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OBJECTIVE: Paragangliomas of the urinary bladder (UBPGLs) are rare neuroendocrine tumours and pose a diagnostic and surgical challenge. It remains unclear what factors contribute to a timely presurgical diagnosis. The purpose of this study is to identify factors contributing to missing the diagnosis of UBPGLs before surgery. DESIGN, PATIENTS AND MEASUREMENTS: A total of 73 patients from 11 centres in China, and 51 patients from 6 centres in Europe and 1 center in the United States were included. Clinical, surgical and genetic data were collected and compared in patients diagnosed before versus after surgery. Logistic regression analysis was used to identify clinical factors associated with initiation of presurgical biochemical testing. RESULTS: Among all patients, only 47.6% were diagnosed before surgery. These patients were younger (34.0 vs. 54.0 years, p < .001), had larger tumours (2.9 vs. 1.8 cm, p < .001), and more had a SDHB pathogenic variant (54.7% vs. 11.9%, p < .001) than those diagnosed after surgery. Patients with presurgical diagnosis presented with more micturition spells (39.7% vs. 15.9%, p = .003), hypertension (50.0% vs. 31.7%, p = .041) and catecholamine-related symptoms (37.9% vs. 17.5%, p = .012). Multivariable logistic analysis revealed that presence of younger age (<35 years, odds ratio [OR] = 6.47, p = .013), micturition spells (OR = 6.79, p = .007), hypertension (OR = 3.98, p = .011), and sweating (OR = 41.72, p = .013) increased the probability of initiating presurgical biochemical testing. CONCLUSIONS: Most patients with UBPGL are diagnosed after surgery. Young age, hypertension, micturition spells and sweating are clues in assisting to initiate early biochemical testing and thus may establish a timely presurgical diagnosis.
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Paraganglioma , Neoplasias da Bexiga Urinária , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/diagnóstico , Feminino , Masculino , Adulto , Paraganglioma/diagnóstico , Paraganglioma/cirurgia , Europa (Continente) , Estados Unidos , Idoso , ChinaRESUMO
AIM: To examine association between subgingival microbial signatures and levels of cognitive impairment in older adults. MATERIALS AND METHODS: We analysed subgingival plaque samples and 16S ribosomal RNA sequences for microbiota among 165 participants (normal controls [NCs]: 40, subjective cognitive decline [SCD]: 40, mild cognitive impairment [MCI]: 49 and dementia: 36). RESULTS: The bacterial richness was lower among individuals with worse cognitive function, and subgingival microbial communities differed significantly among the four groups. Declining cognitive function was associated with decreasing relative abundance of genera Capnocytophaga, Saccharibacteria_genera_incertae_sedis, Lautropia and Granulicatella, and increasing abundance of genus Porphyromonas. Moreover, there were differentially abundant genera among the groups. Random forest model based on subgingival microbiota could distinguish between cognitive impairment and NC (AUC = 0.933, 95% confidence interval 0.873-0.992). Significant correlations were observed between oral microbiota and sex, Montreal Cognitive Assessment (MoCA) score and Mini-Mental State Examination score. Partial correlation analysis showed that Leptotrichia and Burkholderia were closely negatively associated with the MoCA score after adjusting for multiple covariates. Gene function was not significantly different between SCD and NC groups, whereas three homozygous genes were altered in MCI patients and two in dementia patients. CONCLUSIONS: This is the first study to demonstrate an association between the composition, function and metabolic pathways of subgingival microbiota and different levels of cognitive function among older individuals. Future cohort studies should assess its diagnostic usefulness for cognitive impairment.
