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1.
Gland Surg ; 13(2): 265-273, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38455350

RESUMO

Background: While track recurrence of thyroid cancer following endoscopic and robotic transaxillary surgeries has been reported previously, no such cases have been reported for transoral endoscopic thyroidectomy vestibular approach (TOETVA). This case report describes the first documented case of recurrence of thyroid cancer along the surgical track after TOETVA. Case Description: The patient underwent right lobectomy via TOETVA for a 4 cm follicular thyroid carcinoma (FTC) initially diagnosed as benign follicular nodule on preoperative gun biopsy. The thyroid capsule partially ruptured within the surgical field during surgery. Ultrasonography and computed tomography conducted 27 months after surgery revealed seeding recurrence in the postsurgical thyroid bed, and subcutaneous layers of the right lower lip, submental area, and mid to right upper neck levels I, IIA, and VI. Two-stage re-operation was done to perform completion thyroidectomy, lymph node dissection, and excision of recurrent nodules, which were pathologically confirmed as metastatic FTC. The patient underwent two treatments of radioactive iodine therapy, and post-therapeutic whole-body scintigraphy and computed tomography showed no residual disease. Conclusions: Careful monitoring after TOETVA is essential due to the rare but potential risk of seeding recurrence, especially when the thyroid gland ruptures during surgery. Surgeons should be aware of this atypical complication and be prepared to recommend surgical and/or medical strategies to manage any local seeding of thyroid tissue that may occur.

2.
J Pathol Transl Med ; 58(2): 59-71, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38247153

RESUMO

BACKGROUND: The classification of nodal peripheral T-cell lymphoma (PTCL) has evolved according to histology, cell-of-origin, and genetic alterations. However, the comprehensive expression pattern of follicular helper T-cell (Tfh) markers, T-cell factor-1 (TCF1), and Th1- and Th2-like molecules in nodal PTCL is unclear. METHODS: Eighty-two cases of nodal PTCL were classified into 53 angioimmunoblastic T-cell lymphomas (AITLs)/nodal T-follicular helper cell lymphoma (nTFHL)-AI, 18 PTCLs-Tfh/nTFHL-not otherwise specified (NOS), and 11 PTCLs-NOS according to the revised 4th/5th World Health Organization classifications. Immunohistochemistry for TCF1, TBX21, CXCR3, GATA3, and CCR4 was performed. RESULTS: TCF1 was highly expressed in up to 68% of patients with nTFHL but also in 44% of patients with PTCL-NOS (p > .05). CXCR3 expression was higher in AITLs than in non-AITLs (p = .035), whereas GATA3 expression was higher in non-AITL than in AITL (p = .007) and in PTCL-Tfh compared to AITL (p = .010). Of the cases, 70% of AITL, 44% of PTCLTfh/ nTFHL-NOS, and 36% of PTCL-NOS were subclassified as the TBX21 subtype; and 15% of AITL, 38% of PTCL-Tfh/nTFHL-NOS, and 36% of PTCL-NOS were subclassified as the GATA3 subtype. The others were an unclassified subtype. CCR4 expression was associated with poor progression-free survival (PFS) in patients with PTCL-Tfh (p < .001) and nTFHL (p = .023). The GATA3 subtype showed poor overall survival in PTCL-NOS compared to TBX21 (p = .046) and tended to be associated with poor PFS in patients with non-AITL (p = .054). CONCLUSIONS: The TBX21 subtype was more prevalent than the GATA3 subtype in AITL. The GATA3 subtype was associated with poor prognosis in patients with non-AITL and PTCL-NOS.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38015621

RESUMO

Achieving effective mRNA expression in vivo requires careful selection of an appropriate delivery vehicle and route of administration. Among the various routes of administration, intranasal administration has received considerable attention due to its ability to induce potent immune responses. In this context, we designed a specialized cationic polymer tailored for delivery of mRNA into the nasal cavity. These polymers are designed with varying degrees of substitution in different amine groups to allow for identification of the most suitable amine moiety for effective mRNA delivery. We also incorporated a photosensitizer within the polymer structure that can trigger the generation of reactive oxygen species when exposed to light. The synthesized cationic polymer is complexed with anionic mRNA to form a polyplex. Illuminating these polyplexes with laser light enhances their escape from intracellular endosomes, stimulating mRNA translocation into the cytoplasm, followed by increased mRNA expression at the cellular level. Through intranasal administration to C57BL/6 mice, it was confirmed that these photoactive polyplexes effectively induce mRNA expression and activate immune responses in vivo using photochemical effects. This innovative design of a photoactivated cationic polymer presents a promising and reliable strategy to achieve efficient intranasal mRNA delivery. This approach has potential applications in the development of mRNA-based vaccines for both prophylactic and therapeutic purposes.

