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1.
Am J Speech Lang Pathol ; 33(4): 1986-2001, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38838249

RESUMO

PURPOSE: Prior work has identified weaknesses in commonly used indices of lexical diversity in spoken language samples, such as type-token ratio (TTR) due to sample size and elicitation variation, we explored whether TTR and other diversity measures, such as number of different words/100 (NDW), vocabulary diversity (VocD), and the moving average TTR would be more sensitive to child age and clinical status (typically developing [TD] or developmental language disorder [DLD]) if samples were obtained from standardized prompts. METHOD: We utilized archival data from the norming samples of the Test of Narrative Language and the Edmonton Narrative Norms Instrument. We examined lexical diversity and other linguistic properties of the samples, from a total of 1,048 children, ages 4-11 years; 798 of these were considered TD, whereas 250 were categorized as having a language learning disorder. RESULTS: TTR was the least sensitive to child age or diagnostic group, with good potential to misidentify children with DLD as TD and TD children as having DLD. Growth slopes of NDW were shallow and not very sensitive to diagnostic grouping. The strongest performing measure was VocD. Mean length of utterance, TNW, and verbs/utterance did show both good growth trajectories and ability to distinguish between clinical and typical samples. CONCLUSIONS: This study, the largest and best controlled to date, re-affirms that TTR should not be used in clinical decision making with children. A second popular measure, NDW, is not measurably stronger in terms of its psychometric properties. Because the most sensitive measure of lexical diversity, VocD, is unlikely to gain popularity because of reliance on computer-assisted analysis, we suggest alternatives for the appraisal of children's expressive vocabulary skill.


Assuntos
Linguagem Infantil , Transtornos do Desenvolvimento da Linguagem , Testes de Linguagem , Vocabulário , Humanos , Pré-Escolar , Criança , Masculino , Feminino , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Testes de Linguagem/normas , Fatores Etários , Reprodutibilidade dos Testes
2.
J Ovarian Res ; 17(1): 73, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566208

RESUMO

Ovarian cancer is a leading cause of death among gynecologic tumors, often detected at advanced stages. Metabolic reprogramming and increased lipid biosynthesis are key factors driving cancer cell growth. Stearoyl-CoA desaturase 1 (SCD1) is a crucial enzyme involved in de novo lipid synthesis, producing mono-unsaturated fatty acids (MUFAs). Here, we aimed to investigate the expression and significance of SCD1 in epithelial ovarian cancer (EOC). Comparative analysis of normal ovarian surface epithelial (NOSE) tissues and cell lines revealed elevated SCD1 expression in EOC tissues and cells. Inhibition of SCD1 significantly reduced the proliferation of EOC cells and patient-derived organoids and induced apoptotic cell death. Interestingly, SCD1 inhibition did not affect the viability of non-cancer cells, indicating selective cytotoxicity against EOC cells. SCD1 inhibition on EOC cells induced endoplasmic reticulum (ER) stress by activating the unfolded protein response (UPR) sensors and resulted in apoptosis. The addition of exogenous oleic acid, a product of SCD1, rescued EOC cells from ER stress-mediated apoptosis induced by SCD1 inhibition, underscoring the importance of lipid desaturation for cancer cell survival. Taken together, our findings suggest that the inhibition of SCD1 is a promising biomarker as well as a novel therapeutic target for ovarian cancer by regulating ER stress and inducing cancer cell apoptosis.


Assuntos
Neoplasias Ovarianas , Estearoil-CoA Dessaturase , Feminino , Humanos , Estearoil-CoA Dessaturase/metabolismo , Apoptose , Estresse do Retículo Endoplasmático , Carcinoma Epitelial do Ovário , Lipídeos
3.
Cancer Sci ; 115(5): 1536-1550, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38433313

