RESUMO
Background: Poorly differentiated thyroid carcinoma (PDTC) accounts for a small portion of thyroid carcinomas but contributes to a significant proportion of thyroid carcinoma-associated deaths. The clinicopathological prognostic factors and clinical outcomes of PDTC remain unclear. We aimed to evaluate the clinical outcomes of patients with PDTC after curative treatment. Methods: A comprehensive search was performed up to September 2023. We included studies investigating treatment outcomes in patients with PDTC who underwent initial surgery. The 5-year disease-free survival (DFS) and overall survival (OS) were extracted. In this meta-analysis, the enrolled PDTC histological criteria included 3rd, 4th, and 5th World Health Organization (WHO) and Memorial Sloan Kettering Cancer Center (MSKCC) classification. A random-effects model was used for the pooled proportion analysis. Meta-regression analysis was conducted to evaluate the prognostic factors. Results: Twenty retrospective studies published between 2007 and 2023, including 1,294 patients, met all inclusion criteria. Studies that diagnosed PDTC based on various histological criteria including 3rd WHO (n=5), 4th WHO (n=12), 5th WHO (n=2), and MSKCC (n=1) were included. Overall, 5-year DFS and 5-year OS were 49.4% (95% confidence interval [CI], 42.3 to 56.4) and 73.8% (95% CI, 66.5 to 79.9), with moderate heterogeneity of 58% and 55%, respectively. In meta-regression analysis, extrathyroidal extension (ETE) was a prognostic factor for OS. Conclusion: The meta-analysis of DFS and OS in patients with PDTC show the moderate heterogeneity with a variety of histological criteria. ETE appears to have a significant impact on OS, regardless of histological criteria.
RESUMO
BACKGROUND: This study was conducted to evaluate the feasibility and surgical outcomes of minimally invasive video-assisted thyroidectomy (MIVAT) and three remote-access approaches, namely the robotic bilateral axillo-breast approach (BABA-R), endoscopic breast-chest approach (BCA-E), and robotic gasless transaxillary approach (GTAA-R) in lateral neck dissection for papillary thyroid carcinoma, compared with conventional transcervical approach (CTA). METHODS: The literature search was conducted in the PubMed, EMBASE, and Cochrane Library databases, covering the period January 2000 to February 2024. A systematic review and network meta-analysis were performed to compare surgical feasibility, safety, and oncologic outcomes between approaches. RESULTS: Fourteen articles on lateral neck dissection in patients with papillary thyroid carcinoma were included after systematic screening. The number of removed and metastatic lateral lymph nodes, the extent of lateral neck dissection, the rate of transient recurrent laryngeal nerve palsy and hypoparathyroidism, serum-stimulated thyroglobulin levels, and recurrence were not significantly different between the MIVAT and three remote-access approaches. Additionally, these were comparable to those of the CTA. However, the MIVAT and remote-access approaches took a longer operative time but provided superior cosmetic outcomes compared to the CTA. CONCLUSION: Lateral neck dissection using the MIVAT and three remote-access approaches was feasible and comparable to CTA in the number of lymph nodes removed, complications, stimulated thyroglobulin level, and recurrence. The MIVAT and remote-access approaches lasted longer but provided significantly superior cosmetic outcomes compared to the CTA.