4.
Medicine (Baltimore) ; 102(30): e34539, 2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37505160

RESUMO

The number of hospital visits with cervical cancer as the chief complaint among South Korean women aged 20 to 39 has increased by 1.2 times between 2016 and 2020, indicating a need for active screening for the disease. This study aimed to investigate the status of the Papanicolaou (Pap) test and identify factors influencing Pap test experience among South Korean women aged 20 to 39 years. An online questionnaire survey was conducted over 5 days starting from November 19, 2021. A total of 338 participants who were randomly sampled by age completed the survey. Data were analyzed using descriptive statistics, t test, χ2 test, and logistic regression. The mean age of the participants was 29.9 years, and participants with and without Pap test experience accounted for 60.7% and 39.3% of the total, respectively. There were significant differences in age, marital status, employment status, smoking status, experience of coitus, awareness of the National Cancer Screening Program, and human papillomavirus (HPV) vaccination status according to the Pap test experience (P < .05) of the participants. Pap test attitude, Pap test self-efficacy, cervical cancer knowledge, HPV knowledge, and cancer prevention behavior scores were significantly higher in the Pap test experience group than in the no Pap test experience group (P < .05). Logistic regression analysis showed that experience of coitus (odds ratio [OR] = 10.46, 95% confidence interval [CI]: 4.54-24.11), marital status (OR = 5.96, 95% CI: 2.25-15.77), awareness of the National Cancer Screening Program (OR = 4.39, 95% CI: 1.66-11.58), HPV vaccination (OR = 2.62, 95% CI: 1.35-5.09), employment status (OR = 2.22, 95% CI: 1.08-4.59), and self-efficacy (OR = 1.09, 95% CI: 1.01-1.19) were the influencing factors in the Pap test experience group. To improve the Pap test screening rate among South Korean women aged 20 to 39, reinforcement strategies and intervention programs that involve age-specific approaches must be established.


Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Adulto , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Detecção Precoce de Câncer , Teste de Papanicolaou , Conhecimentos, Atitudes e Prática em Saúde , Programas de Rastreamento , República da Coreia/epidemiologia , Esfregaço Vaginal
5.
Sci Rep ; 13(1): 1360, 2023 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-36693894

RESUMO

Neural network models have been used to analyze thyroid ultrasound (US) images and stratify malignancy risk of the thyroid nodules. We investigated the optimal neural network condition for thyroid US image analysis. We compared scratch and transfer learning models, performed stress tests in 10% increments, and compared the performance of three threshold values. All validation results indicated superiority of the transfer learning model over the scratch model. Stress test indicated that training the algorithm using 3902 images (70%) resulted in a performance which was similar to the full dataset (5575). Threshold 0.3 yielded high sensitivity (1% false negative) and low specificity (72% false positive), while 0.7 gave low sensitivity (22% false negative) and high specificity (23% false positive). Here we showed that transfer learning was more effective than scratch learning in terms of area under curve, sensitivity, specificity and negative/positive predictive value, that about 3900 images were minimally required to demonstrate an acceptable performance, and that algorithm performance can be customized according to the population characteristics by adjusting threshold value.


Assuntos
Redes Neurais de Computação , Nódulo da Glândula Tireoide , Humanos , Sensibilidade e Especificidade , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Valor Preditivo dos Testes , Ultrassonografia/métodos
6.
Eur J Cancer ; 174: 10-20, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35970031