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Disfunção Cognitiva , Microbiota , Humanos , Idoso , Feminino , Masculino , Disfunção Cognitiva/microbiologia , Demência/microbiologia , Cognição/fisiologia , RNA Ribossômico 16S/análise , Gengiva/microbiologia , Placa Dentária/microbiologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou maisRESUMO
OBJECTIVES: A considerable number of patients are diagnosed with prostate cancer (PCa) by transurethral resection of the prostate (TURP). We aimed to evaluate whether radical prostatectomy (RP) brings survival benefits for these patients, especially in the elderly with advanced PCa. PATIENTS AND METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database to obtain PCa cases diagnosed with TURP. After the propensity matching score (PSM) for case matching, univariate, multivariate, and subgroup analyses were performed to investigate whether RP impacts the survival benefit. RESULTS: 4,677 cases diagnosed with PCa by TURP from 2010 to 2019 were obtained, including 1,313 RP patients and 3,364 patients with no RP (nRP). 9.6% of RP patients had advanced PCa. With or without PSM, cancer-specific mortality (CSM) and overall mortality (OM) were significantly reduced in the RP patients compared to the nRP patients, even for older (> 75 ys.) patients with advanced stages (all p < 0.05). Except for RP, younger age (≤ 75 ys.), being married, and earlier stage (localized) contributed to a significant reduction of CSM risk (all p < 0.05). These survival benefits had no significant differences among patients of different ages, married or single, and at different stages (all p for interaction > 0.05). CONCLUSIONS: Based on this retrospective population-matched study, we first found that in patients diagnosed with PCa by TURP, RP treatment may lead to a survival benefit, especially a reduction in CSM, even in old aged patients (> 75 ys.) with advanced PCa.
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Prostatectomia , Neoplasias da Próstata , Programa de SEER , Ressecção Transuretral da Próstata , Humanos , Masculino , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/diagnóstico , Idoso , Prostatectomia/métodos , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Estadiamento de Neoplasias , Taxa de Sobrevida/tendênciasRESUMO
Diet can regulate systemic inflammation, which may play an important role in the development and progression of cognitive impairment and dementia. To explore the relationship between the dietary inflammatory potential and cognitive ability. A total of 2307 adults aged 60 years or older were recruited from the Fujian Provincial Hospital (Fujian, China). Dietary inflammatory properties were analyzed using the energy-adjusted dietary inflammatory index (E-DII). The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to assess cognitive function. Logistic regression and restricted cubic spline (RCS) were fit to assess the associations between variables. The MCI subjects with the highest E-DII scores had a higher risk of AD compared to subjects with the lowest E-DII scores (OR = 1.98, 95%CI = 1.49-2.64, P for trend < 0.001). Subjects with the highest E-DII levels were at increased risk of cognitive impairment compared to those with the lowest E-DII levels (OR = 1.56, 95%CI = 1.25-1.93, P for trend < 0.001). The link between E-DII and cognitive impairment was significant in a nonlinear dose response analysis (P for nonlinear = 0.001). Higher E-DII scores were associated with an increased risk of developing AD or cognitive impairment. These findings may contribute to the effective prevention of cognitive impairment by constructing a multidisciplinary synergistic prevention strategy and controlling dietary inflammation levels.
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INTRODUCTION: DNA methylation regulates gene transcriptional functions in the pathogenesis of malignant diseases. In prostate cancer, several tumor suppressors are known to be tumor specifically methylated. METHODS: In this study, 450K methylation data and mRNA expression data were accessed from The Cancer Genome Atlas-Prostate Adenocarcinoma database and analyzed bioinformatically. Methylation-specific PCR was used to examine the methylation condition in AOX1 promoter. qRT-PCR was applied to measure the mRNA expression of AOX1. Western blot was employed to detect the expressions of AOX1 and the EMT associated proteins. Transwell and scratch healing assays were used to examine the invasive and migratory abilities of the prostate cancer cells respectively. RESULTS: AOX1 was lowly expressed and hypermethylated in the prostate cancer tissues and cells. Also, AOX1 was downregulated at protein level in prostate cancer cells. Knocking down AOX1 could promote cell migration and invasion in the prostate cancer cells. By using a DNA methylation inhibitor, 5-AzadC was found to promote the expression of AOX1 and reverse the promoting effects of short interfering RNA against AOX1 on cell migration and invasion. CONCLUSION: This study suggested that DNA methylation and low AOX1 level might be biomarkers for prostate cancer.