RESUMO

Ovarian cancer is a lethal gynecologic cancer mostly diagnosed in an advanced stage with an accumulation of ascites. Interleukin-6 (IL-6), a pro-inflammatory cytokine is highly elevated in malignant ascites and plays a pleiotropic role in cancer progression. Mitochondria are dynamic organelles that undergo fission and fusion in response to external stimuli and dysregulation in their dynamics has been implicated in cancer progression and metastasis. Here, we investigate the effect of IL-6 on mitochondrial dynamics in ovarian cancer cells (OVCs) and its impact on metastatic potential. Treatment with IL-6 on ovarian cancer cell lines (SKOV3 and PA-1) led to an elevation in the metastatic potential of OVCs. Interestingly, a positive association was observed between dynamin-related protein 1 (Drp1), a regulator of mitochondrial fission, and IL-6R in metastatic ovarian cancer tissues. Additionally, IL-6 treatment on OVCs was linked to the activation of Drp1, with a notable increase in the ratio of the inhibitory form p-Drp1(S637) to the active form p-Drp1(S616), indicating enhanced mitochondrial fission. Moreover, IL-6 treatment triggered the activation of ERK1/2, and inhibiting ERK1/2 mitigated IL-6-induced mitochondrial fission. Suppressing mitochondrial fission through siRNA transfection and a pharmacological inhibitor reduced the IL-6-induced migration and invasion of OVCs. This was further supported by 3D invasion assays using patient-derived spheroids. Altogether, our study suggests the role of mitochondrial fission in the metastatic potential of OVCs induced by IL-6. The inhibition of mitochondrial fission could be a potential therapeutic approach to suppress the metastasis of ovarian cancer.


Assuntos
Dinaminas , Interleucina-6 , Sistema de Sinalização das MAP Quinases , Dinâmica Mitocondrial , Neoplasias Ovarianas , Humanos , Feminino , Dinâmica Mitocondrial/efeitos dos fármacos , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Interleucina-6/metabolismo , Dinaminas/metabolismo , Linhagem Celular Tumoral , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metástase Neoplásica , Mitocôndrias/metabolismo , Receptores de Interleucina-6/metabolismo , Movimento Celular/efeitos dos fármacos
4.
Vasc Specialist Int ; 40: 10, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38527946

RESUMO

Purpose: : Endotension is a rare late complication characterized by an increase in sac size without any type of endoleak following endovascular aortic aneurysm repair (EVAR). Due to its rarity, few studies have demonstrated the mechanism behind and the management of endotension. In this study, we aimed to better understand the treatment and the long-term outcome of endotension in a single-center cohort. Materials and Methods: : This study was designed for a retrospective review of the patients diagnosed with endotension between January 2006 and December 2017. The study patients were categorized into two groups (primary versus secondary) based on the presence of any type of endoleak before the diagnosis of endotension. We collected data related to endotension treatment, intraoperative findings, and long-term outcomes. Results: : In a cohort of 15 patients diagnosed with endotension following EVAR, eight were classified into the primary endotension (PE) group without prior endoleak, and seven exhibited secondary endotension (SE). Among the eight PE patients, endovascular intervention for a preemptive purpose was conducted in six patients; however, three (50%) showed continuous sac expansion and finally received open conversion. Overall, eight patients (five in PE and three in SE) underwent open conversion, and one (12.5%) presented with an undetected endoleak during the operative findings. Postoperative morbidity was observed in three patients with no operative mortality. Conclusion: : Endotension can be managed initially through simple observation for changes on serial images, along with preemptive endovascular intervention. However, surgical intervention should be considered for patients with specific indications including continuous aneurysm sac enlargement, presence of symptoms, suspicions of migration of stent-graft with endoleak, and infection.

6.
Sci Rep ; 14(1): 781, 2024 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191895

RESUMO

The major causes of death in patients with abdominal aortic aneurysm (AAA) are cardiovascular disease and cancer. The purpose of this study was to evaluate the effect of AAA on long-term survival in lung cancer patients. All patient data with degenerative type AAA and lung cancer over 50 years of age during the period 2009 to 2018 was collected retrospectively from a National Health Insurance Service (NHIS) administrative database and matched to lung cancer patients without AAA by age, sex, metastasis, and other comorbidities. Mortality rate was compared between the groups. A total of 956 AAA patients who could be matched with patients without AAA were included, and 3824 patients in the matched group were used for comparison. Patients with AAA showed higher risk of death compared with the matched cohort (adjusted hazard ratio (HR) 1.14, 95% confidence interval (CI) 1.06-1.23, p < 0.001). When compared to a matched group of untreated AAA patients, patients with of history of AAA exhibited a significantly increased risk of overall mortality [HR (95%CI) 1.219 (1.113-1.335), p < .001, adjusted HR (95% CI) 1.177 (1.073-1.291), p = .001]. By contrast, mortality risk of AAA patients treated either by endovascular abdominal aortic repair or open surgical repair was not significantly different from that of the matched group (p = 0.079 and p = 0.625, respectively). The mortality risk was significantly higher when AAA was present in lung cancer patients, especially in patients with unrepaired AAA, suggesting the need for continuous cardiovascular risk management.