RESUMO

BACKGROUND: T-cell factor 1 (TCF1)+Programmed cell death-1 (PD-1)+ tumour-infiltrating lymphocytes (TILs) are a recently defined subset of exhausted T-cells (Texh-cells) that exhibit a progenitor phenotype. They have been associated with a response to immune checkpoint inhibitor (ICI) therapy in murine tumour models and in patients with malignant melanoma. We investigated the significance of TCF1+PD-1+ TILs as a predictive biomarker for ICI therapy response in non-small-cell lung cancer (NSCLC). METHODS: Two different cohorts of NSCLC patients treated with ICI targeting the PD-1/PD-L1 pathway were included. RNA-seq was performed using NSCLC tissues obtained from 234 patients prior to immunotherapy (RNA-seq cohort). Double immunostaining of TCF1 and PD-1 and single immunostaining of other immunologic markers were performed in resected tumour tissues from another 116 patients (immunohistochemistry cohort). RESULTS: In the RNA-seq cohort, both Texh-cell and progenitor Texh-cell gene sets were enriched in responders compared with non-responders. Larger Texh-cell fractions and increased progenitor Texh-cell gene sets were significantly associated with better progression-free survival (PFS). In the immunohistochemistry cohort, the TCF1+PD-1+ TIL number and PD-L1 tumour proportion score were significantly higher in responders than in non-responders. A high number of TCF1+PD-1+ TILs was significantly associated with both PFS and overall survival (OS) after ICI therapy, and it independently predicted a better PFS and OS according to multivariate analysis. CONCLUSION: TCF1+PD-1+ TILs, representing progenitor Texh-cells, predict both better response and survival in NSCLC patients after ICI therapy. Thus, they may be a useful predictive biomarker for ICI therapy in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos , Carcinoma Pulmonar de Células não Pequenas/patologia , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/patologia , Linfócitos do Interstício Tumoral , Camundongos , Receptor de Morte Celular Programada 1/metabolismo
7.
Korean J Fam Med ; 43(4): 225-230, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35903045

RESUMO

BACKGROUND: Since the era of "thyroid cancer epidemic," many Korean academic societies discouraged the use of ultrasonography in healthy individuals and revised the Korean Thyroid Imaging Reporting and Data System to address the overscreening and overdiagnosis issues. This study aimed to evaluate the change in the diagnostic effectiveness of thyroid cancer screening over the last decade. METHODS: This single-center, retrospective observational study analyzed the data of 125,962 thyroid nodules obtained during cancer screening at the health promotion center of Seoul National University Bundang Hospital from 2010 to 2019. Only 327 thyroid cancer cases pathologically confirmed by fine-needle aspiration (FNA) were included in the study. The strength of the association between the number of FNA and (1) the number of thyroid cancer diagnoses, (2) the positive predictive values (PPVs), and (3) the difference in PPV from the previous year were evaluated using Pearson's correlation analysis. RESULTS: The number of thyroid FNA biopsies as well as the thyroid cancer diagnoses decreased from 2010 to 2019 (166 to 48 [-71.1%] vs. 43 to 22 [-48.8%]). The PPV of FNA biopsies increased from 25.9% to 45.8% (+76.8%) and was negatively correlated with the number of FNA biopsies performed (R=-0.87, P<0.001). The difference in PPV from the previous year increased similarly but without statistical significance (R=-0.59, P=0.09). CONCLUSION: The diagnostic efficiency of thyroid cancer screening has increased over the last decade, as evidenced by the increasing PPV of FNA biopsies.

8.
Am J Surg Pathol ; 46(10): 1397-1406, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35834399

RESUMO

Pediatric-type follicular lymphoma (PTFL) and pediatric nodal marginal zone lymphoma (PNMZL) are rare pediatric-type indolent B-cell lymphomas (PedIBCL) that differ clinicopathologically from their adult counterparts. Accurate diagnosis is important to avoid overtreatment but is often challenging. The mutational landscape of PTFL is known and may aid diagnosis, but the genetic features of PNMZL are not well understood. We analyzed 21 cases of PedIBCL according to their clinicopathologic findings and classified them into PTFL (n=11), PNMZL (n=2), and "mixed type" tumors (n=8) showing ambiguous histology. We also analyzed 2 cases of adult B-cell lymphomas showing features of PedIBCL. Targeted sequencing of 121 lymphoma-related genes was performed. The median age of PedIBCL patients was 16 years (range: 3 to 47), and all but 1 PTFL patient were male. All patients presented with limited-stage disease, and only 1 relapsed. There were no significant differences in clinical features among the 3 PedIBCL groups. The most frequently mutated genes were MAP2K1 , TNFRSF14 , KMT2C , IRF8 , and NOTCH2 . The genetic features of all groups were similar to the established mutational landscape of PTFL. The 2 adult B-cell lymphomas cases also had MAP2K1 , TNFRSF14 , and IRF8 mutations, but the clinical features were not typical of PedIBCL. In summary, this study demonstrated that PTFL and PNMZL are similar diseases with overlapping clinical, pathologic, and genetic features; mixed type tumors can also occur. Atypical adult cases with similar histologic features were also observed. Therefore, the disease spectrum of PedIBCL may be much broader than is currently believed.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Linfoma de Células B , Linfoma Folicular , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Fatores Reguladores de Interferon/metabolismo , Linfoma de Células B/diagnóstico , Linfoma de Células B/genética , Linfoma de Células B/terapia , Linfoma de Zona Marginal Tipo Células B/genética , Linfoma de Zona Marginal Tipo Células B/terapia , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Adulto Jovem
9.
Aesthetic Plast Surg ; 46(4): 2031-2039, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35237879