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Metilação de DNA , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/patologia , Movimento Celular/genética , Próstata/patologia , RNA Mensageiro , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética , Aldeído Oxidase/genética , Aldeído Oxidase/metabolismoRESUMO
Bladder cancer is a common malignancy in the urinary system. Defects of drug molecules in bladder during treatment, such as passive diffusion, rapid clearance of periodic urination, poor adhesion and permeation abilities, lead to low delivery efficiency of conventional drugs and high recurrence rate of disease. In this study, we designed multi-responsive mesoporous polydopamine (PDA) composite nanorods cooperating with nano-enzyme and photosensitiser for intensive immunotherapy of bladder cancer. The strongly adhesive mesoporous PDA with wheat germ agglutinin on nanoparticles could specifically adhere to epithelial glycocalyx and made the nanoparticles aggregate in urinary pathways. Meanwhile, 2,3-dimethylmaleic anhydride could be hydrolysed in acidic conditions of tumour microenvironment, giving it a positive charge (charge reversal), which is more amenable to enter cancer cells. Afterwards, manganese dioxide nanorods could catalyse the reaction of excess H2 O2 in tumour microenvironment to generate active oxygen, so as to change the hypoxic environment in tumour, and achieve a pH-responsive for slow release of PD-L1. After the ICG was irradiated by infrared light, a large amount of singlet oxygen was generated, thereby enhancing the therapeutic effect and reducing toxicity in vivo. Besides, mesoporous PDA with indocyanine green photothermal agent could have a local heat up quickly under the near-infrared light to kill cancer cells, thereby enhancing therapeutic efficacy. Accordingly, this mesoporous PDA composite nanorods shed a light on bladder tumour treatment.
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Nanopartículas , Nanotubos , Neoplasias da Bexiga Urinária , Antígeno B7-H1 , Linhagem Celular Tumoral , Doxorrubicina , Humanos , Imunoterapia , Verde de Indocianina/metabolismo , Indóis , Nanopartículas/uso terapêutico , Fármacos Fotossensibilizantes , Polímeros , Espécies Reativas de Oxigênio , Oxigênio Singlete , Microambiente Tumoral , Neoplasias da Bexiga Urinária/terapia , Aglutininas do Germe de TrigoRESUMO
BACKGROUND Chromophobe renal cell carcinoma (ChRCC) is difficult to diagnose preoperatively. We investigated multiple detector computed tomography (MDCT) plain scan and multi-phase CT enhancement features to aid ChRCC preoperative diagnosis. MATERIAL AND METHODS MDCT data of patients with pathologically confirmed ChRCC were retrospectively analyzed. We calculated the ratios of the CT value for the solid part of the mass to those of the renal cortex, aorta, and inferior vena cava. These ratios were designated as L01-3 for the CT plain scan images, La1-3 for the cortical phase, Lv1-3 for the nephrographic phase, and Lp1-3 for the pelvic phase. We classified the masses into types I, II, III, and IV by type of enhancement. RESULTS Sixty-eight masses were included and divided into 3 groups by tumor size (groups A, B, and C). Percentages of calcification, central scars, and small vessel signs were significantly different during the cortical phase for masses in all groups (all P<0.01). Significant differences in enhancement were observed between tumors with severe and mild degrees of enhancement (P<0.01); and among La1, Lv1, and Lp1; La2, Lv2, and Lp2; and La3, Lv3, and Lp3 after enhancement during the cortical, nephrographic, and renal pelvic phases (all P<0.01). The most common type of mass enhancement was type II, followed by type I, and differences between these 2 types were significant (P<0.001). CONCLUSIONS Although the MDCT features for ChRCC are diverse, MDCT helped preoperatively diagnose ChRCC. Multiple MDCT features are needed to improve the accuracy of preoperative diagnosis.