Assuntos
Aneurisma da Aorta Abdominal , Doenças Cardiovasculares , Neoplasias Pulmonares , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Aneurisma da Aorta Abdominal/epidemiologia , Bases de Dados Factuais
7.
J Korean Med Sci ; 38(39): e321, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37821088

RESUMO

BACKGROUND: Ruptured abdominal aortic aneurysm (rAAA) is a serious complication of abdominal aortic aneurysm associated with high operative mortality and morbidity rates. The present study evaluated the perioperative and long-term outcomes of Korean patients with rAAA based on national health insurance claims data. METHODS: The National Health Insurance Service (NHIS) database was searched retrospectively to identify patients with rAAA who underwent endovascular aneurysm repair (EVAR) and open surgical repair (OSR) from 2009 to 2018. Perioperative (≤ 30 days), early postoperative (≤ 3 month), and long-term (> 3 month) survival, reinterventions, and complications were assessed. RESULTS: The search identified 1,034 patients with rAAA, including 594 who underwent EVAR and 440 who underwent OSR. When the study period was divided into two, the total numbers of patients with rAAA, patients who underwent EVAR, and octogenarians were higher during the second half. The perioperative mortality rate was 29.8% in the EVAR and 35.0% in the OSR group (P = 0.028). Hartmann's procedure for bowel infarction was performed more frequently in the OSR than in the EVAR group (adjusted odds ratio, 6.28; 95% confidence interval [CI], 2.33-21.84; P = 0.001), but other complication rates did not differ significantly. All-cause mortality during the entire observation period did not differ significantly in the EVAR and OSR groups (adjusted hazard ratio, 1.17; 95% CI, 0.98-1.41; P = 0.087). Abdominal aortic aneurysm-related reintervention rate was significantly lower in the OSR group (adjusted hazard ratio, 0.31; 95% CI, 0.14-0.70; P = 0.005). CONCLUSION: Although EVAR showed somewhat superior perioperative outcomes for rAAA, the long-term outcomes of EVAR after excluding initial 3 months were significantly worse than OSR. When anatomically feasible for both treatments, the perioperative mortality risk and reasonable prospects of long-term survival should be considered in rAAA.


Assuntos
Aneurisma da Aorta Abdominal , Ruptura Aórtica , Implante de Prótese Vascular , Procedimentos Endovasculares , Idoso de 80 Anos ou mais , Humanos , Aneurisma da Aorta Abdominal/cirurgia , Estudos Retrospectivos , Procedimentos Endovasculares/efeitos adversos , Complicações Pós-Operatórias/etiologia , Implante de Prótese Vascular/efeitos adversos , Ruptura Aórtica/cirurgia , Ruptura Aórtica/etiologia , Resultado do Tratamento , Fatores de Risco
8.
Vasc Specialist Int ; 39: 23, 2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37667821

RESUMO

Radical nephrectomy with tumor thrombectomy for advanced renal cell carcinoma is an oncologically relevant approach that can achieve long-term survival even in the presence of distant metastases. However, the surgical techniques pose significant challenges. The objective of this clinical review was to present technical recommendations for tumor thrombectomy in the vena cava to facilitate surgical treatment. Transesophageal echocardiography is required to prepare for this procedure. Cardiopulmonary bypass should be considered when the tumor thrombus has invaded the cardiac chamber and clamping is not feasible because of the inability to milk the intracardiac chamber thrombus in the caudal direction. Prior to performing a cavotomy, it is crucial to clamp the contralateral renal vein and infrarenal and suprahepatic inferior vena cava (IVC). If the suprahepatic IVC is separated from the surrounding tissue, it can be gently pulled down toward the patient's leg until the lower margin of the atrium becomes visible. Subsequently, the tumor thrombus should be carefully pulled downward to a position where it can be clamped. Implementing the Pringle maneuver to reduce blood flow from the hepatic veins to the IVC during IVC cavotomy is simpler than clamping the hepatic veins. Sequential clamping is a two-stage method of dividing thrombectomy by clamping the IVC twice, first suprahepatically and then midretrohepatically. This sequential clamping technique helps minimize hypotension status and the Pringle maneuver time compared to single clamping. Additionally, a spiral cavotomy can decrease the degree of primary closure narrowing. The oncological prognoses of patients can be improved by incorporating these technical recommendations.