RESUMO

BACKGROUND: Examining the characteristics of the growing cosmetic surgery (CS) consumer population could help promote safer cosmetic procedure practices. We identified the predictors of acceptance of cosmetic surgery (ACS) among South Korean women aged 20-69 years. METHODS: An online survey was administered to 291 randomly sampled participants during August 30-September 6, 2021. An equal number of participants from each age group was selected. They completed a questionnaire concerning the general and CS-related characteristics, acceptance of cosmetic surgery scale, appearance satisfaction, self-esteem, and depression. The mean participants' age and body mass index were 44.12 (± 13.79) years and 22.15 (± 3.39) kg/m2, respectively. RESULTS: Approximately 90.0% of the participants had been exposed to a CS advertisement, with 96.2% having acquired information regarding the CS side effects and 52.6% considering CS in future. Eighty-eight (30.2%) participants had undergone CS. The most common surgical and non-surgical categories were eyelid surgery and botulinum toxin injection, respectively. The ACS increased with decreasing age (ß = - 0.12, p < .05), exposure to a CS advertisement (ß = 0.10, p < .05), consideration of undergoing CS in future (ß = 0.59, p < .001), and increasing depression scores (ß = 0.29, p < .001); collectively, these factors explained 43.0% of the variance (F = 25.21, p < .001). CONCLUSIONS: "Consideration of undergoing CS" was the strongest ACS predictor in the multiple regression analysis for the entire study population and according to CS history. Future studies should conduct an in-depth analysis based on the current CS trends, intention to undergo CS in future, and past CS experiences of South Korean women aged 20-69 years. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Toxinas Botulínicas , Procedimentos de Cirurgia Plástica , Cirurgia Plástica , Feminino , Humanos , República da Coreia , Autoimagem , Cirurgia Plástica/métodos
10.
Medicine (Baltimore) ; 101(3): e28641, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35060551

RESUMO

ABSTRACT: This study explores the perception of female college students in South Korea regarding cosmetic surgery and its side effects.Face-to-face interviews were conducted with 28 female college students over a period of 4 months, starting in October 2019. All participants were female college students who had not undergone cosmetic surgery. The collected data were analyzed qualitatively, using conventional content analysis.Four categories and 13 subcategories were extracted from 112 meaningful codes reflecting perceptions related to cosmetic surgery and its associated side effects. The 4 categories that emerged in the study were: "reaction to the side effects of cosmetic surgery", "reasons for cosmetic surgery", "prospects of the participant's own cosmetic surgery", and "prerequisites for decision-making regarding cosmetic surgery".The results of this study could be used as reference material by surgeons to ensure safer cosmetic surgeries. A sufficient consideration period and patient education prior to selective cosmetic surgery would minimize patient complaints and expand the base of safe cosmetic surgery.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde/etnologia , Procedimentos de Cirurgia Plástica , Estudantes/psicologia , Cirurgia Plástica , Adolescente , Feminino , Humanos , Percepção , Procedimentos de Cirurgia Plástica/psicologia , República da Coreia , Cirurgia Plástica/psicologia , Adulto Jovem
11.
Sci Rep ; 11(1): 11942, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34099764

RESUMO

We investigated the prognostic influences of BCL1 and BCL2 expression on disease-free survival in breast cancer patients. BCL1 and BCL2 expression statuses were assessed by immunohistochemistry using tissue microarrays from 393 breast cancer patients. The Kaplan-Meier estimator and log-rank test were used for survival analyses. The Cox proportional hazards model was used to calculate hazard ratio (HR) and the 95% confidence interval (CI) of survival analyses. BCL1 expression revealed no impact on survival. The high BCL2 group showed superior disease-free survival compared with the low BCL2 group (p = 0.002), especially regarding local recurrence-free survival (p = 0.045) and systemic recurrence-free survival (p = 0.002). BCL2 expression was a significant prognostic factor by univariable analysis (HR, 0.528; 95% CI, 0.353-0.790; p = 0.002) and by multivariable analysis (HR, 0.547; 95% CI, 0.362-0.826; p = 0.004). High BCL2 expression was associated with higher disease-free survival in the hormone receptor (HRc)-positive and human epidermal growth factor receptor 2 (HER2)-negative (HRc(+)/HER2(-)) subtype only (p = 0.002). The high BCL2 group was associated with positive estrogen receptor (ER), positive progesterone receptor (PR), low histologic grade, and age ≤ 50 years. BCL1 expression had no prognostic impact, but BCL2 expression was a significant independent prognostic factor. High BCL2 expression was associated with higher disease-free survival, especially regarding local recurrence and systemic recurrence. The prognostic effect of BCL2 expression was effective only in the HRc(+)/HER2(-) subtype. Favorable clinicopathologic features and a strong association with the ER/PR status could partly explain the superior prognosis of the high BCL2 group. BCL2 expression could be utilized to assess the prognosis of breast cancer patients in clinical settings.