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Carcinoma de Células Renais/diagnóstico , Neoplasias Renais/diagnóstico , Tomografia Computadorizada Multidetectores/métodos , Adulto , Idoso , Aorta/patologia , Carcinoma de Células Renais/patologia , Diagnóstico Diferencial , Feminino , Humanos , Rim/patologia , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Veia Cava Inferior/patologiaRESUMO
BACKGROUND: Prostate cancer is one of the most common malignancies in men. Protein ubiquitination is an important mechanism for regulating protein activity and level in vivo. We aimed to study the mechanism of SEPT6 and UBC action in prostate cancer to identify new targets. METHODS: The ubiquitin-protein and the ubiquitin coding gene UBA52, UBA80, UBB, and UBC expressions were detected in clinical tissues and cells. Overexpression and knockdown of UBC were performed in prostate cancer DU145 cells. Cell Counting Kit 8 (CCK-8) assay was performed to detect cell proliferation. Cell cycle at 24 h was detected by flow cytometry. Clonal formation assay was used to measure cell clone number. Immunofluorescence (IF) was performed to detect the colocalization of SEPT6 and UBC in prostate cancer cells. Next, we overexpressed or knocked down SEPT6 expression in DU145 cells. Pearson correlation coefficient was applied to analyze the relationship between SEPT6 and UBC in prostate cancer tissue. oe-SEPT6+oe-UBC coexpressing cells were constructed to detect the upstream and downstream relationship between SEPT6 and UBC on prostate cancer cells. The tumor formation experiment was performed to explore SEPT6/UBC effect on prostate cancer. RESULTS: UBC was upregulated in prostate cancer tissues and cells. Overexpression of UBC promoted cell survival and proliferation. IF revealed the colocalization of SEPT6 and UBC in prostate cancer cells. UBC expression decreased after oe-SEPT6, while increased after sh-SEPT6, indicating that UBC was downstream of SEPT6. Pearson correlation coefficient analysis showed that SEPT6 was negatively correlated with UBC in prostate cancer tissues. SEPT6 as an upstream gene of UBC regulated prostate cancer cell behavior through UBC. The tumor formation experiment showed that SEPT6 could inhibit tumor growth. CONCLUSION: In general, SEPT6 inhibited UBC expression, thereby reducing the overall ubiquitination level, affecting the expression level of downstream cell proliferation-related genes, and then affecting the progression of prostate cancer.
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Neoplasias da Próstata , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Próstata/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , UbiquitinaçãoRESUMO
Objective: To evaluate the modified Zhang's 'three-level' technique of retroperitoneal laparoscopic adrenalectomy (RLA) to treat adrenal lesions for patients with BMI of 25-30 Kg/m2. Methods: A retrospective analysis was performed in all patients with BMI of 25-30 Kg/m2 in our hospital from January 2014 to December 2019. Those who underwent laparoscopic adrenal surgery were divided into two groups on the basis of the technique used: the Zhang's technique (the ZT group) and the modified technique (the MT group). Results: Herein, 170 operations were included (ZT, 91 patients; MT, 79 patients). RLA was successfully performed in all of them. Compared with the ZT group patients, the MT group patients showed shorter operation time (p = 0.007), lesser intraoperative blood loss (p = 0.023), shorter operation time, earlier postoperative diet recovery (p < 0.001), shorter postoperative drainage time (p < 0.001) and shorter postoperative hospitalization period (p = 0.001). It was also worth noting that the unplanned total adrenalectomy rate was significantly less in the MT group than in the ZT group (0% vs. 10.8%, p = 0.020). There was no significant difference in the complications between the two groups (3.3% vs. 2.5%, p = 0.567). Conclusions: We found that MT was a beneficial retroperitoneal laparoscopic treatment for adrenal lesions in patients who had a BMI of 25-30 Kg/m2. It may provide a reference for the treatment of adrenal surgical diseases in such patients.