9.
Ann Surg Treat Res ; 105(1): 37-46, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37441324

RESUMO

Purpose: Although endovascular aneurysm repair (EVAR) has been shown to be superior to open surgical repair (OSR) for abdominal aortic aneurysm (AAA) treatment, no large-scale studies in the Korean population have compared outcomes and costs. Methods: The National Health Insurance Service database in Korea was screened to identify AAA patients treated with EVAR or OSR from 2008 to 2019. Perioperative, early postoperative, and long-term survival were compared, as were reinterventions and complications. Patients were followed-up through 2020. Results: Of the 13,631 patients identified, 2,935 underwent OSR and 10,696 underwent EVAR. Perioperative mortality rate was lower in the EVAR group (4.2% vs. 8.0%, P < 0.001) even after excluding patients with ruptured AAA (2.7% vs. 3.3%, P = 0.003). However, long-term mortality rate per 100 person-years was significantly higher in the EVAR than in the OSR group (9.0 vs. 6.4, P < 0.001), and all-cause mortality was lower in the OSR group (hazard ratio, 0.9; 95% confidence interval, 0.87-0.97, P = 0.008). EVAR had a higher AAA-related reintervention rate per 100 person-years (1.75 vs. 0.52), and AAA-related reintervention costs were almost 10-fold higher with EVAR (US dollar [USD] 6,153,463) than with OSR (USD 624,216). Conclusion: While EVAR may have short-term advantages, OSR may provide better long-term outcomes and cost-effectiveness for AAA treatment in the Korean population, under the medical expense system in Korea.

10.
J Clin Med ; 12(13)2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37445354

RESUMO

Large-scale population studies of the incidence of and mortality from abdominal aortic aneurysm (AAA) are needed to develop healthcare policies and priorities. The aim of this study was to estimate the incidence of AAA and the all-cause mortality from it among Koreans aged ≥50 years from 2009 to 2018 using data from the Korean National Health Insurance System Database. The crude and standardized incidence and all-cause mortality of the disease among patients with unruptured AAA were calculated. A total of 73,933 AAA patients were identified. The overall incidence of AAA in adults ≥50 years during the study period was 37.5 per 100,000 population (49.7 per 100,000 in men and 26.8 per 100,000 in women), with an increase from 32.33 per 100,000 persons in 2009 to 46.85 per 100,000 in 2018. The crude all-cause mortality rate of patients with untreated AAA was 21.26/100 person-years in 2009 and 8.87/100 person-years in 2018, with decreasing trends observed both in men and women. This nationwide study showed that the incidence of AAA in Koreans aged ≥50 years in 2018 was 63.40 per 100,000 in men and 32.07 per 100,000 in women. The overall rates were 0.06% and 0.03%, respectively, with an increasing trend. Mortality has decreased in both treated and untreated patients. The observed increase in incidence suggests a rising burden of AAA in the Korean population, particularly among men. The decreasing mortality rates may indicate improvements in the management and treatment of AAA over the study period.

11.
Ann Surg Treat Res ; 104(6): 339-347, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37337602

RESUMO

Purpose: This study aimed to review our experience with the explantation of infected endovascular aneurysm repair (EVAR) grafts. Methods: This single-center, retrospective, observational study analyzed the data of 12 consecutive patients who underwent infected aortic stent graft explantation following EVAR between January 1, 2010 and December 31, 2019, of which 11 underwent in situ graft reconstruction following graft removal. The presentation symptoms, infection route, original pathology of abdominal aortic aneurysms (AAA), graft materials, and clinical outcomes were analyzed. Results: Six patients underwent total explantation, whereas 5 underwent removal of only the fabric portions. For in situ reconstructions, prosthetic grafts and banked allografts were used in 8 and 3 patients, respectively. Four mechanisms of graft infection were noted in 11 patients: 4 had bacteremia from systemic infections, 3 had persistent infections following EVAR of primary infected AAA, 3 had ascending infections from adjacent abscesses, and 1 had an aneurysm sac erosion resulting in an aortoenteric fistula. No infection-related postoperative complications or reinfections occurred during the mean 65.27-month (standard deviation, ±52.51) follow-up period. One patient died postoperatively because of the rupture of the proximal aortic wall pseudoaneurysm that had occurred during forceful bare stent removal. Conclusion: Regardless of graft material, in situ graft reconstruction is safe for interposition in treating an infected aortic stent graft following EVAR. In our experience, the residual bare stent is no longer a risk factor for reinfection. Therefore, it is important not to injure the proximal aortic wall when removing the bare stent by force.