RESUMO
BACKGROUND: Despite the therapeutic success of trastuzumab, HER2 positive (HER2+) breast cancer patients continue to face significant difficulties due to innate or acquired drug resistance. In this study we explored the potential role of CTTN in inducing trastuzumab resistance of HER2+ breast cancers. METHODS: Genetic changes of CTTN and survival of HER2+ breast cancer patients were analyzed in multiple breast cancer patient cohorts (METABRIC, TCGA, Kaplan-Meier (KM) plotter, and Hanyang University cohort). The effect of CTTN on cancer stem cell activity was assessed using the tumorsphere formation, ALDEFLUOR assay, and by in vivo xenograft experiments. CTTN-induced trastuzumab resistance was assessed by the sulforhodamine B (SRB) assay, colony formation assays, and in vivo xenograft model. RNA-seq analysis was used to clarify the mechanism of trastuzumab resistance conferred by CTTN. RESULTS: Survival analysis indicated that CTTN overexpression is related to a poor prognosis in HER2+ breast cancers (OS, p = 0.05 in the Hanyang University cohort; OS, p = 0.0014 in KM plotter; OS, p = 0.008 and DFS, p = 0.010 in METABRIC). CTTN overexpression-induced cancer stem cell-like characteristics in experiments of tumorsphere formation, ALDEFLUOR assays, and in vivo limiting dilution assays. CTTN overexpression resulted in trastuzumab resistance in SRB, colony formation assays, and in vivo xenograft models. Mechanistically, the mRNA and protein levels of DKK-1, a Wnt antagonist, were downregulated by CTTN. Treatment of the ß-catenin/TCF inhibitor reversed CTTN-induced cancer stem cell-like properties in vitro. Combination treatment with trastuzumab and ß-catenin/TCF inhibitor overcame trastuzumab resistance conferred by CTTN overexpression in in vitro colony formation assays. CONCLUSIONS: CTTN activates DKK-1/Wnt/ß-catenin signaling to induce trastuzumab resistance. We propose that CTTN is a novel biomarker indicating a poor prognosis and a possible therapeutic target for overcoming trastuzumab resistance.
RESUMO
Papillary thyroid cancer (PTC) is the most prevalent histological type of thyroid cancer (TC) worldwide. Although tumor metastasis occurs in regional lymph nodes, distant metastasis (DM) may also occur. Radioactive iodine (RAI) therapy is an effective treatment for TC; however, resistance to RAI occurs in patients with DM. Therefore, in this study, we investigated the efficacy of DM-related biomarkers as therapeutic targets for PTC therapy. ABCA1 expression was higher in aggressive BCPAP cells than in other PTC cells in terms of migration and invasion capacity. The knockdown of ABCA1 substantially decreased the expression of the epithelial-mesenchymal transition (EMT) marker, N-cadherin, and EMT regulator (ZEB1), resulting in suppressed migration and invasion of BCPAP cells. ABCA1 knockdown also reduced ERK activity and Fra-1 expression, which correlated with the effects of an ERK inhibitor or siRNA-mediated inhibition of ERK or Fra-1 expression. Furthermore, ABCA1-knocked-down BCPAP cells suppressed cell migration and invasion by reducing Fra-1 recruitment to Zeb1 promoter; lung metastasis was not observed in mice injected with ABCA1-knocked-down cells. Overall, our findings suggest that ABCA1 regulates lung metastasis in TC cells.
Assuntos
Neoplasias Pulmonares , Neoplasias da Glândula Tireoide , Animais , Camundongos , Transportador 1 de Cassete de Ligação de ATP , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Radioisótopos do Iodo , Invasividade Neoplásica , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismoRESUMO
BACKGROUND: This study aimed to evaluate the incidence and risk factors of occult metastasis to superficial level VI, defined as the space anterior to the strap muscles, including the lymph nodes between the sternocleidomastoid and sternohyoid muscles and suprasternal space lymph nodes. METHODS: We studied 129 patients with papillary thyroid carcinoma who underwent thyroidectomy and neck dissection, including superficial level VI dissection. RESULTS: Of the 129 patients, 62 (48%) had lymph nodes in the harvested specimens of superficial level VI, and the mean number of lymph nodes retrieved was 1.9 ± 1.2. Occult metastasis to superficial level VI occurred in four patients (3.1%). No significant risk factors of superficial level VI occult metastasis were noted in multivariate analysis. CONCLUSIONS: Occult metastasis to superficial level VI was rare in patients with papillary thyroid carcinoma. Therefore, prophylactic dissection of superficial level VI may not be necessary for primary papillary thyroid carcinoma.
Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/patologia , Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Metástase Linfática/patologia , Esvaziamento Cervical , Linfonodos/patologia , Tireoidectomia , Estudos RetrospectivosRESUMO
Lgr5 has been identified as a marker of the stem/progenitor cells in the murine ovary and oviduct by lineage tracing. However, little is known regarding LGR5 expression or its functional significance in human ovary tissues. Here, using RNA in situ hybridization and/or immunohistochemistry, we thoroughly investigated LGR5 expression in normal human ovaries, fallopian tubes and various ovarian tumors. We discovered that LGR5 expression is negligible in the human ovary surface epithelium, whereas ovarian stromal cells normally express low levels of LGR5. Remarkably, fallopian tube epithelium, inclusion cysts and serous cystadenomas with a Müllerian phenotype expressed high levels of LGR5, and LGR5 expression was restricted to PAX8+/FOXJ1- secretory cells of the tubal epithelium. Strong stromal LGR5 expression without epithelial LGR5 expression was consistently observed in the path from serous cystadenoma to serous borderline tumor to low grade serous carcinoma (LGSC). Unlike LGSC, high grade serous carcinoma (HGSC), clear cell carcinoma, endometrioid carcinomas displayed various epithelial-stromal LGR5 expression. Notably, high levels of LGR5 expression were observed in serous tubal intraepithelial carcinoma, which slightly declined in invasive HGSC. LGR5 expression was significantly associated with improved progression-free survival in HGSC patients. Moreover, in vitro assays demonstrated that LGR5 expression suppressed tumor proliferation and migratory capabilities. Taken together, these findings indicate a tumor-suppressive role for LGR5 in the progression of HGSC.
Assuntos
Cistadenocarcinoma Seroso , Neoplasias das Tubas Uterinas , Animais , Carcinogênese/patologia , Cistadenocarcinoma Seroso/patologia , Neoplasias das Tubas Uterinas/patologia , Tubas Uterinas/metabolismo , Feminino , Humanos , Camundongos , Ovário/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismoRESUMO
BACKGROUND: Glioblastoma multiforme (GBM) is an aggressive malignant primary brain tumor. Wnt/ß-catenin is known to be related to GBM stemness. Cancer stem cells induce immunosuppressive and treatment resistance in GBM. We hypothesized that Wnt/ß-catenin-related genes with immunosuppression could be related to the prognosis in patients with GBM. METHODS: We obtained the clinicopathological data of 525 patients with GBM from the brain cancer gene database. The fraction of tumor-infiltrating immune cells was evaluated using in silico flow cytometry. Among gene sets of Wnt/ß-catenin pathway, Dickkopf-3 (DKK3) gene related to the immunosuppressive response was found using machine learning. We performed gene set enrichment analysis (GSEA), network-based analysis, survival analysis and in vitro drug screening assays based on Dickkopf-3 (DKK3) expression. RESULTS: In analyses of 31 genes related to Wnt/ß-catenin signaling, high DKK3 expression was negatively correlated with increased antitumoral immunity, especially CD8 + and CD4 + T cells, in patients with GBM. High DKK3 expression was correlated with poor survival and disease progression in patients with GBM. In pathway-based network analysis, DKK3 was directly linked to the THY1 gene, a tumor suppressor gene. Through in vitro drug screening, we identified navitoclax as an agent with potent activity against GBM cell lines with high DKK3 expression. CONCLUSIONS: These results suggest that high DKK3 expression could be a therapeutic target in GBM. The results of the present study could contribute to the design of future experimental research and drug development programs for GBM.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/patologia , beta Catenina/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neoplasias Encefálicas/patologia , Prognóstico , Terapia de Imunossupressão , Aprendizado de Máquina , Linhagem Celular Tumoral , Proliferação de Células , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismoRESUMO
The protein tyrosine kinase Ephrin type-B receptor 2 (EPHB2) belongs to one of the intestinal stem cell signature genes and plays a crucial role in maintaining the crypt-villous axis. Herein, we aimed to investigate the expression of EPHB2 during gastric carcinogenesis and evaluated its prognostic and functional significance in gastric cancer (GC). EPHB2 expression was upregulated in intestinal metaplasia and GCs compared to normal antral and fundic glands. EPHB2 mRNA levels were strongly correlated with the intestinal stem cell markers OLFM4, LGR5, and EPHB3. Notably, EPHB2 expression was significantly correlated with CDX2 expression, and in vitro studies demonstrated that CDX2 expression increased both EPHB2 transcription and protein levels. In a large cohort of GC patients, EPHB2 positivity was observed in 39% of 704 GCs and was negatively correlated with tumor differentiation, lymphovascular invasion, and tumor-node-metastasis stages. Notably, EPHB2 positivity was associated with better overall survival, and it was an independent prognostic marker in intestinal-type GCs. Overexpression of EPHB2 in GC cell lines, MKN-28 and MKN-74, reduced migration activity by suppressing phosphorylation of focal adhesion kinase, whereas no significant difference was observed in proliferation rates. Thus, we suggest that EPHB2 acts as a tumor suppressor in GCs and can be a prognostic marker in intestinal-type GCs.