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Doenças das Glândulas Suprarrenais/cirurgia , Adrenalectomia/métodos , Laparoscopia/métodos , Sobrepeso/complicações , Doenças das Glândulas Suprarrenais/complicações , Adrenalectomia/efeitos adversos , Adulto , Idoso , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Índice de Massa Corporal , Feminino , Humanos , Laparoscopia/efeitos adversos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Espaço Retroperitoneal/cirurgia , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate the safety and efficacy of scrotoscope in diagnosis and treatment of testicular and epididymal diseases. METHODS: From September 2010 to March 2012, a total of 75 patients, aged 15-64 years (mean age is 42.4 years) were included in this study. Based on ultrasonagraphy before surgery, 12 cases were diagnosed as testicular torsion and 63 cases were diagnosed as epididymal mass. All the patients underwent scrotoscope examination or scrotoscope epididymectomy. A small scrotal incision of 1.0 cm was performed. Bluntly dissection was then performed through the scrotal layer until the tunica sac was disclosed. We used cystoscope or resectoscope as scrotoscope. Keeping the drip fusion of isotonic solution inflowing, the scrotum was maintained appropriate distended. The tunica sac wall including parietal and visceral tunica was checked. The testis, epididymis was then examined from the anterior, posterior and both lateral aspects to find out any potential pathology. The operation time of scrotoscope, postoperative complications, surgery record, ultrasound and pathology results were collected from medical record. Visual analog pain scale (range from 0 points to 10 points, 0 represent no pain, 10 represent the most severe pain) was used to assess scrotal pain. The postoperative complications, recurrence and pain relief were evaluated, the accuracy rates of the diagnosis was compared between scrotoscope and ultrasound based on pathology results. RESULTS: All the patients were successfully performed scrotoscope except one because of inflammatory adhesion. The average time of the operation was 34.3±5.8 minutes, and no serious complications, such as severe edema, hematoma, testicular hydrocele and wound infection occurred. The accuracy rate of scrotoscope and ultrasound for the diagnosis of testicular torsion was 100% vs. 66.7%, and the accuracy rate of scrotoscope and ultrasound for the diagnosis of epididymal mass was 76.2% vs. 58.7%. In the study, 63 patients received scrotoscope epididymectomy, the visual analogue pain score before surgery was 7.1±0.8, 6 months after operation, and the pain score was 2.4±0.6. CONCLUSION: Scrotoscope is safe. There are no serious complications such as severe edema, hematoma, testicular hydrocele and wound infection occurred. Scrotoscope is superior to ultrasound for diagnosis of testicular torsion and epididymal mass. Scrotoscope epididymectomy is effective for pain relief, especially for patients with epididymal cyst.
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Doenças dos Genitais Masculinos/diagnóstico , Escroto , Procedimentos Cirúrgicos Urológicos Masculinos/instrumentação , Adolescente , Adulto , Epididimo/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Dor , Medição da Dor , Complicações Pós-Operatórias , Próstata , Recidiva , Torção do Cordão Espermático/diagnóstico , Testículo , Procedimentos Cirúrgicos Urológicos Masculinos/métodos , Ducto Deferente , Adulto JovemRESUMO
Objective: To analyze the influencing factors of male cutaneous melanoma (CM) patients dying from genitourinary diseases (GUD). Methods: We searched the surveillance, epidemiology, and end results (SEER) database and extracted data on male CM patients according to the inclusion and exclusion criteria, including male patients whose cause of death was CM (cohort A) or GUD (cohort B). Comparisons between the two cohorts were performed before and after propensity score matching (PSM). An interaction analysis between age and year of diagnosis was also conducted. Cox regression analysis were performed to find the risk factors for death from GUD. Results: Seven thousand seventy-eight CM patients were included, including 6415 (90.6%) in cohort A and 663 (9.4%) in cohort B. Compared with cohort A, cohort B patients were older (median age 74 ys. vs 65 ys.) and were more under the localized stage and had longer survival time no matter before or after PSM (all p<0.001). The stage was an inhibitory factor for cohort B (p <0.001). After PSM, only age and year of diagnosis were found to be cohort B's promoting factors (p<0.001). The interaction analysis showed that older patients diagnosed in later years (2009-2020) had a higher risk of dying from GUD compared to those diagnosed earlier (p<0.05). Patients with a later year of diagnosis (2009-2020) had a lower median survival time than patients with an earlier year of diagnosis (2000-2008) (p<0.001). When the patient's year of diagnosis was earlier (2000-2008), older patients (>75 ys.) had a higher risk of dying from GUD than younger patients (≤75 ys.) (p<0.001). Conclusion: We first reported a significant interaction between age and year of diagnosis in male CM patients dying from GUD, highlighting the increased risk in older patients diagnosed more recently. We may pay attention to the possibility of dying from genitourinary diseases for CM patients.