Assuntos
Biomarcadores Tumorais/biossíntese , Neoplasias da Mama/metabolismo , Ciclina D1/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica/métodos , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Análise Serial de Tecidos/métodos
12.
Eur J Surg Oncol ; 47(6): 1316-1323, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33558123

RESUMO

INTRODUCTION: Breast cancer co-occurred with thyroid cancer might be associated with thyroid hormone receptor (TR) and estrogen receptor (ER), but few have been reported. We aimed to investigate the expression and prognostic significance of ERs and TRs in such settings. MATERIAL AND METHODS: Tissue microarrays were constructed from 75 patients with breast and thyroid cancer (BC + TC) who were retrospectively recruited between 1999 and 2012 and 147 with breast cancer only (BC controls). The ERα, ERß, TRα, and TRß expression levels were analyzed by immunohistochemistry. RESULTS: TRα expression was more frequently observed in the BC + TC group than the BC control group both in the normal (51.5% vs 23.3%, respectively, p = 0.009) and cancer tissues (21.6% vs 6.8%, respectively, p = 0.001). The BC + TC group showed greater ERα-positivity in the cancer tissues (79.7% vs 58.7%, respectively, p = 0.002) than the BC control group. The degree of ERα- and TRα-positivity was unchanged by radioactive treatment or serum thyroid stimulating hormone levels. In the BC + TC group, ERα-positivity was associated with earlier disease stage I/IIA (81.0% vs 50.0%; p = 0.031) and lower recurrence rates (8.5% vs 40.0%; p = 0.002). TRα-positivity alone was not associated with any recurrence-free survival-related differences, and ERα- and TRα-negativity were associated with significantly shorter recurrence-free survival (p < 0.001). CONCLUSION: Enhanced ERα and TRα expression in breast cancer is associated with thyroid cancer occurrence, and the observed association with prognosis suggests the possible role of ERs and TRs in the link between breast cancer and thyroid cancer.


Assuntos
Neoplasias da Mama/metabolismo , Receptor alfa de Estrogênio/metabolismo , Recidiva Local de Neoplasia/metabolismo , Neoplasias Primárias Múltiplas/metabolismo , Receptores alfa dos Hormônios Tireóideos/metabolismo , Neoplasias da Glândula Tireoide/patologia , Adulto , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Receptor beta de Estrogênio/metabolismo , Feminino , Humanos , Glândulas Mamárias Humanas/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Receptores beta dos Hormônios Tireóideos/metabolismo , Neoplasias da Glândula Tireoide/radioterapia , Tireotropina/sangue , Análise Serial de Tecidos
13.
Int J Mol Sci ; 22(2)2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33435173

RESUMO

A number of urinary bladder urothelial carcinoma (UB UC) mRNA-based classification systems have been reported. It also has been observed that treatment response and prognosis are different for each molecular subtype. In this study, cytokeratin (CK)5/6 and CK20 immunohistochemistry (IHC) were performed, and IHC-based subgroup classification was applied. UB UC was classified into CK5/6 single-positive (SP), CK20 SP, double-positive (DP) and double-negative (DN) subgroups, and transcriptional analysis was performed. The results of gene ontology (GO) terms and functional analysis using differentially expressed genes indicate that, CK5/6 SP and DP subgroups were enriched in cell migration, immune activation, interleukin 6-Janus kinase-signal transducer and activator of transcription 3 (IL6-JAK-STAT3) signaling pathway and tumor necrosis factor-α signaling via the nuclear factor-κB (NF-κB) signaling pathway signature gene. In addition, compared with the other subgroups, the DN subgroup showed inhibited cell movement, cell migration, and cell activation. Furthermore, in survival analysis, the CK5/6 SP subgroup was significantly associated with poor progression-free survival (p = 0.008). The results of our study indicate that the CK5/6 positive subgroup exhibited high gene expression signature related to aggressive behavior and exhibited worse clinical outcome.


