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1.
Mol Carcinog ; 63(3): 461-478, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38018692

RESUMO

Metabolic abnormalities are one of the important factors in bladder cancer (BCa) progression and microenvironmental disturbance. As an important product of purine metabolism, uric acid's (UA) role in BCa metabolism and immunotherapy remains unclear. In this study, we conducted a retrospective analysis of a cohort comprising 39 BCa patients treated with PD-1 and 169 patients who underwent radical cystectomy at Shanghai Tenth People's Hospital. Kaplan-Meier curves and Cox regression analysis showed that the prognosis of patients with high UA is worse (p = 0.007), and high UA is an independent risk factor for cancer specific survival in patients with BCa (p = 0.025). We established a hyperuricemia mouse model with BCa subcutaneous xenografts in vivo. The results revealed that the subcutaneous tumors of hyperuricemia mice had a greater weight and volume in comparison with the control group. Through flow cytometric analysis, the proportion of CD8+ and CD4+ T cells in these subcutaneous tumors was seen to decline significantly. We also evaluated the relationship of UA and BCa by muti-omic analysis. UA related genes were significantly increased in the CD8+ T cell of non-responders to immunotherapy by single-cell sequencing. An 11-gene UA related signature was constructed and the risk score negatively correlated with various immune cells and immune checkpoints. Finally, a nomogram was established using a UA related signature to forecast the survival rate of patients with BCa. Collectively, this study demonstrated that UA was an independent prognostic biomarker for BCa and was associated with worse immunotherapy response.


Assuntos
Hiperuricemia , Neoplasias da Bexiga Urinária , Humanos , Animais , Camundongos , Ácido Úrico , Multiômica , Estudos Retrospectivos , China , Neoplasias da Bexiga Urinária/genética , Microambiente Tumoral
2.
Acta Pharmacol Sin ; 45(7): 1366-1380, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38538717

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disease, and its prevalence is increasing. Currently, no effective therapies for PD exist. Marine-derived natural compounds are considered important resources for the discovery of new drugs due to their distinctive structures and diverse activities. In this study, tetrahydroauroglaucin (TAG), a polyketide isolated from a marine sponge, was found to have notable neuroprotective effects on MPTP/MPP+-induced neurotoxicity. RNA sequencing analysis and metabolomics revealed that TAG significantly improved lipid metabolism disorder in PD models. Further investigation indicated that TAG markedly decreased the accumulation of lipid droplets (LDs), downregulated the expression of RUBCN, and promoted autophagic flux. Moreover, conditional knockdown of Rubcn notably attenuated PD-like symptoms and the accumulation of LDs, accompanied by blockade of the neuroprotective effect of TAG. Collectively, our results first indicated that TAG, a promising PD therapeutic candidate, could suppress the accumulation of LDs through the RUBCN-autophagy pathway, which highlighted a novel and effective strategy for PD treatment.


Assuntos
Metabolismo dos Lipídeos , Fármacos Neuroprotetores , Animais , Metabolismo dos Lipídeos/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Homeostase/efeitos dos fármacos , Poríferos/química , Camundongos , Camundongos Endogâmicos C57BL , Autofagia/efeitos dos fármacos , Masculino , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Policetídeos/farmacologia , Humanos
3.
Angew Chem Int Ed Engl ; 63(40): e202407640, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38898602

RESUMO

Photocatalysis holds a pivotal position in modern organic synthesis, capable of inducing novel reactivities under mild and environmentally friendly reaction conditions. However, the merger of photocatalysis and transition-metal-catalyzed asymmetric C-H activation as an efficient and sustainable method for the construction of chiral molecules remains elusive and challenging. Herein, we develop a cobalt-catalyzed enantioselective C-H activation reaction enabled by visible-light photoredox catalysis, providing a synergistic catalytic strategy for the asymmetric dearomatization of indoles with high levels of enantioselectivity (96 % to >99 % ee). Mechanistic studies indicate that the excited photocatalyst was quenched by divalent cobalt species in the presence of Salox ligand, leading to the formation of catalytically active chiral Co(III) complex. Moreover, stoichiometric reactions of cobaltacycle intermediate with indole suggest that the irradiation of visible light also play a critical role in the dearomatization step.