12.
J Pharmacol Exp Ther ; 386(2): 212-223, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37188531

RESUMO

Recent advances in the RNA delivery system have facilitated the development of a separate field of RNA therapeutics, with modalities including mRNA, microRNA (miRNA), antisense oligonucleotide (ASO), small interfering RNA, and circular (circRNA) that have been incorporated into oncology research. The main advantages of the RNA-based modalities are high flexibility in designing RNA and rapid production for clinical screening. It is challenging to eliminate tumors by tackling a single target in cancer. In the era of precision medicine, RNA-based therapeutic approaches potentially constitute suitable platforms for targeting heterogeneous tumors that possess multiple sub-clonal cancer cell populations. In this review, we discussed how synthetic coding and non-coding RNAs, such as mRNA, miRNA, ASO, and circRNA, can be applied in the development of therapeutics. SIGNIFICANCE STATEMENT: With development of vaccines against coronavirus, RNA-based therapeutics have received attention. Here, the authors discuss different types of RNA-based therapeutics potentially effective against tumor that are highly heterogeneous giving rise to resistance and relapses to the conventional therapeutics. Moreover, this study summarized recent findings suggesting combination approaches of RNA therapeutics and cancer immunotherapy.


Assuntos
MicroRNAs , Neoplasias , Humanos , RNA/genética , RNA Circular/genética , RNA Circular/uso terapêutico , RNA Interferente Pequeno/uso terapêutico , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Oligonucleotídeos Antissenso/genética , Oligonucleotídeos Antissenso/uso terapêutico , RNA Mensageiro
13.
Front Oncol ; 12: 872995, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35785211

RESUMO

Background: A positive relationship was reported between metabolic syndrome and the risk of endometrial cancer. Studies on the relationship between metabolic syndrome and endometrial cancer have been mainly conducted in post-menopausal women. We aimed to investigate the risk of endometrial cancer according to metabolic syndrome and menopausal status using the Korean nationwide population-based cohort. Methods: We enrolled 2,824,107 adults (endometrial cancer group; N = 5,604 and control group; N= 2,818,503) from the Korean National Health Insurance Service checkup database from January 1 to December 31, 2009. The median follow-up duration was 8.37 years. Metabolic syndrome was diagnosed as having at least three of the following five components: abdominal obesity, hypertriglyceridemia, low levels of high-density lipoprotein cholesterol, raised blood pressure, and hyperglycemia. Multivariate Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) to estimate endometrial cancer risk. Results: The endometrial cancer risk was higher in the metabolic syndrome group than that in the non-metabolic syndrome group (HR, 1.362; 95% CI, 1.281-1.449). The association between metabolic syndrome and endometrial cancer risk was significant in the premenopausal subgroup (HR, 1.543; 95% CI, 1.39-1.713) and postmenopausal subgroup (HR, 1.306; 95% CI, 1.213-1.407). The incidence of endometrial cancer was more closely related to metabolic syndrome components in the pre-menopausal subgroup than those in the post-menopausal subgroup (for waist circumference, blood pressure, triglycerides and high-density lipoprotein cholesterol, all p for interaction <0.0001 respectively, and for fasting blood glucose, p for interaction 0.0188). The incidence of endometrial cancer positively correlated with the number of metabolic syndrome components (log-rank p <0.0001). Conclusion: Our large population-based cohort study in Korean women suggests that metabolic syndrome and its accumulated components may be risk factors for endometrial cancer, particularly in the pre-menopausal women.

