improved their body weight and heart weight, and rescued from hyperglycemia-induced cardiac injury. Considering these, the current study suggests that CHIP confers resistance to apoptosis and acts as a potentiation factor in WJMSCs to provide protection from degenerative effects of diabetes.

13.
Sci Rep ; 11(1): 15446, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34326432

RESUMO

The incidence of oral cavity squamous cell carcinoma (OSCC) is particularly high in South Asia. According to the National Comprehensive Cancer Network, OSCC can arise in several subsites. We investigated survival rates and the clinical and pathological characteristics of OSCC in different anatomical subsites in the Taiwanese population. We retrospectively analyzed data for 3010 patients with OSCC treated at the Changhua Christian Hospital. Subsequently, we compared clinical and pathological features of OSCC in different subsites. Pathological T4 stage OSCCs occurred in the alveolar ridge and retromolar trigone in 56.4% and 43.7% of cases, respectively. More than 25% of patients with tongue OSCC and 23.4% of those with retromolar OSCC had lymph node metastasis. The prognosis was worst for hard palate OSCC (hazard ratio 1.848; p < 0.001) and alveolar ridge OSCC (hazard ratio 1.220; p = 0.017). Retromolar OSCC recurred most often and tongue OSCC second most often. The risk for cancer-related mortality was highest for hard palate OSCC, followed by alveolar ridge and retromolar OSCC. We found distinct differences in survival among the different subsites of OSCC. Our findings may also help prompt future investigations of OSCC in different subsites in Taiwanese patients.


Assuntos
Processo Alveolar/patologia , Neoplasias Labiais/mortalidade , Mucosa Bucal/patologia , Neoplasias Palatinas/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Neoplasias da Língua/mortalidade , Adulto , Idoso , Feminino , Seguimentos , Humanos , Neoplasias Labiais/epidemiologia , Neoplasias Labiais/patologia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Palatinas/epidemiologia , Neoplasias Palatinas/patologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Taxa de Sobrevida , Taiwan/epidemiologia , Neoplasias da Língua/epidemiologia , Neoplasias da Língua/patologia
14.
Sci Rep ; 11(1): 15153, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312436

RESUMO

18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) is widely used for tumor staging. This study sought to determine the relationship of preoperative primary tumor SUVmax (tSUVmax) with the clinicopathological features of patients with OSCC and to compare the prognostic ability of tSUVmax with that of other recurrence factors. Data of 340 patients with OSCC who were diagnosed, treated, and followed up at the Changhua Christian Hospital were retrospectively analyzed. Only patients with OSCC arising from gingiva, palate, floor of the mouth, and retromolar trigone and those who had received preoperative FDG-PET within 2 weeks before surgery were included. tSUVmax value > 9.2 was the strong predictor of bone invasion (area under the receiver operating characteristic curve, 0.844). tSUVmax value > 7.2 showed a strong association with advanced pathological T stage and recurrence factors and was associated with poor survival; tSUVmax > 7.2 showed stronger predictive power for poor disease-free survival (DFS) than pT stage and the other recurrence factors related to primary tumor. FDG-PET can be a useful supplement to contrast-enhanced computed tomography or contrast-enhanced magnetic resonance imaging for diagnosing bone invasion by OSCC. The tSUVmax value was an independent predictor of DFS in this study.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Neoplasias Bucais/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Adulto , Idoso , Neoplasias Ósseas/mortalidade , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Fluordesoxiglucose F18 , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Invasividade Neoplásica/diagnóstico por imagem , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Tomografia por Emissão de Pósitrons , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Taiwan/epidemiologia
15.
Front Surg ; 8: 626143, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33959629

RESUMO

Patients often opt for implantation of testicular prostheses following orchidectomy for cancer or torsion. Recipients of testicular prostheses report issues regarding firmness, shape, size, and position, aspects of which relate to current limitations of silicone materials used and manufacturing methods for soft prostheses. We aim to create a 3D printable testicular prosthesis which mimics the natural shape and stiffness of a human testicle using a lattice infill structure. Porous testicular prostheses were engineered with relative densities from 0.1 to 0.9 using a repeating cubic unit cell lattice inside an anatomically accurate testicle 3D model. These models were printed using a multi-jetting process with an elastomeric material and compared with current market prostheses using shore hardness tests. Additionally, standard sized porous specimens were printed for compression testing to verify and match the stiffness to human testicle elastic modulus (E-modulus) values from literature. The resulting 3D printed testicular prosthesis of relative density between 0.3 and 0.4 successfully achieved a reduction of its bulk compressive E-modulus from 360 KPa to a human testicle at 28 Kpa. Additionally, this is the first study to quantitatively show that current commercial testicular prostheses are too firm compared to native tissue. 3D printing allows us to create metamaterials that match the properties of human tissue to create customisable patient specific prostheses. This method expands the use cases for existing biomaterials by tuning their properties and could be applied to other implants mimicking native tissues.