4.
Mol Carcinog ; 62(2): 185-199, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36250643

RESUMO

The relationship between metabolism and immune microenvironment remains to be studied in bladder cancer (BCa). We aimed to construct a metabolic-associated signature for prognostic prediction and investigate its relationship with the immune microenvironment in BCa. The RNA expression of metabolism associated genes was obtained from a combined data set including The Cancer Genome Atlas, GSE48075, and GSE13507 to divide BCa patients into different clusters. A metabolic-associated signature was constructed using the differentially expressed genes between clusters in the combined data set and validated in the IMvigor210 trial and our center. The composition of tumor-infiltrating immune cells (TIICs) was evaluated using the single-sample Gene Set Variation Analysis. BCa patients in Cluster A or high-risk level were associated with advanced clinicopathological features and poor survival outcomes. The percentage of high-risk patients was significantly lower in patients responding to anti-PD-L1 treatment. Compared with low-risk patients, the IC50 values of cisplatin and gemcitabine were significantly lower in high-risk patients. Thiosulfate transferase (TST) and S100A16 were significantly associated with clinicopathological features and prognosis. Downregulation of TST promoted BCa cell invasion, migration, and epithelial-to-mesenchymal transition, which are inhibited by downregulation of S100A16. CD8 + T cells, neutrophils, and dendritic cells had higher infiltration in the TST low-level and the S100A16 high-level. Furthermore, loss of function TST and S100A16 significantly affected the expression of PD-L1 and CD47. The metabolic-associated signature can stratify BCa patients into distinct risk levels with different immunotherapeutic susceptibility and survival outcomes. Metabolism disorder promoted the dysregulation of immune microenvironment, thus contributing to immunosuppression.


Assuntos
Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/genética , Regulação para Baixo , Cisplatino , Linfócitos T CD8-Positivos , Transição Epitelial-Mesenquimal , Microambiente Tumoral/genética
5.
Nutr Cancer ; 73(8): 1440-1447, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32691640

RESUMO

This study aims to investigate the specific predictive role of the preoperative Nutritional Risk Index (NRI) in oligometastatic prostate cancer (OM-PC) patients, who have undergone cytoreductive radical prostatectomy (cRP), and explored its prognostic index values. A total 89 OM-PC patients, who were identified between 2013 and 2019, were included in the present study. The Kaplan-Meier method and Cox regression analysis were used to separately assess the prostate specific antigen (PSA) progression-free survival (PFS). Overall accuracy was determined by analyzing the area under the receiver operating characteristic curve (AUC). The analysis of patients in these three different groups indicated that patients with lower NRI values were significantly associated with a higher Gleason score and more neoadjuvant androgen deprivation therapy (P < 0.05). In addition, the Kaplan-Meier curve analysis revealed that OM-PC patients in the preoperative high-risk group had shorter PSA-PFS (P < 0.001). Furthermore, the multivariate analysis further predicted that the high-risk NRI value is a common independent prognostic factor for shorter PSA-PFS (P < 0.001). Moreover, it was also observed that the AUC value of the NRI score was higher than other conventional nutritional indicators. The present study suggests that NRI can potentially be used as a new prognostic indicator for PSA-PFS for patients with OM-PC after cRP.


Assuntos
Procedimentos Cirúrgicos de Citorredução , Estado Nutricional , Neoplasias da Próstata , Antagonistas de Androgênios , Humanos , Masculino , Recidiva Local de Neoplasia , Antígeno Prostático Específico , Prostatectomia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/cirurgia
6.
Phytother Res ; 33(12): 3140-3152, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31452288