RESUMO
The histogenesis of pleomorphic adenoma (PA) of the salivary glands remains controversial. PAs are characterized by the transition of epithelial cells to spindled mesenchymal cells, known as epithelial-mesenchymal transition (EMT). The present study aimed to identify a major EMT-inducing transcription factor (EMT-TF) in PAs. Real-time PCR analysis of SNAIL, SLUG, ZEB1, and TWIST1 demonstrated that only SLUG was significantly upregulated in normal salivary glands and PAs. Combined in situ hybridization for SLUG and multiplex immunohistochemistry for CK19 and P63 revealed that SLUG was specifically expressed in the myoepithelial cells of normal salivary glands. In PAs, SLUG was expressed in neoplastic myoepithelial cells and stromal cells but not in the luminal cells lining the inner layers of tumor glands. SLUG expression showed no correlation with PLAG1 expression, and in vitro experiments demonstrated that PLAG1 suppression in primary cultured PA cells or PLAG1 overexpression in HEK 293 T cells did not affect SLUG levels, indicating that PLAG1 was not involved in the upregulation of SLUG in PAs. The suppression of SLUG expression in cultured PA cells resulted in a morphology change to a less elongated shape and attenuated tumor growth. In addition, SLUG downregulation led to increased E-cadherin and decreased N-cadherin and vimentin expression levels along with decreased migratory activity in cultured PA cells. These findings suggest that SLUG is a major TF that can induce EMT in PAs. In summary, SLUG is specifically and highly expressed in the myoepithelial cells and stromal cells of PAs and is a key regulator of EMT in PAs.
Assuntos
Adenoma Pleomorfo , Fatores de Transcrição da Família Snail , Adenoma Pleomorfo/química , Adenoma Pleomorfo/genética , Adenoma Pleomorfo/metabolismo , Transição Epitelial-Mesenquimal , Células HEK293 , Humanos , Imuno-Histoquímica , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/metabolismoRESUMO
Androgen exerts its functions by binding with an androgen receptor (AR). It can activate many signaling pathways that are important to the progression of castration-resistant prostate cancer (CRPC). Here, we characterized the rapid proteomic changes seen at 5, 15, 30, and 60 min after the androgen treatment of VCaP cells via the tandem mass tag (TMT) labeling strategy. A total of 5529 proteins were successfully identified and quantified. Dynamic time profiling of protein expression patterns allowed us to identify five protein clusters involved in various stages of androgen-initiated signal transmission and processing. More details of protein functions and localization patterns, and our elucidation of an AR-interacting protein network, were obtained. Finally, we validated the expression level of AR-regulated proteins known to be significantly regulated in CRPC patients using the mouse xenograft model and patient samples. Our work offers a systematic analysis of the rapid proteomic changes induced by androgen and provides a global view of the molecular mechanisms underlying CRPC progression.