16.
Artigo em Inglês | MEDLINE | ID: mdl-34040436

RESUMO

Axillary lymph nodes have long been recognized as a route for breast cancer to spread systemically. As a result, staging of the axilla has always played a central role in the treatment of breast cancer. Anatomic staging was believed to be important for two reasons: 1) it predicts prognosis and guides medical therapy, and 2) it is a potential therapy for removal of disease in the axilla. This paradigm has now been called into question. Prognostic information is driven increasingly by tumor biology, and trials such as the ACOSOG Z0011 demonstrates removal of axillary disease is not therapeutic. Staging of the axilla has undergone a dramatic de-escalation; however, sentinel lymph node biopsy (SLNB) is still an invasive surgery and represents a large economic burden on the healthcare system. In this review, we outline the changing paradigms of axillary staging in breast cancer from emphasis on anatomic staging to tumor biology, and the evolving role of axillary ultrasound, bringing patients less invasive and more personalized therapy.

17.
Expert Rev Vaccines ; 20(7): 827-837, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34047245

RESUMO

Introduction: Cancer neoantigens represent important targets of cancer immunotherapy. The goal of cancer neoantigen vaccines is to induce neoantigen-specific immune responses and antitumor immunity while minimizing the potential for autoimmune toxicity. Advances in sequencing technologies, neoantigen prediction algorithms, and other technologies have dramatically improved the ability to identify and prioritize cancer neoantigens. Unfortunately, results from preclinical studies and early phase clinical trials highlight important challenges to the successful clinical translation of neoantigen cancer vaccines.Areas covered: In this review, we provide an overview of current strategies for the identification and prioritization of cancer neoantigens with a particular emphasis on the two most common strategies used for neoantigen identification: (1) direct identification of peptide ligands eluted from peptide-MHC complexes, and (2) next-generation sequencing combined with neoantigen prediction algorithms. We highlight the limitations of current neoantigen prediction pipelines, and discuss broader challenges associated with cancer neoantigen vaccines including tumor purity/heterogeneity and the immunosuppressive tumor microenvironment.Expert opinion: Despite current limitations, neoantigen prediction is likely to improve rapidly based on advances in sequencing, machine learning, and information sharing. The successful development of robust cancer neoantigen prediction strategies is likely to have a significant impact, with the potential to facilitate cancer neoantigen vaccine design.


Assuntos
Vacinas Anticâncer , Neoplasias , Antígenos de Neoplasias , Humanos , Imunoterapia/métodos , Microambiente Tumoral
18.
J Digit Imaging ; 34(2): 351-356, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33564999

RESUMO

Small renal masses are commonly diagnosed with modern medical imaging. Renal tumour volume has been explored as a prognostic tool to help decide when intervention is needed and appears to provide additional prognostic information for smaller tumours compared with tumour diameter. However, the current method of calculating tumour volume in clinical practice uses the ellipsoid equation (π/6 × length × width × height) which is an oversimplified approach. Some research groups trace the contour of the tumour in every image slice which is impractical for clinical use. In this study, we demonstrate a method of using 3D segmentation software and the 3D interpolation method to rapidly calculate renal tumour volume in under a minute. Using this method in 27 patients that underwent radical or partial nephrectomy, we found a 10.07% mean absolute difference compared with the traditional ellipsoid method. Our segmentation volume was closer to the calculated histopathological tumour volume than the traditional method (p = 0.03) with higher Lin's concordance correlation coefficient (0.79 vs 0.72). 3D segmentation has many uses related to 3D printing and modelling and is becoming increasingly common. Calculation of tumour volume is one additional benefit it provides. Further studies on the association between segmented tumour volume and prognosis are needed.