RESUMO

Multiphase pathological processes involve in Type 2 diabetes (T2DM)-induced nonalcoholic fatty liver disease (NAFLD). However, the therapies are quite limited. In the present study, the hepatoprotective effects and underlying mechanisms of quercetin in T2DM-induced NAFLD were investigated. T2DM-induced NAFLD and quercetin treatment models were established in vivo and in vitro. The results revealed that quercetin alleviated serum transaminase levels and markedly reduced T2DM-induced histological alterations of livers. Additionally, quercetin restored superoxide dismutase, catalase, and glutathione content in livers. Not only that, quercetin markedly attenuated T2DM-induced production of interleukin 1 beta, interleukin 6, and TNF-α. Accompanied by the restoration of the increased serum total bile acid (p = .0001) and the decreased liver total bile acid (p = .0005), quercetin could reduce lipid accumulation in the liver of db/db mice. Further mechanism studies showed that farnesoid X receptor 1/Takeda G-protein-coupled receptor 5 signaling pathways was involved in quercetin regulation of lipid metabolism in T2DM-induced NAFLD. In high D-glucose and free fatty acid cocultured HepG2 cells model, quercetin eliminated lipid droplets and restored the upregulated total cholesterol and triglyceride levels. Similar to the findings in mice, quercetin could also activate farnesoid X receptor 1/Takeda G-protein-coupled receptor 5 signaling pathway. These findings suggested that quercetin might be a potentially effective drug for the treatment of T2DM-induced NAFLD.


Assuntos
Antioxidantes/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Inflamação/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Quercetina/uso terapêutico , Animais , Antioxidantes/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Masculino , Camundongos , Quercetina/farmacologia , Transdução de Sinais
7.
Cell Physiol Biochem ; 51(2): 513-527, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30458442

RESUMO

BACKGROUND/AIMS: Increasing evidence showed that miR-1-3p plays a major role in malignant tumor progression. However, the specific biological function of miR-1-3p in bladder cancer is yet unknown. METHODS: The expression levels of miR-1-3p in bladder cancer tissues and cell lines were examined by qRT-PCR. Bisulfite sequencing PCR was used for DNA methylation analysis. The target of miR-1-3p was validated by a dual luciferase reporter assay, and the effects of miR-1-3p on phenotypic changes in bladder cancer cells were investigated in vitro and in vivo. RESULTS: The expression of miR-1-3p in bladder cancer cells was downregulated as compared to normal SV-HUC-1 cells. Also, the expression of miR-1-3p was significantly lower in bladder cancer tissues than the corresponding non-cancerous tissues. The methylation status of CpG islands was involved in the regulation of miR-1-3p expression. miR-1-3p inhibited the bladder cancer cell proliferation, migration, and invasion by directly targeting the 3'-UTR of glutaminase. It also exerted an anti-tumor effect by negatively regulating the glutaminase in a xenograft mouse model. Furthermore, GLS depletion resulted in the prolonged expression of γH2AX. CONCLUSION: Taken together, these results demonstrated that miR-1-3p acts as a tumor suppressor via regulation of glutaminase expression in bladder cancer progression, and miR-1-3p might represent a novel therapeutic target for the treatment of bladder cancer.


Assuntos
Proliferação de Células , Glutaminase/metabolismo , MicroRNAs/metabolismo , Regiões 3' não Traduzidas , Animais , Antagomirs/metabolismo , Antagomirs/uso terapêutico , Linhagem Celular Tumoral , Movimento Celular , Ilhas de CpG , Dano ao DNA , Metilação de DNA , Glutaminase/antagonistas & inibidores , Glutaminase/genética , Histonas/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
8.
BMC Cancer ; 18(1): 1141, 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30453909