Assuntos
Queratina-5/genética , Queratina-6/genética , Transdução de Sinais , Neoplasias da Bexiga Urinária/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Movimento Celular , Feminino , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Queratina-20/análise , Queratina-20/genética , Queratina-5/análise , Queratina-6/análise , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Neoplasias da Bexiga Urinária/classificação , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/fisiopatologia
14.
Cancer Immunol Immunother ; 70(7): 2035-2048, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33420630

RESUMO

BACKGROUND: To evaluate the characteristics of the tumor immune-microenvironment in brain metastases of non-small-cell lung cancer (NSCLC), we investigated the immunophenotype of primary NSCLC and its brain metastasis. METHODS: Expression profiling of 770 immune-related genes in 28 tissues from primary and brain metastases of NSCLC was performed using the NanoString nCounter PanCancer Immune Profiling Panel. The immune cell profiles were validated by immunohistochemistry of 42 matched samples. RESULTS: Based on unsupervised clustering and principal component analysis of the immune-related gene expression profile, tumors were primarily clustered according to the involved organ and further grouped according to the EGFR mutation status. Fifty-four genes were significantly differentially expressed between primary and brain metastatic tumors. Clustering using these genes showed that tumors harboring mutated EGFR tended to be grouped together in the brain. Pathway analysis revealed that various immune-related functions involving immune regulation, T cell activity, and chemokines were enriched in primary tumors compared to brain metastases. Diverse immune-related pathways were upregulated in brain metastases of EGFR-mutated compared to EGFR-wild-type adenocarcinoma, but not in primary tumors. The interferon-γ-related gene signature was significantly decreased in brain metastases. The anti-inflammatory markers TOLLIP and HLA-G were upregulated in brain metastases. The proportions of most immune cell subsets were decreased in brain metastases, but those of macrophages and CD56dim-NK-cells were increased, as was the ratios of CD163+M2- to iNOS+M1-macrophages and NCR1+NK-cells to CD3+T cells. CONCLUSIONS: Our findings illustrate the immune landscape of brain metastases from NSCLC and reveal potential therapeutic strategies targeting cellular and non-cellular components of the tumor immune-microenvironment.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Encefálicas/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Neoplasias Pulmonares/imunologia , Mutação , Microambiente Tumoral/imunologia , Adulto , Idoso , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
15.
Cell Mol Life Sci ; 78(6): 2821-2838, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33067654

RESUMO

Dramatic cellular reorganization in mitosis critically depends on the timely and temporal phosphorylation of a broad range of proteins, which is mediated by the activation of the mitotic kinases and repression of counteracting phosphatases. The mitosis-to-interphase transition, which is termed mitotic exit, involves the removal of mitotic phosphorylation by protein phosphatases. Although protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) drive this reversal in animal cells, the phosphatase network associated with ordered bulk dephosphorylation in mitotic exit is not fully understood. Here, we describe a new mitotic phosphatase relay in which Wip1/PPM1D phosphatase activity is essential for chromosomal passenger complex (CPC) translocation to the anaphase central spindle after release from the chromosome via PP1-mediated dephosphorylation of histone H3T3. Depletion of endogenous Wip1 and overexpression of the phosphatase-dead mutant disturbed CPC translocation to the central spindle, leading to failure of cytokinesis. While Wip1 was degraded in early mitosis, its levels recovered in anaphase and the protein functioned as a Cdk1-counteracting phosphatase at the anaphase central spindle and midbody. Mechanistically, Wip1 dephosphorylated Thr-59 in inner centromere protein (INCENP), which, subsequently bound to MKLP2 and recruited other components to the central spindle. Furthermore, Wip1 overexpression is associated with the overall survival rate of patients with breast cancer, suggesting that Wip1 not only functions as a weak oncogene in the DNA damage network but also as a tumor suppressor in mitotic exit. Altogether, our findings reveal that sequential dephosphorylation of mitotic phosphatases provides spatiotemporal regulation of mitotic exit to prevent tumor initiation and progression.