Assuntos
Neoplasias Renais , Humanos , Rim/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Software , Carga Tumoral
19.
Clin Imaging ; 75: 75-82, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33508754

RESUMO

PURPOSE: Our purpose was to conduct a comprehensive systematic review of all existing literature regarding imaging findings on chest CT and associated clinical features in pregnant patients diagnosed with COVID-19. MATERIALS & METHODS: A literature search was conducted on April 21, 2020 and updated on July 24, 2020 using PubMed, Embase, World Health Organization, and Google Scholar databases. Only studies which described chest CT findings of COVID-19 in pregnant patients were included for analysis. RESULTS: A total of 67 articles and 427 pregnant patients diagnosed with COVID-19 were analyzed. The most frequently encountered pulmonary findings on chest CT were ground-glass opacities (77.2%, 250/324), posterior lung involvement (72.5%, 50/69), multilobar involvement (71.8%, 239/333), bilateral lung involvement (69.4%, 231/333), peripheral distribution (68.1%, 98/144), and consolidation (40.9%, 94/230). Pregnant patients were also found to present more frequently with consolidation (40.9% vs. 21.0-31.8%) and pleural effusion (30.0% vs. 5.0%) in comparison to the general population. Associated clinical features included antepartum fever (198 cases), lymphopenia (128 cases), and neutrophilia (97 cases). Of the 251 neonates delivered, 96.8% had negative RT-PCR and/or IgG antibody testing for COVID-19. In the eight cases (3.2%) of reported neonatal infection, tests were either conducted on samples collected up to 72 h after birth or were found negative on all subsequent RT-PCR tests. CONCLUSION: Pregnant patients appear to present more commonly with more advanced COVID-19 CT findings compared to the general adult population. Furthermore, characteristic laboratory abnormalities found in pregnant patients tended to mirror those found in the general patient population. Lastly, results from neonatal testing suggest a low risk of vertical transmission.


Assuntos
COVID-19 , Pneumopatias , Adulto , Teste para COVID-19 , Feminino , Humanos , Recém-Nascido , Pulmão , Gravidez , SARS-CoV-2 , Tomografia Computadorizada por Raios X
20.
Cancer Med ; 9(19): 7172-7182, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32810385

RESUMO

BACKGROUND: There is increasing research in using segmentation of prostate cancer to create a digital 3D model from magnetic resonance imaging (MRI) scans for purposes of education or surgical planning. However, the variation in segmentation of prostate cancer among users and potential inaccuracy has not been studied. METHODS: Four consultant radiologists, four consultant urologists, four urology trainees, and four nonclinician segmentation scientists were asked to segment a single slice of a lateral T3 prostate tumor on MRI ("Prostate 1"), an anterior zone prostate tumor MRI ("Prostate 2"), and a kidney tumor computed tomography (CT) scan ("Kidney"). Time taken and self-rated subjective accuracy out of a maximum score of 10 were recorded. Root mean square error, Dice coefficient, Matthews correlation coefficient, Jaccard index, specificity, and sensitivity were calculated using the radiologists as the ground truth. RESULTS: There was high variance among the radiologists in segmentation of Prostate 1 and 2 tumors with mean Dice coefficients of 0.81 and 0.58, respectively, compared to 0.96 for the kidney tumor. Urologists and urology trainees had similar accuracy, while nonclinicians had the lowest accuracy scores for Prostate 1 and 2 tumors (0.60 and 0.47) but similar for kidney tumor (0.95). Mean sensitivity in Prostate 1 (0.63) and Prostate 2 (0.61) was lower than specificity (0.92 and 0.93) suggesting under-segmentation of tumors in the non-radiologist groups. Participants spent less time on the kidney tumor segmentation and self-rated accuracy was higher than both prostate tumors. CONCLUSION: Segmentation of prostate cancers is more difficult than other anatomy such as kidney tumors. Less experienced participants appear to under-segment models and underestimate the size of prostate tumors. Segmentation of prostate cancer is highly variable even among radiologists, and 3D modeling for clinical use must be performed with caution. Further work to develop a methodology to maximize segmentation accuracy is needed.


Assuntos
Imagem de Difusão por Ressonância Magnética , Neoplasias da Próstata/diagnóstico por imagem , Radiologistas , Pesquisadores , Urologistas , Humanos , Imageamento Tridimensional , Masculino , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Carga Tumoral
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