RESUMO

BACKGROUND: This study aimed to explore hyper-O-linked N-acetylglucosaminylation (O-GlcNAcylation) with an elevation of the expression of O-linked-ß-N-acetylglucosamine transferase (OGT) in human bladder cancer. METHODS: Immunohistochemical staining for OGT and O-GlcNAcylation was performed in 20 paired human bladder cancer and adjacent normal tissues, as well as in human bladder cancer tissue microarrays (N = 169). The expression level of OGT and O-GlcNAcylation in cell lines were detected using the Western blot analysis. The effects of O-GlcNAcylation on the cell proliferation of bladder cancer were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clone formation assays. Cell apoptosis and cell cycle analysis were detected using flow cytometry. The autophagy of bladder cancer cells was investigated using the Western blot analysis, and GFP-LC3 plasmid was used to detect the autophagic flux. MTT assay was performed to detect the sensitivity of bladder cancer cells to cisplatin after OGT knockdown. RESULTS: The expression of OGT and the O-GlcNAcylation were upregulated in bladder cancer tissues and cell lines. O-GlcNAcylation and OGT were observed in nucleus and cytoplasm and found to be higher in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC). Reducing hyper-O-GlcNAcylation by OGT knockdown inhibited the proliferation of bladder cancer cells in vitro and xenograft tumor growth in vivo, triggered apoptosis, as well as led to cell cycle arrest. It also increased autophagy in bladder cancer cells. This study demonstrated increased autophagy pro-survival, but not pro-death. Reducing hyper-O-GlcNAcylation by OGT knockdown facilitated the chemosensitivity of bladder cancer cells to cis-platinum. CONCLUSIONS: The data indicated that hyper-O-GlcNAcylation enhanced oncogenic phenotypes and was involved in DNA damage response in bladder cancer.


Assuntos
Apoptose/fisiologia , Proliferação de Células/fisiologia , N-Acetilglucosaminiltransferases/metabolismo , Neoplasias da Bexiga Urinária/enzimologia , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Cisplatino/farmacologia , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , N-Acetilglucosaminiltransferases/genética , Processamento de Proteína Pós-Traducional , Interferência de RNA , Terapêutica com RNAi/métodos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/terapia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
9.
Front Genet ; 15: 1380746, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38798700

RESUMO

The increasing incidence and mortality of prostate cancer worldwide significantly impact the life span of male patients, emphasizing the urgency of understanding its pathogenic mechanism and associated molecular changes that regulate tumor progression for effective prevention and treatment. RNA modification, an important post-transcriptional regulatory process, profoundly influences tumor cell growth and metabolism, shaping cell fate. Over 170 RNA modification methods are known, with prominent research focusing on N6-methyladenosine, N7-methylguanosine, N1-methyladenosine, 5-methylcytidine, pseudouridine, and N4-acetylcytidine modifications. These alterations intricately regulate coding and non-coding RNA post-transcriptionally, affecting the stability of RNA and protein expression levels. This article delves into the latest advancements and challenges associated with various RNA modifications in prostate cancer tumor cells, tumor microenvironment, and core signaling molecule androgen receptors. It aims to provide new research targets and avenues for molecular diagnosis, treatment strategies, and improvement of the prognosis in prostate cancer.

10.
Mol Biomed ; 5(1): 36, 2024 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-39227479

RESUMO

Bladder cancer (BCa) stands out as a highly prevalent malignant tumor affecting the urinary system. The Sex determining region Y-box protein family is recognized for its crucial role in BCa progression. However, the effect of Sex determining region Y-box 7 (SOX7) on BCa progression has not been fully elucidated. Herein, RNA-sequencing, western blot (WB), immunohistochemistry (IHC), immunofluorescence (IF) and tissue microarray were utilized to assess SOX7 expression in vitro and in vivo. Additionally, SOX7 expression, prognosis, and SOX7 + cytoglobin (CYGB) score were analyzed using R software. In vitro and vivo experiments were performed with BCa cell lines to validate the effect of SOX7 knockdown and overexpression on the malignant progression of BCa. The results showed that SOX7 exhibits low expression in BCa. It functions in diverse capacities, inhibiting the proliferative, migratory, and invasive capabilities of BCa. In addition, the experimental database demonstrated that SOX7 binds to the promoter of DNA methyltransferase 3 beta (DNMT3B), leading to the transcriptional inhibition of DNMT3B. This subsequently results in a reduced methylation of CYGB promoter, ultimately inhibiting the tumor progression of BCa. SOX7 + CYGB scores were significantly linked to patient prognosis. In conclusion, SOX7 inhibits the malignant progression of BCa via the DNMT3B/CYGB axis. Additionally, the SOX7 + CYGB score is capable of predicting the prognostic outcomes of BCa patients. Therefore, SOX7 and CYGB may play an important role in the progression of bladder cancer, and they can be used as prognostic markers of bladder cancer patients.