RESUMO
Although thyroid cancer is the most prevalent endocrine malignancy, overall patients with thyroid cancer have a good long-term survival. However, a small percentage of patients with progressive thyroid cancer have poor outcomes, and the genetic drivers playing a key role thyroid cancer progression are mostly unknown. Here, we investigated the role of the PINX1 in thyroid cancer progression. Interestingly, PINX1 expression was significantly higher in ATC than in PTC in both patients and cell lines. When PINX1 was knockdown in ATC cells, cell proliferation rates, colony formation capacity, and cell cycle progression were significantly reduced. Furthermore, cell motility and the expression of EMT drivers were reduced by PINX1 downregulation. In contrast, the overexpression of PINX1 in PTC cells significantly increased those phenotypes of tumor progression, which demonstrates that PINX1 could promote tumor proliferation and malignant transformation in both PTC and ATC cells. To further understand whether PINX1 is also involved in the progression of PTC to ATC, we examined PI3K/AKT, MAPK, and ß-catenin signaling activation after PINX1 modulation. Decreased PINX1 expression reduced the levels of p-AKT, p-ERK, p-p38, and ß-catenin in ATC cells, but the increase of PINX1 expression upregulated the phosphorylation of AKT, ERK, and p38 and the levels of ß-catenin in PTC cells. These results were all confirmed in xenograft mouse tumors. Our findings suggest that PINX1 regulates thyroid cancer progression by promoting cell proliferation, EMT, and signaling activation, and support the hypothesis that PINX1 could be a prognostic marker and a therapeutic target of thyroid cancer.
RESUMO
Triple-negative breast cancers (TNBCs) are characterized by high rates of recurrence and poor clinical outcomes. Deregulated E3 ligases are involved in breast cancer pathogenesis and progression, but the underlying mechanisms are unclear. Here, we find that F-box and leucine-rich repeat protein 16 (FBXL16) acts as a tumor suppressor in TNBCs. FBXL16 directly binds to HIF1α and induces its ubiquitination and degradation, regardless of the tumor microenvironment, resulting in blockade of the HIF1α-mediated epithelial-mesenchymal transition (EMT) and angiogenesis features of breast cancer. In TNBCs, FBXL16 expression is downregulated by the p38/miR-135b-3p axis, and loss of FBXL16 expression restores HIF1α-mediated metastatic features of breast cancer. Low expression of FBXL16 is associated with high-grade and lymph node-positive tumors and poor overall survival of breast cancer. Taken together, these findings demonstrate that modulation of FBXL16 expression may offer a favorable strategy for treatment of patients with metastatic breast cancer, including TNBCs.
Assuntos
Neoplasias da Mama/genética , Proteínas F-Box/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Animais , Biomarcadores Tumorais , Mama , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Proteínas F-Box/metabolismo , Feminino , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Genes Supressores de Tumor/fisiologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Proteínas de Repetições Ricas em Leucina/metabolismo , Camundongos , Camundongos Endogâmicos NOD , MicroRNAs/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Microambiente Tumoral/genéticaRESUMO
Androgen signaling via the androgen receptor (AR) is involved in normal prostate development and prostate cancer progression. In addition to androgen binding, a variety of protein kinases, including cyclic AMP-dependent protein kinase A (PKA), can activate the AR. Although hormone deprivation, especially that of androgen, continues to be an important strategy for treating prostate cancer patients, the disease ultimately progresses to castration-resistant prostate cancer (CRPC), despite a continuous hormone-deprived environment. To date, it remains unclear which pathways in this progression are active and targetable. Here, we performed a proteomic analysis of VCaP cells stimulated with androgen or forskolin to identify proteins specific for androgen-induced and androgen-bypassing signaling, respectively. Patterns of differentially expressed proteins were quantified, and eight proteins showing significant changes in expression were identified. Functional information, including a Gene Ontology analysis, revealed that most of these proteins are involved in metabolic processes and are associated with cancer. The mRNA and protein expression of selected proteins was validated, and functional correlations of identified proteins with signaling in VCaP cells were assessed by measuring metabolites related to each enzyme. These analyses offered new clues regarding effector molecules involved in prostate cancer development, insights that are supported by the demonstration of increased expression levels of the eight identified proteins in prostate cancer patients and assessments of the progression-free interval. Taken together, our findings show that aberrant levels of eight proteins reflect molecular changes that are significantly regulated by androgen and/or PKA signaling pathways, suggesting possible molecular mechanisms of CRPC.