Assuntos
Cromossomos/metabolismo , Mitose , Proteína Fosfatase 2C/metabolismo , Fuso Acromático/metabolismo , Anáfase , Aurora Quinase B/metabolismo , Proteína Quinase CDC2/metabolismo , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proteínas Cromossômicas não Histona/metabolismo , Cromossomos/genética , Dano ao DNA , Humanos , Cinesinas/antagonistas & inibidores , Cinesinas/genética , Cinesinas/metabolismo , Fosforilação , Ligação Proteica , Proteína Fosfatase 1/antagonistas & inibidores , Proteína Fosfatase 1/genética , Proteína Fosfatase 1/metabolismo , Proteína Fosfatase 2/antagonistas & inibidores , Proteína Fosfatase 2/genética , Proteína Fosfatase 2/metabolismo , Proteína Fosfatase 2C/antagonistas & inibidores , Proteína Fosfatase 2C/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Survivina/metabolismo
16.
Front Oncol ; 10: 527385, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33365265

RESUMO

Urothelial carcinoma (UC) is the most common histologic type of urinary bladder cancer, and muscle-invasive UC shows aggressive behaviors. Programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) blockades have been approved as standard treatments for patients with advanced stage UC. A total of 166 muscle-invasive urinary bladder cancer (MIBC) patients, who underwent transurethral resection of the bladder or cystectomy from 2004 to 2010 were included. We evaluated PD-L1 expression by the SP142 and SP263 assays and classified the cases "positive" or "negative" according to the manufacturer's recommendations. We performed immunohistochemistry (IHC) for cytokeratin (CK) 5/6, CK14, GATA3, FOXA1, and CK20 and classified samples as Basal-Squamous-like (BASQ) or non-BASQ subtype. The overall concordance rate for PD-L1 expression is 91.6% (152/166) (kappa = 0.732). The SP142 assay showed 15.1% positivity; the SP263 assay showed 23.5%. The high positivity in the SP142 and SP263 assay was significantly correlated with positive CK5/6, CK14 expression, negative GATA3, FOXA1, and CK20 expression. Classification according to IHC expression resulted in 12.0% (20/166) of samples being classified as BASQ subtype and 88.0% (146/166) of samples being classified as non-BASQ subtype. High positivity in the SP142 and SP263 assay was significantly correlated with the BASQ subtype (p < 0.001, both). Our study is the first to analyze the association of immunohistochemically defined BASQ and non-BASQ subtypes with two PD-L1 assays in MIBC. In conclusion, we revealed that a high PD-L1 positive rate in all PD-L1 assays was significantly associated with the BASQ-subtype, and these results suggest that the BASQ classification may be important to apply the PD-1/PD-L1 blockades in MIBC.

17.
J Clin Med ; 9(12)2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33256003

RESUMO

Although American Thyroid Association guidelines offer a risk stratification scheme for thyroid cancer patients, there is a continuous need for more sophisticated biomarkers that can predict disease progression. In this study, we aim to evaluate the prognostic value of class III beta-tubulin (TUBB3) and uncover the relationship between TUBB3 and invasive potential in thyroid carcinoma. Immunohistochemistry (IHC) for TUBB3 and E-cadherin was performed on a total of 254 cases of thyroid cancer specimens. Tumor budding at the invasive margin was evaluated. In vitro functional studies were also performed; the protein and mRNA levels of TUBB3 were compared among the five cell types at baseline, with transwell invasion and after blocking of TUBB3 by shRNA. IHC revealed that the levels of TUBB3 were higher in conventional papillary carcinomas (cPTCs) and anaplastic thyroid carcinomas (ATCs). In univariate analysis, high tumor budding and TUBB3 expression were associated with inferior progression-free survival in cPTC. The results of a Western blot and RT-PCR agreed with the IHC finding. The results were further validated through data from The Cancer Genome Atlas database. Our results suggest that high expression of TUBB3 in thyroid carcinoma could predict invasive potential and possibly be linked with epithelial-mesenchymal transition.

18.
Pediatr Surg Int ; 36(9): 1061-1066, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32676828

RESUMO

PURPOSE: The aim of this study was to identify the factors affecting the prognosis of children with foreign body aspiration (FBA) after undergoing rigid bronchoscopy. METHODS: This was a case series with a chart review of 49 children under 3 years of age who underwent rigid bronchoscopy for suspected FBA at a single tertiary institution. RESULTS: The time from symptom onset to hospitalization positively correlated with the total hospitalization time (p < 0.001), postoperative hospitalization time (p = 0.006), and operation time (p = 0.013). The time from symptom onset to operation positively correlated with the total hospitalization time (p < 0.001) and operation time (p = 0.046). The time from hospitalization to operation and the operation time positively correlated with the total hospitalization time (p = 0.026, 0.044) and postoperative hospitalization time (p = 0.049, 0.003). The time from symptom onset to hospitalization positively correlated with the incidence of pneumonia (p = 0.028). CONCLUSION: Rapid hospitalization after symptom onset, rapid surgery after symptom onset, and rapid surgery after hospitalization improve the prognosis of patients with FBA. Further, a short operation time also plays a role in improving patient prognosis.