Assuntos
DNA (Citosina-5-)-Metiltransferases , DNA Metiltransferase 3B , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Neoplasias da Bexiga Urinária , Animais , Feminino , Humanos , Masculino , Camundongos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Metilação de DNA , Camundongos Nus , Prognóstico , Regiões Promotoras Genéticas/genética , Fatores de Transcrição SOXF/genética , Fatores de Transcrição SOXF/metabolismo , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Citoglobina/genética , Citoglobina/metabolismo
11.
Heliyon ; 10(12): e32621, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38975179

RESUMO

Background: The exosome is a critical component of the intercellular communication., playing a vital role in regulating cell function. These small vesicles contain proteins, mRNAs, miRNAs, and lncRNAs, surrounded by lipid bilayer substances. Most cells in the human body can produce exosomes, released into various body fluids such as urine, blood, and cerebrospinal fluid. Bladder cancer is the most common tumor in the urinary system, with high recurrence and metastasis rates. Early diagnosis and treatment are crucial for improving patient outcomes. Methods: This study employed the PubMed search engine to retrieve publicly accessible data pertaining to urinary exosomes. Results: We summarize the origins and intricate biological characteristics of urinary exosomes, the introduction of research methodologies used in basic experiments to isolate and analyze these exosomes, the discussion of their applications and progress in the diagnosis and treatment of bladder cancer, and the exploration of the current limitations associated with using urinary exosomes as molecular biomarkers for diagnosing bladder cancer. Conclusion: Exosomes isolated from urine may be used as molecular biomarkers for early detection of bladder cancer.

12.
iScience ; 27(4): 109624, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38632984

RESUMO

Circular RNAs (circRNAs) play crucial biological functions in various tumors, including bladder cancer (BCa). However, the roles and underlying molecular mechanisms of circRNAs in the malignant proliferation of BCa are yet unknown. CircKDM1A was observed to be downregulated in BCa tissues and cells. Knockdown of circKDM1A promoted the proliferation of BCa cells and bladder xenograft growth, while the overexpression of circKDM1A exerts the opposite effect. The dual-luciferase reporter assay revealed that circKDM1A was directly bound to miR-889-3p, acting as its molecular sponge to downregulate CPEB3. In turn, the CPEB3 was bound to the CPE signal in p53 mRNA 3'UTR to stabilize its expression. Thus, circKDM1A-mediated CPEB3 downregulation inhibits the stability of p53 mRNA and promotes BCa malignant progression. In conclusion, circKDM1A functions as a tumor suppressor in the malignant proliferation of BCa via the miR-889-3p/CPEB3/p53 axis. CircKDM1A may be a potential prognostic biomarker and therapeutic target of BCa.

13.
BMJ Open ; 14(3): e080593, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38431292

RESUMO

INTRODUCTION: The classic way of diagnosing prostate cancer (PCa) is by conducting the 12-core systematic biopsy (SB). However, it has a low detection rate for clinically significant PCa (csPCa) and can lead to the detection of clinically insignificant PCa (cisPCa). Although MRI-transrectal ultrasound (MRI-TRUS) fusion targeted biopsy (TB) can effectively improve the detection rate of csPCa, it may still miss some cases. Therefore, we propose using a combination of TB and SB methods to enhance the detection rate of csPCa while minimising the detection rate of cisPCa. METHODS AND ANALYSIS: This study is a prospective, single-centre investigation that aims to assess and compare the detection rate of csPCa using MRI-TRUS fusion TB combined with SB versus TRUS 12-core SB alone. Biopsy-naïve men with suspected PCa will be subjected to multiparametric MRI. Patients with Prostate Imaging Reporting and Data System (V.2.1) score ≥3 will be enrolled in the TB-SB combination group. The sample size is established as 660 participants, considering a 10% drop-out rate. The primary outcome is the detection rate of csPCa in men without prior biopsy using MRI-TRUS fusion TB combined with the standard TRUS-guided 12-core SB method. CsPCa will be defined as International Society of Urological Pathology Grade ≥2. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee at the Shanghai Tenth People's Hospital, an affiliated hospital of Tongji University School of Medicine. The research results will be published in a peer-reviewed international journal. TRIAL REGISTRATION NUMBER: ChiCTR2000036089.