RESUMO
Lineage tracing in mice indicates that LGR5 is an adult stem cell marker in multiple organs, such as the intestine, stomach, hair follicles, ovary, and mammary glands. Despite many studies exploring the presence of LGR5 cells in human tissues, little is known about its expression profile in either human mammary tissue or pathological lesions. In this study we aim to investigate LGR5 expression in normal, benign, and malignant lesions of the human breast using RNA in situ hybridization. LGR5 expression has not been observed in normal lactiferous ducts and terminal duct lobular units, whereas LGR5-positive cells have been specifically observed in the basal myoepithelium of ducts in the regenerative tissues, ductal carcinoma in situ, and in ducts surrounded by invasive cancer cells. These findings suggest LGR5 marks facultative stem cells that are involved in post injury regeneration instead of homeostatic stem cells. LGR5 positivity was found in 3% (9 of 278 cases) of invasive breast cancers (BC), and it showed positive associations with higher histologic grades (P = 0.001) and T stages (P < 0.001), while having negative correlations with estrogen receptor (P < 0.001) and progesterone receptor (P < 0.001) expression. Remarkably, all LGR5-positive BC, except one, belong to triple-negative BC (TNBC), representing 24% (9 of 38 cases) of all of them. LGR5 histoscores have no correlations with EGFR, CK5/6, Ki-67, or P53 expression. Additionally, no ß-catenin nuclear localization was observed in LGR5-positive BC, indicating that canonical Wnt pathway activation is less likely involved in LGR5 expression in BC. Our results demonstrate that LGR5 expression is induced in regenerative conditions in the myoepithelium of human mammary ducts and that its expression is only observed in TNBC subtype among all invasive BC. Further studies regarding the functional and prognostic impact of LGR5 in TNBC are warranted.
Assuntos
Mama/metabolismo , Células Epiteliais/metabolismo , Proteínas de Neoplasias/biossíntese , Receptores Acoplados a Proteínas G/biossíntese , Neoplasias de Mama Triplo Negativas/metabolismo , Adulto , Idoso , Mama/citologia , Mama/fisiologia , Doenças Mamárias/genética , Doenças Mamárias/metabolismo , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/metabolismo , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/metabolismo , Feminino , Fibroadenoma/genética , Fibroadenoma/metabolismo , Humanos , Hibridização In Situ , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Papiloma Intraductal/genética , Papiloma Intraductal/metabolismo , Tumor Filoide/genética , Tumor Filoide/metabolismo , RNA Mensageiro/biossíntese , RNA Neoplásico/biossíntese , Receptores Acoplados a Proteínas G/genética , Regeneração/genética , Neoplasias de Mama Triplo Negativas/genéticaRESUMO
BACKGROUND/AIM: Dual-specificity protein phosphatase 4 (DUSP4) negatively regulates MAPK signaling and is involved in various cellular processes. We herein evaluated the relationship between DUSP4 expression and clinicopathological characteristics in a large series of gastric cancer samples. MATERIALS AND METHODS: DUSP4 expression was examined by immunohistochemistry in 508 gastric cancer samples. Cases were classified according to the TCGA molecular classification and HER2 amplification. Kaplan-Meier plots were used to predict the relationship between mRNA expression of DUSP4 and survival. RESULTS: Low expression of DUSP4 was significantly correlated with larger tumor size, higher pT category, positive nodal status, higher stage, lymphovascular invasion, perineural invasion, worse overall survival, and worse recurrence-free survival. No correlation was observed between DUSP4 expression and molecular characteristics. Bioinformatics analysis showed that low mRNA expression was associated with a poor prognosis. CONCLUSION: Low expression of DUSP4 is associated with aggressive phenotypes of gastric cancer and a poor prognosis.