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BACKGROUND: The basic helix-loop-helix family member e41 (BHLHE41) is frequently dysregulated in tumors and plays a crucial role in malignant progression of various cancers. Nevertheless, its specific function and underlying mechanism in bladder cancer (BCa) remain largely unexplored. METHODS: The expression levels of BHLHE41 in BCa tissues and cells were examined by qRT-PCR and western blot assays. BCa cells stably knocking down or overexpressing BHLHE41 were constructed through lentivirus infection. The changes of cell proliferation, cell cycle distribution, migration, and invasion were detected by CCK-8, flow cytometry, wound healing, transwell invasion assays, respectively. The expression levels of related proteins were detected by western blot assay. The interaction between BHLHE41 and PYCR1 was explored by co-immunoprecipitation analysis. RESULTS: In this study, we found that BHLHE41 was lowly expressed in bladder cancer tissues and cell lines, and lower expression of BHLHE41 was associated with poor overall survival in bladder cancer patients. Functionally, by manipulating the expression of BHLHE41, we demonstrated that overexpression of BHLHE41 significantly retarded cell proliferation, migration, invasion, and induced cell cycle arrest in bladder cancer through various in vitro and in vivo experiments, while silence of BHLHE41 caused the opposite effect. Mechanistically, we showed that BHLHE41 directly interacted with PYCR1, decreased its stability and resulted in the ubiquitination and degradation of PYCR1, thus inactivating PI3K/AKT signaling pathway. Rescue experiments showed that the effects induced by BHLHE41 overexpression could be attenuated by further upregulating PYCR1. CONCLUSION: BHLHE41 might be a useful prognostic biomarker and a tumor suppressor in bladder cancer. The BHLHE41/PYCR1/PI3K/AKT axis might be a potential therapeutic target for bladder cancer intervention.
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Proliferação de Células , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Pirrolina Carboxilato Redutases , Transdução de Sinais , Neoplasias da Bexiga Urinária , delta-1-Pirrolina-5-Carboxilato Redutase , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/genética , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirrolina Carboxilato Redutases/metabolismo , Pirrolina Carboxilato Redutases/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Movimento Celular/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Camundongos , Animais , MasculinoRESUMO
ALK-positive Histiocytosis (ALK-HSs) is a recently identified rare clinical entity characterized by tissue histiocytic alterations associated with ALK gene rearrangement. Clinical presentations can be solitary, multifocal, or systemic (involving multiple sites and organs). Due to limited reported cases, there is inadequate understanding of this disease. This report presents a case of ALK-HSs in a 71-year-old male patient who presented with hematuria for one week. Imaging studies conducted at an external hospital showed multiple lesions in the penis, bilateral testes, back skin, and the third lumbar vertebra. Histopathological findings included spindle and histiocytic cell proliferation with mild or indistinct cellular atypia, interstitial infiltration of lymphocytes, plasma cells, foamy histiocytes, and fibrous tissue proliferation. Immunohistochemistry of the lesion cells revealed positivity for CD68, CD163, ALK1, ALK (D5F3), and Vimentin. FISH testing indicated ALK gene separation in the lesion cells. NGS testing identified the fusion genes KIF5B(NM_004521) and ALK(NM_004304) in the lesion cells. We combined the characteristics of this case with a review of the literature to enhance our understanding of this rare clinical entity.