14.
Front Oncol ; 12: 852260, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35646632

RESUMO

The poor prognosis of ovarian cancer patients mainly results from a lack of early diagnosis approaches and a high rate of relapse. Only a very modest improvement has been made in ovarian cancer patient survival with traditional treatments. More targeted therapies precisely matching each patient are strongly needed. The aberrant activation of Wnt/ß-catenin signaling pathway plays a fundamental role in cancer development and progression in various types of cancer including ovarian cancer. Recent insight into this pathway has revealed the potential of targeting Wnt/ß-catenin in ovarian cancer treatment. This study aims to investigate the effect of CWP232291, a small molecular Wnt/ß-catenin inhibitor on ovarian cancer progression. Various in vitro, in vivo and ex vivo models are established for CWP232291 testing. Results show that CWP232291 could significantly attenuate ovarian cancer growth through inhibition of ß-catenin. Noticeably, CWP232291 could also s suppress the growth of cisplatin-resistant cell lines and ovarian cancer patient-derived organoids. Overall, this study has firstly demonstrated the anti-tumor effect of CWP232291 in ovarian cancer and proposed Wnt/ß-catenin pathway inhibition as a novel therapeutic strategy against ovarian cancer.

15.
J Ovarian Res ; 15(1): 70, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35668443

RESUMO

BACKGROUND: Mitochondrial dynamics (e.g. fission/fusion) play an important role in controlling chemoresistance in representative gynecologic malignancies, ovarian and cervical cancer. Processing the long form of Optic atrophy (L-Opa)1 is a distinctive character of mitochondrial fragmentation, associated with chemosensitivity. Here, we examined the role of prohibitin (Phb)1 in increasing L-Opa1 processing via the regulating mitochondrial protease, Oma1 and its direct interaction with p-p53 (ser15) and pro-apoptotic Bcl-2 antagonist/killer (Bak) 1 in the signaling axis and if this phenomenon is associated with prognosis of patients. METHODS: We compared Cisplatin (CDDP)-induced response of mitochondrial dynamics, molecular interaction among p-p53 (ser15)-Phb1-Bak, and chemoresponsiveness in paired chemosensitive and chemoresistant gynecologic cancer cells (ovarian and cervical cancer cell lines) using western blot, immunoprecipitation, sea horse, and immunofluorescence. Translational strategy with proximity ligation assessment in phb1-p-p53 (ser15) in human ovarian tumor sections further confirmed in vitro finding, associated with clinical outcome. RESULTS: We report that: (1) Knock-down of Phb1 prevents Cisplatin (cis-diamine-dichloroplatinum; CDDP) -induced changes in mitochondrial fragmentation and Oma1 mediated cleavage, and Opa1 processing; (2) In response to CDDP, Phb1 facilitates the p-p53 (ser15)-Phb1-Bak interaction in mitochondria in chemosensitive gynecologic cancer cells but not in chemoresistant cells; (3) Akt overexpression results in suppressed p-p53(Ser15)-Phb1 interaction and dysregulated mitochondrial dynamics, and (4) Consistent with in vitro findings, proximity ligation assessment (PLA) in human ovarian tumor sections demonstrated that p-p53(ser15)-Phb1-Bak interaction in mitochondria is associated with better chemoresponsiveness and clinical outcome of patients. Determining the molecular mechanisms by which Phb1 facilitates mitochondrial fragmentation and interacts with p53 may advance the current understanding of chemoresistance and pathogenesis of gynecologic cancer. CONCLUSION: Determining the key molecular mechanisms by which Phb1 facilitates the formation of p-p53 (ser15)-Bak-Phb1 and its involvement in the regulation of mitochondrial dynamics and apoptosis may ultimately contribute to the current understanding of molecular and cellular basis of chemoresistance in this gynecologic cancer.


Assuntos
Antineoplásicos , Neoplasias dos Genitais Femininos , Neoplasias Ovarianas , Neoplasias do Colo do Útero , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Dinâmica Mitocondrial , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Proibitinas , Proteína Supressora de Tumor p53/metabolismo
16.
Cancer Lett ; 542: 215735, 2022 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-35569696