Assuntos
Neoplasias Gástricas , Fosfatases de Especificidade Dupla/genética , Humanos , Imuno-Histoquímica , Fosfatases da Proteína Quinase Ativada por Mitógeno/genética , Fenótipo , Prognóstico , Neoplasias Gástricas/genéticaRESUMO
BACKGROUND/AIM: Both pediatric glioblastoma (pGB) and adult glioblastoma (aGB) are clinically devastating, and are known to have different molecular pathogenesis. Here, we focused on the role of ZEB2 in pGB and aGB. MATERIALS AND METHODS: Following transfection with ZEB2 siRNA into pGB cells (KNS42) and aGB cells (U87 and U373), cell proliferation, migration and invasion, and cell cycle progression were evaluated. RESULTS: Targeted inhibition of ZEB2 induced up-regulation of E-cadherin expression and down-regulation of vimentin expression. Furthermore, it reduced invasion and migration of both pGB and aGB cells. Interestingly, in pGB cells, but not in aGB cells, silencing of ZEB2 reduced cell proliferation and viability, and affected the cell cycle progression of tumor cells. CONCLUSION: Inhibition of ZEB2 altered the mesenchymal features and reduced the migration and invasive ability of both pGB and aGB cells. ZEB2 effects were different in pGB and aGB cells regarding proliferation and cell cycle progression, suggesting that different underlying molecular mechanisms drive progression in these two types of tumors.
Assuntos
Expressão Gênica , Glioblastoma/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , Adulto , Fatores Etários , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Criança , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Glioblastoma/metabolismo , Humanos , Imuno-Histoquímica , Imunofenotipagem , MicroRNAs/genética , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismoRESUMO
INTRODUCTION: This study aimed to investigate the positive rate of human papillomavirus (HPV) and its trend in head and neck squamous cell carcinoma (HNSCC) in South Korea and to evaluate the clinical differences between HPV-positive and -negative tumors. METHODS: We studied 300 patients with HNSCC arising in the oropharynx (n = 77), oral cavity (n = 65), larynx (n = 106), hypopharynx (n = 40), and sinonasal cavity (n = 12), treated in a tertiary university hospital in South Korea from January 2008 to July 2020. HPV status was determined using p16 immunohistochemical staining of formalin-fixed paraffin-embedded tissues. RESULTS: Of the 300 patients with HNSCC, the positive rate of p16 was 30.3% (91/300). The p16 positive rate was 70.1, 13.9, 20.8, 15, and 0% in the oropharynx, oral cavity, larynx, hypopharynx, and sinonasal cavity, respectively. HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) patients were significantly younger than HPV-negative OPSCC patients. The positive rate of HPV in OPSCC has increased over time from 2008 to 2020, but has not changed significantly in the other primary sites. The disease-free survival curve of HPV-positive OPSCC was significantly better than that of HPV-negative tumors. CONCLUSION: The positive rate of HPV in Korean patients with OPSCC is significantly high (70.1%), similar to that in North America and Europe, and has increased abruptly in the past 12 years.
RESUMO
OBJECTIVES/HYPOTHESIS: Ultrasound-guided fine-needle aspiration cytology (US-FNAC) is a well-established procedure performed to establish the diagnosis of Kikuchi-Fujimoto disease (KFD). Ultrasound-guided core needle biopsy (US-CNB) is an alternative diagnostic tool for KFD. However, the efficacy of US-CNB is not well evaluated. This study aimed to evaluate the efficacy of US-CNB and compare it with that of US-FNAC in the diagnosis of KFD. STUDY DESIGN: Retrospective cohort study. METHODS: We analyzed 170 patients who were diagnosed with KFD between January 2009 and May 2019. US-FNAC, US-CNB, and excisional biopsy were performed in 47, 114, and 9 patients, respectively. Diagnostic accuracies of US-FNAC and US-CNB were analyzed and compared. RESULTS: Of the 170 patients, 45 and 125 were men and women, respectively. The mean age was 26.9 ± 9.1 years. The most common symptom was cervical lymphadenopathy, followed by fever, headache, and myalgia. The diagnosis of KFD was established primarily by US-FNAC in 21 (44.7%) of the 47 patients, by US-CNB in 109 (95.6%) of the 114 patients, and by excisional biopsy in all 9 patients. There was no specific major complication related to US-FNAC and US-CNB. CONCLUSION: US-CNB can be considered safe and effective and used as the primary modality for the pathological diagnosis of KFD. LEVEL OF EVIDENCE: 4. Laryngoscope, 131:E1519-E1523, 2021.