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BACKGROUND: LINC00887 has been mentioned in several articles regarding its involvement in various cancers like nasopharyngeal carcinoma, lung cancer and glioma. However, the mechanism of LINC00887 in the malignant progression of clear cell renal cell carcinoma (ccRCC) is still unclear. The topic of our study is mainly centered on exploring how LINC00887 exactly affects ccRCC malignant progression. METHODS: The bioinformatics method predicted the downstream TF and target genes of LINC00887 by the "LncRNA-transcription factor (TF)-Gene" triplet model. RNA immunoprecipitation, chromatin immunoprecipitation analysis, and Dual-luciferase reporter assay determined the regulatory relationship between LINC00887 and its downstream genes. The LINC00887 expression and its downstream gene expression in ccRCC cells were examined by qRT-PCR and Western blot. The effect of LINC00887-SPI1-CD70 modulation axis on proliferative transfer, cell stemness and T cell chemotaxis of ccRCC cells was examined in cellular and animal experiments. RESULTS: Our research demonstrated an upregulation of LINC00887 in ccRCC, which facilitated tumor growth and stemness in vivo. In addition, LINC00887 could upregulate the CD70 expression by recruiting transcriptional factor SPI1. The results of in vitro experiments illustrated that the LINC00887-SPI1-CD70 regulatory axis facilitated ccRCC malignant progression by promoting cell stemness and hindering T-cell chemotaxis. CONCLUSION: LINC00887, by recruiting SPI1, activated CD70 transcription, thereby propelling malignant progression and cell stemness and suppressing T cell chemotaxis in ccRCC. Based on our findings, we believed that the LINC00887-SPI1-CD70 regulatory axis had the potential to be a critical breakthrough for treating ccRCC.
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Carcinoma de Células Renais , Neoplasias Renais , Animais , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/patologia , Quimiotaxia , Fatores de Transcrição/genética , Imunoprecipitação da Cromatina , Linfócitos T/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genéticaRESUMO
Cancer-directed surgeries (CDS) play a crucial role in prostate cancer (PCa) management along with possible survival and therapeutic benefits. However, barriers such as socioeconomic factors may affect patients' decision of refusing recommended CDS. This study aimed to uncover risk factors and the impact on survival associated with CDS refusal. We retrospectively reviewed the Surveillance, Epidemiology, and End Results database for patients diagnosed with PCa between 2000 and 2019. Multiple sociodemographic and clinical characteristics were extracted to assess predictors for physicians' surgical recommendations and patients' surgical refusal, respectively. Propensity score matching was performed to balance the covariates. The impact of surgical refusal on mortality risk was also investigated. A total of 185,540 patients were included. The physician's recommendation of CDS was significantly influenced by the patient's age, race, income, home location, diagnosis year, Gleason score, prostate-specific antigen (PSA), and TNM stage. About 5.6% PCa patients refused CDS, most of whom were older, non-White race, lack of partners, living outside of metropolitan areas, with higher PSA or lower clinical TNM stage. Patients who refused CDS had an increased risk of cancer-specific mortality and overall mortality than those who performed CDS. Physicians may weigh a host of sociodemographic and clinical factors prior to making a CDS recommendation. Patients' refusal of recommended CDS affected survival and was potentially modifiable by certain sociodemographic factors. Physicians should fully consider the hindrances behind patients' CDS refusal to improve patient-doctor shared decision-making, guide patients toward the best alternative and achieve better outcomes.