RESUMO

Ovarian cancer is mostly diagnosed at advantaged stages due to the lack of early diagnostic biomarkers. The common metastasis pattern is characterized by peritoneal dissemination with a formation of malignant ascites. Extracellular vesicles (EVs) are emerging as promising clinical biomarkers in liquid biopsy. Here, we aimed to investigate robust liquid biopsy-based EV miRNA biomarkers for ovarian cancer diagnosis and metastasis regulation. EVs were isolated from malignant ascites and plasma of ovarian cancer patients as well as the benign control counterparts of patients with benign gynecologic diseases. EV small RNA sequencing identified a panel of eight miRNAs (miR-1246, miR-1290, miR-483, miR-429, miR-34b-3p, miR-34c-5p, miR-145-5p, miR-449a) based on dysregulated miRNAs overlapped in the ascites and plasma subset. The ovarian cancer EV miRNA (OCEM) signature developed based on these eight miRNAs demonstrated high diagnostic accuracy in our in-house dataset and multiple public datasets across diverse clinical samples (blood, tissue and urine). In addition, malignant ascites-derived EVs could significantly facilitate the aggressive property of ovarian cancer cells and boost the growth of ascites-derived organoids. Notably, miR-1246 and miR-1290 shuttled in malignant ascites-derived EVs were identified to promote the invasion and migration of ovarian cancer cells through regulating a common target RORα.


Assuntos
Vesículas Extracelulares , MicroRNAs , Neoplasias Ovarianas , Ascite/diagnóstico , Ascite/genética , Biomarcadores Tumorais/genética , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/genética , Vesículas Extracelulares/genética , Vesículas Extracelulares/patologia , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia
17.
PLoS One ; 17(5): e0268077, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35511926

RESUMO

OBJECTIVE: Diameter is currently the only screening and diagnostic criterion for asymptomatic aneurysms. Therefore, aortic and lower-extremity arterial diameter has diagnostic, therapeutic, and prognostic importance. We aimed to determine aortic and lower-extremity arterial reference diameters in a general population and compare them according to age, sex, and other characteristics. METHODS: We evaluated consecutive 3,692 patients who underwent computed tomography as part of a general health checkup from 2015-2019 in a single tertiary center. Aortic and lower-extremity arterial diameters and the most important factor related to arterial diameters were evaluated. RESULTS: The mean diameter of the abdominal aorta was 17.490 ± 2.110 mm, while that of the common iliac artery was 10.851 ± 1.689 mm. The mean diameter of the abdominal aorta was 18.377 ± 1.766 mm in men and 15.884 ± 1.694 mm in women. Significant intersex differences were observed for all mean diameters and lengths. Multilinear regression analysis showed that age, sex, and body surface area impacted mean diameters of all measured sites except aorta and common iliac artery length. Between male and female patients matched for body surface area, there were significant intersex differences for all measured sites, except for common iliac artery length. CONCLUSIONS: The mean diameter of the abdominal aorta in this healthy cohort was 17.490 ± 2.110 mm overall, 18.377 ± 1.766 mm in men, and 15.884 ± 1.694 mm in women. Arterial diameter increased with male sex, older age, and increased body surface area, and aortic diameters were larger in men than in women with the same body surface area.


Assuntos
Aorta Abdominal , Aneurisma da Aorta Abdominal , Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/diagnóstico , Superfície Corporal , Estudos de Coortes , Feminino , Humanos , Artéria Ilíaca/diagnóstico por imagem , Masculino , Tomografia Computadorizada por Raios X
18.
Endocrinol Metab (Seoul) ; 37(6): 879-890, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36604958

RESUMO

BACKGRUOUND: Cross-talk between mitogen-activated protein kinase and estrogen has been reported; however, the role of BRAFV600E in the estrogen responsiveness of thyroid cancer is unknown. We elucidated the effect of BRAFV600E on the estrogen-induced increase in metastatic potential in thyroid cancer. METHODS: Using a pair of cell lines, human thyroid cell lines which harbor wild type BRAF gene (Nthy/WT) and Nthy/BRAFV600E (Nthy/V600E), the expression of estrogen receptors (ERs) and estrogen-induced metastatic phenotypes were evaluated. Susceptibility to ERα- and ERß-selective agents was evaluated to confirm differential ER expression. ESR expression was analyzed according to BRAFV600E status and age (≤50 years vs. >50 years) using The Cancer Genome Atlas (TCGA) data. RESULTS: Estradiol increased the ERα/ERß expression ratio in Nthy/V600E, whereas the decreased ERα/ERß expression ratio was found in Nthy/WT. BRAFV600E-mutated cell lines showed a higher E2-induced increase in metastatic potential, including migration, invasion, and anchorage-independent growth compared with Nthy/WT. An ERα antagonist significantly inhibited migration in Nthy/V600E cells, whereas an ERß agonist was more effective in Nthy/WT. In the BRAFV600E group, ESR1/ESR2 ratio was significantly higher in younger age group (≤50 years) compared with older age group (>50 years) by TCGA data analysis. CONCLUSION: Our data show that BRAFV600E mutation plays a crucial role in the estrogen responsiveness of thyroid cancer by regulating ER expression. Therefore, BRAFV600E might be used as a biomarker when deciding future hormone therapies based on estrogen signaling in thyroid cancer patients.