Assuntos
Broncoscopia/métodos , Corpos Estranhos/cirurgia , Feminino , Corpos Estranhos/diagnóstico , Hospitalização/tendências , Humanos , Lactente , Recém-Nascido , Inalação , Masculino , Duração da Cirurgia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
19.
Aesthetic Plast Surg ; 44(5): 1881-1888, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32424531

RESUMO

BACKGROUND: This descriptive study investigates cosmetic surgery experience, awareness of side effects, self-esteem, and acceptance of cosmetic surgery (ACS) and aims to identify factors that affect ACS. METHODS: Data on 398 randomly selected participants from a panel of sex-stratified adults in their 20s and 30s registered online with a Korean survey company were collected in September 2019. The data were analyzed using descriptive statistics, crosstabs, Chi-square test, ANOVA, Pearson's correlation, and multiple linear regression. RESULTS: Among the subjects, 47.2% were male and 52.8% were female. The average age of the subjects was 29.98 years. While 91.7% of the subjects previously acquired information on side effects related to cosmetic surgery, the most frequent source was from "bus stops and subway stops," reported by 83.6% of them. Blepharoplasty was the most frequently performed procedure reported by 50 of the 89 subjects (22.4%) who underwent 1 or more cosmetic surgery procedures. Among 187 subjects (47.0%) considering cosmetic surgery in the future, "botulinum toxin" was the most frequently considered procedure. ACS of the subjects was higher with employment (ß = .15, p < .001), previous experience with cosmetic surgery (ß = .22, p < .001), consideration for future cosmetic surgery (ß = .49, p < .001), and lower appearance satisfaction (AS) (ß = -.10, p = .008), and the explanatory power of these variables was 41.7% (F = 72.08, p < .001). CONCLUSIONS: Most of the subjects in this study were aware of the side effects of cosmetic surgery, and about half were considering cosmetic surgery in the future. Employment status, previous experience with cosmetic surgery, consideration for future cosmetic surgery, and AS were found to be factors affecting ACS. Correlations between age, BMI, ACS, AS, depression, and self-esteem were identified. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the table of contents or the online instructions to authors www.springer.com/00266 .


Assuntos
Cirurgia Plástica , Adulto , Feminino , Humanos , Masculino , Satisfação Pessoal , Autoimagem , Inquéritos e Questionários
20.
Eur J Cancer ; 133: 74-85, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32447027

RESUMO

PURPOSE: B7-H3 has emerged as a promising target for cancer immunotherapy. We assessed the role of B7-H3 expression in tumour-infiltrating immune cells in non-small-cell lung cancer (NSCLC). METHODS: Tumour-infiltrating immune cell characterisation was performed by flow cytometry in a prospective cohort, whereas the relationship between B7-H3 expression and clinicopathological features was explored in a retrospective cohort. RESULTS: B7-H3 expression was detected in tumour/epithelial cells and immune cells, including macrophages, monocytes, dendritic cells (DCs) and myeloid-derived suppressor cells. B7-H3 was expressed at higher levels in cells within the tumour than in cells within non-neoplastic tissues. B7-H3 expression score in tumour cells positively correlated with the amount of CD45+ immune cells (rho = 0.305, P = 0.010), CD8+ T-cells (rho = 0.330, P = 0.005), and the percentage of CD8+/CD3+ T-cells (rho = 0.403, P < 0.001). Patients with high tumoural B7-H3 expression showed increased numbers of immune cells (P = 0.002), CD8+ T-cells (P = 0.011), natural killer cells (P = 0.073) and plasmacytoid DCs (P = 0.015). Tumoural B7-H3 expression was higher in males, smokers, squamous cell carcinomas, tumours with wild-type EGFR, poor differentiation, larger size and nodal metastasis (P < 0.05, all). Tumoural B7-H3 expression was associated with PD-L1 expression (P = 0.001), shorter 5-year overall survival (P = 0.012) and poor survival after anti-PD-1 blockade (P = 0.026). CONCLUSIONS: Tumoural B7-H3 overexpression was associated with increased tumour-infiltrating cytotoxic lymphocytes and poor prognosis in NSCLC. Thus, B7-H3 is a promising prognostic biomarker and immunotherapeutic target in NSCLC.


Assuntos
Antígenos B7/metabolismo , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Linfócitos do Interstício Tumoral/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Contagem de Linfócitos , Linfócitos do Interstício Tumoral/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
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