Assuntos
Biópsia Guiada por Imagem , Neoplasias da Próstata , Humanos , Masculino , China , Biópsia Guiada por Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Estudos Prospectivos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia
15.
Heliyon ; 9(1): e13012, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36704283

RESUMO

Recent evidence suggests that the human genitourinary microbiome plays a significant role in mediating the development and progression of urological tumors, including bladder cancer (BC). Clinicians widely recognize the role of Bacille Calmette Guérin (BCG), an attenuated Mycobacterium tuberculosis vaccine, in the management of intermediate- and high-risk NMIBC. However, compared to the large body of evidence on the gut microbiota and gastrointestinal tumors, limited information is available about the interaction between BC and the genitourinary microbiome. This is an expanding field that merits further investigation. Urologists will need to consider the potential impact of the microbiome in BC diagnosis, prevention of recurrence and progression, and treatment prospects in the future. This review highlights the approaches adopted for microbiome research and the findings and inadequacies of current research on BC.

16.
Int Urol Nephrol ; 55(7): 1709-1717, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37160485

RESUMO

Surgical manipulation has a risk of triggering the shedding of circulating tumor cells (CTCs) in patients with malignancies, However, perioperative change of circulating tumor cells in cytoreductive radical prostatectomy (CRP) for patients with oligometastatic hormone-sensitive prostate cancer (omHSPC) has not yet been well documented. This study aimed to assess whether CRP is a safe procedure for patients with omHSPC by monitoring the perioperative change of CTCs and investigating its impact on long-term oncologic outcomes. We have observed a significant decrease between the median CTC counts before and after surgery (6 vs. 4, p = 0.026). Comparing preoperative and postoperative CTC levels, seven patients increased (CTC increase group), one did not change and nineteen decreased (CTC non-increase group). PSA response rates in CTC increase group were lower than those in CTC non-increase group (73.0% vs 99.8%, p = 0.162), and nadir PSA was higher in CTC increase group (0.043 vs 0.003, p = 0.072). The CTC increase was positively correlated with the nadir PSA (r = 0.386, p = 0.047). The median follow-up period was 71.6 months, we found that there was no significant difference in clinical-pathological, operative variables or long-term oncologic outcomes between perioperative CTC increase and non-increase groups. In the entire cohort, the CTC level significantly decreased after surgery. There was no significant differences in long-term oncologic outcomes between the CTC increase and non-increase groups, implying that CRP potentially represents a safe procedure for the treatment of patients with omHSPC. The results need to be confirmed in a prospective large-scale clinical trial.


Assuntos
Células Neoplásicas Circulantes , Neoplasias da Próstata , Masculino , Humanos , Células Neoplásicas Circulantes/patologia , Antígeno Prostático Específico , Resultado do Tratamento , Estudos Prospectivos , Procedimentos Cirúrgicos de Citorredução , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Prostatectomia/métodos , Hormônios
17.
Front Cell Infect Microbiol ; 13: 1302870, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38235491

RESUMO

Background: Radical cystectomy and urinary diversion (UD) are gold standards for non-metastatic muscle-invasive bladder cancer. Orthotopic neobladder (or Studer), ileal conduit (or Bricker) and cutaneous ureterostomy (CU) are mainstream UD types. Little is known about urinary microbiological changes after UD. Methods: In this study, urine samples were collected from healthy volunteers and patients with bladder cancer who had received aforementioned UD procedures. Microbiomes of samples were analyzed using 16S ribosomal RNA gene sequencing, and microbial diversities, distributions and functions were investigated and compared across groups. Results: Highest urine microbial richness and diversity were observed in healthy controls, followed by Studer patients, especially those without hydronephrosis or residual urine, α-diversity indices of whom were remarkably higher than those of Bricker and CU groups. Studer UD type was the only independent factor favoring urine microbial diversity. The urine microflora structure of the Studer group was most similar to that of the healthy individuals while that of the CU group was least similar. Studer patients and healthy volunteers shared many similar urine microbial functions, while Bricker and CU groups exhibited opposite characteristics. Conclusion: Our study first presented urinary microbial landscapes of UD patients and demonstrated the microbiological advantage of orthotopic neobladder. Microbiota might be a potential tool for optimization of UD management.