Assuntos
Receptores de Estrogênio , Neoplasias da Glândula Tireoide , Humanos , Idoso , Pessoa de Meia-Idade , Receptores de Estrogênio/genética , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/genética , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Estrogênios/farmacologia , Mutação
19.
PLoS One ; 16(12): e0260690, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34855851

RESUMO

OBJECTIVES: This study aimed to compare the quality of life and cost effectiveness between endovascular aneurysm repair (EVAR) and open surgical repair (OSR) in young patients with abdominal aortic aneurysm (AAA). DESIGN: This was a single-center, observational, and retrospective study. MATERIALS AND METHODS: A retrospective analysis was conducted of patients with AAA, who were <70 years old and underwent EVAR or OSR between January 2012 and October 2016. Only patients with aortic morphology that was suitable for EVAR were enrolled. Data on the complication rates, medical expenses, and expected quality-adjusted life years (QALYs) were collected, and the cost per QALY at three years was compared. RESULTS: Among 90 patients with aortic morphology who were eligible for EVAR, 37 and 53 patients underwent EVAR and OSR, respectively. No significant differences were observed in perioperative cardiovascular events and death between the two groups. However, during the follow-up period, patients undergoing OSR showed a significantly lower complication rate (hazard ratio [HR] = 0.11; P = .021). From the three-year cost-effectiveness analysis, the total sum of costs was significantly lower in the OSR group (P < .001) than that in the EVAR group, and the number of QALYs was superior in the OSR group (P = .013). The cost per QALY at three years was significantly lower in the OSR group than that in the EVAR group (mean: $4038 vs. $10 137; respectively; P < .001). CONCLUSIONS: OSR had lower complication rates and better cost-effectiveness than EVAR Among young patients with feasible aortic anatomy.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Procedimentos Cirúrgicos Eletivos , Procedimentos Endovasculares , Anos de Vida Ajustados por Qualidade de Vida , Idoso , Aneurisma da Aorta Abdominal/patologia , Análise Custo-Benefício , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Procedimentos Cirúrgicos Eletivos/economia , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/economia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
20.
Sci Rep ; 11(1): 21359, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725390

RESUMO

This retrospective observational study investigated the long-term prevalence of new-onset cardiovascular disease (CVD) and the predictive role of atherosclerotic plaque in the aorta and iliac arteries for CVD in postoperative colorectal cancer (CRC) patients who received surgical treatment between 2014 and 2015. CVD included coronary or cerebrovascular diseases which required treatment and new-onset CVD included peri-and postoperatively diagnosed CVDs or aggravated CVDs that required additional treatment during follow-up. Of the 2,875 patients included in this study, the prevalence of CVD was 8.9% (255/2875) and 141 (4.9%) developed new-onset CVD. Maximum arterial stenosis in the aorta or iliac arteries occurred in 40.8 ± 18.6% of patients with new-onset CVD and 11.6 ± 13.8% of patients without new-onset CVD (p < 0.001). The mean new-onset CVD-free survival time in patients with > 30% and < 30% stenoses were 52.5 [95% confidence intervals (CIs) 50.0-54.9] and 66.5 (95% CIs 66.2-66.8) months, respectively (p < 0.001). The area under the receiver operating characteristic curve of the maximal arterial stenosis for new-onset CVD was 0.911. These results suggest that CRC patients are at risk for developing new-onset CVD, which is associated with reduced survival. Atherosclerotic burden in the aorta or both iliac arteries may help predict future CVD events.


Assuntos
Doenças Cardiovasculares/etiologia , Neoplasias Colorretais/cirurgia , Placa Aterosclerótica/etiologia , Idoso , Neoplasias Colorretais/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco
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