Assuntos
Linfadenite Histiocítica Necrosante/diagnóstico , Linfonodos/patologia , Adolescente , Adulto , Axila , Biópsia com Agulha de Grande Calibre/efeitos adversos , Biópsia com Agulha de Grande Calibre/métodos , Biópsia com Agulha de Grande Calibre/estatística & dados numéricos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/efeitos adversos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/estatística & dados numéricos , Feminino , Virilha , Linfadenite Histiocítica Necrosante/patologia , Humanos , Masculino , Pescoço , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto JovemRESUMO
PURPOSE: Gastric cancer remains the leading cause of cancer-related deaths in Northeast Asia. Population-based endoscopic screenings in the region have yielded successful results in early detection of gastric tumors. Endoscopic screening rates are continuously increasing, and there is a need for an automatic computerized diagnostic system to reduce the diagnostic burden. In this study, we developed an algorithm to classify gastric epithelial tumors automatically and assessed its performance in a large series of gastric biopsies and its benefits as an assistance tool. EXPERIMENTAL DESIGN: Using 2,434 whole-slide images, we developed an algorithm based on convolutional neural networks to classify a gastric biopsy image into one of three categories: negative for dysplasia (NFD), tubular adenoma, or carcinoma. The performance of the algorithm was evaluated by using 7,440 biopsy specimens collected prospectively. The impact of algorithm-assisted diagnosis was assessed by six pathologists using 150 gastric biopsy cases. RESULTS: Diagnostic performance evaluated by the AUROC curve in the prospective study was 0.9790 for two-tier classification: negative (NFD) versus positive (all cases except NFD). When limited to epithelial tumors, the sensitivity and specificity were 1.000 and 0.9749. Algorithm-assisted digital image viewer (DV) resulted in 47% reduction in review time per image compared with DV only and 58% decrease to microscopy. CONCLUSIONS: Our algorithm has demonstrated high accuracy in classifying epithelial tumors and its benefits as an assistance tool, which can serve as a potential screening aid system in diagnosing gastric biopsy specimens.
Assuntos
Aprendizado Profundo , Mucosa Gástrica/patologia , Interpretação de Imagem Assistida por Computador/métodos , Patologistas/estatística & dados numéricos , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/estatística & dados numéricos , Estudos de Viabilidade , Feminino , Mucosa Gástrica/diagnóstico por imagem , Gastroscopia/estatística & dados numéricos , Humanos , Interpretação de Imagem Assistida por Computador/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Prospectivos , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias Gástricas/patologiaRESUMO
Cutaneous radiation injury (CRI) is a skin injury caused by exposure to high dose ionizing radiation (IR). Diagnosis and treatment of CRI is difficult due to its initial clinically latent period and the following inflammatory bursts. Early detection of CRI before clinical symptoms will be helpful for effective treatment, and various optical methods have been applied with limitations. Here we show that optical coherence tomography angiography (OCTA) could detect changes in the skin during the latent period in CRI mouse models non-invasively. CRI was induced on the mouse hindlimb with exposure to various IR doses and the injured skin regions were imaged longitudinally by OCTA until the onset of clinical symptoms. OCTA detected several changes in the skin including the skin thickening, the dilation of large blood vessels, and the irregularity in vessel boundaries. Some of OCTA findings were confirmed by histology. The study results showed that OCTA could be used for early CRI detection.