Assuntos
Líquidos Corporais , Neoplasias da Bexiga Urinária , Derivação Urinária , Coletores de Urina , Humanos , Derivação Urinária/métodos , Cistectomia/métodos , Neoplasias da Bexiga Urinária/cirurgia
18.
Nat Neurosci ; 26(12): 2081-2089, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37996529

RESUMO

It is generally thought that under basal conditions, neurons produce ATP mainly through mitochondrial oxidative phosphorylation (OXPHOS), and glycolytic activity only predominates when neurons are activated and need to meet higher energy demands. However, it remains unknown whether there are differences in glucose metabolism between neuronal somata and axon terminals. Here, we demonstrated that neuronal somata perform higher levels of aerobic glycolysis and lower levels of OXPHOS than terminals, both during basal and activated states. We found that the glycolytic enzyme pyruvate kinase 2 (PKM2) is localized predominantly in the somata rather than in the terminals. Deletion of Pkm2 in mice results in a switch from aerobic glycolysis to OXPHOS in neuronal somata, leading to oxidative damage and progressive loss of dopaminergic neurons. Our findings update the conventional view that neurons uniformly use OXPHOS under basal conditions and highlight the important role of somatic aerobic glycolysis in maintaining antioxidant capacity.


Assuntos
Glicólise , Fosforilação Oxidativa , Animais , Camundongos , Fosfotransferases/metabolismo , Estresse Oxidativo , Glucose/metabolismo
19.
Artigo em Inglês | MEDLINE | ID: mdl-37380802

RESUMO

BACKGROUND: Advanced prostate cancer (PCa) is often resistant to immunotherapy. In this study, we examined the role of CD276 in mediating immunotherapeutic effects through changes in immune cell infiltration. METHODS: Using transcriptomic and proteomic analyses, CD276 was identified as a potential target for immunotherapy. Subsequent in vivo and in vitro experiments confirmed its role as a potential mediator of immunotherapeutic effects. RESULTS: Multi-omic analysis suggested that CD276 was identified as a key molecule regulating the immune microenvironment (IM). In vivo experiments revealed that CD276 knockdown was found to enhance CD8+ T cell infiltration into the IM. Immunohistochemical analysis of PCa samples further confirmed the same findings. CONCLUSION: CD276 was found to inhibit the enrichment of CD8+ T cells in PCa. Thus, CD276 inhibitors may be potential targets for immunotherapy.

20.
Front Surg ; 9: 1071093, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36684134

RESUMO

Purpose: This study aimed to develop a nomogram to predict the recovery of immediate urinary continence in laparoscopic radical prostatectomy (LRP) patients. Methods: A prediction model was developed based on a dataset of 154 LRP patients. Immediate urinary continence was defined as free from using pads within 7 days after the removal of the urinary catheter. The least absolute shrinkage and selection operator regression (LASSO) model was applied to screen the features. Multivariate logistic regression analysis was used to establish prediction model integrating the features selected from the LASSO regression analysis. Receiver operating curve (ROC), calibration and decision curve analysis (DCA) were used to assess the model's discrimination, calibration and clinical utility. Results: The identified features of the prediction model included age, body mass index (BMI) and three pelvic anatomic parameters measured by MRI: membranous urethral length (MUL), intravesical prostatic protrusion length (IPPL) and puborectalis muscle width (PMW). The nomogram showed good discrimination with an are under the curve(AUC) of 0.914 (95% CI, 0.865-0.959, p < 0.001). Moreover, good calibration was showed in the model. Lastly, DCA showed that the nomogram was clinically useful. Conclusion: The developed novel nomogram that can predict the possibility for post-prostatectomy patients to recover immediate urinary continence could be used as a counseling tool to explain urinary incontinence to patients after LRP.

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