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Pontuação de Propensão , Neoplasias da Próstata , Recusa do Paciente ao Tratamento , Humanos , Masculino , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/mortalidade , Idoso , Fatores de Risco , Pessoa de Meia-Idade , Estudos Retrospectivos , Recusa do Paciente ao Tratamento/estatística & dados numéricos , Programa de SEER , Prostatectomia , Antígeno Prostático Específico/sangue , Gradação de Tumores , Estadiamento de Neoplasias , Fatores SocioeconômicosRESUMO
Although overall survival data are still premature, the PROpel study found radiological progression-free survival (PFS) benefits of abiraterone and olaparib in patients with metastatic castration-resistant prostate cancer (mCRPC). However, for patients who have not been genetically tested or lack BRCA1/2 mutations (BRCAm), this combination therapy has been questioned as a first-line conventional treatment for mCRPC, mainly due to significant health economics and side effects. In our retrospective study, we found that treatment with low-dose abiraterone plus olaparib as a late-line treatment for mCRPC could lead to prostate-specific antigen (PSA) and symptom PFS in selective cases even without BRCAm. The median PSA-PFS was 8 months (IQR: 6.5-11.5), with a median follow-up duration of 39.0 months (IQR: 27.5-64.5). Gene tests were conducted in all patients, identifying non-BRCA mutations through ctDNA testing (24%), tumor tissue testing (12%), or both (64%). Adverse events occurred in 72% of patients, with 16% experiencing Grade ≥ 3 events. Common adverse events included anemia (64%), decreased appetite (48%), and fatigue (25%). Our findings support low-dose abiraterone plus olaparib as a potential option for mCRPC patients without BRCAm, offering manageable safety and efficacy profiles.
Assuntos
Androstenos , Protocolos de Quimioterapia Combinada Antineoplásica , Proteína BRCA1 , Proteína BRCA2 , Ftalazinas , Piperazinas , Neoplasias de Próstata Resistentes à Castração , Humanos , Ftalazinas/administração & dosagem , Ftalazinas/uso terapêutico , Masculino , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Piperazinas/administração & dosagem , Piperazinas/uso terapêutico , Piperazinas/efeitos adversos , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Proteína BRCA2/genética , Androstenos/administração & dosagem , Androstenos/uso terapêutico , Projetos Piloto , Proteína BRCA1/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Mutação , Antígeno Prostático Específico/sangue , Idoso de 80 Anos ou mais , Intervalo Livre de ProgressãoRESUMO
Background: Chronic inflammatory stimulation is a major risk factor for mild cognitive impairment. Mushroom consumption and inflammatory factors may play an important role in the pathogenesis of mild cognitive impairment. Additionally, consuming mushrooms can reduce the levels of inflammatory cytokines and preserve cognitive function. Therefore, this study aimed to investigate the relationship between mushroom consumption and serum inflammatory cytokines and mild cognitive impairment (MCI). Methods: Binary logistic regression was used to determine the relationship between mushroom consumption and MCI in 550 participants. Subsequently, mediation analysis was used to analyze the relationship between mushroom consumption, inflammatory factors, and the Montreal Cognitive assessment (MoCA) score in 248 participants. Results: Mushroom consumption was associated with MCI (odds ratio = 0.623, 95% confidence interval = 0.542-0.715, P < 0.001). The association between mushroom intake and MCI was mediated by interleukin-6 (IL-6) and hypersensitive C-reactive protein (hs-CRP), and the MoCA score was 12.76% and 47.59%, respectively. Conclusion: A high intake of mushrooms was associated with a low risk of MCI. Serum inflammatory factors including IL-6 and hs-CRP play a partial mediating role between mushroom intake and the MoCA score, and the underlying mechanism needs to be further explored.
Assuntos
Agaricales , Proteína C-Reativa , Disfunção Cognitiva , Inflamação , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína C-Reativa/metabolismo , China , Estudos Transversais , População do Leste Asiático , Interleucina-6/sangue , Fatores de Risco , DietaRESUMO
Langerhans cell sarcoma (LCS) is a rare malignancy of dendritic cells and usually results in a poor oncological outcome. Thus, LCS is usually given a positive administration. Herein, we presented the first case of primary LCS in the urinary bladder staged T1N0M0 and treated by TURBT and short-term local chemotherapy. Our experience in this unique case may suggest that LCS in the urinary bladder with a non-muscle-invasive stage may be managed according to the treatment model of non-muscle-invasive urothelial carcinoma of the urinary bladder.