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1.
Adv Sci (Weinh) ; 11(23): e2402509, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38590132

RESUMO

Diagnosis and stratification of prostate cancer (PCa) patients using the prostate-specific antigen (PSA) test is challenging. Extracellular vesicles (EVs), as a new star of liquid biopsy, has attracted interest to complement inaccurate PSA screening and invasiveness of tissue biopsy. In this study, a panel of potential small EV (sEV) protein biomarkers is identified from PCa cell lines using label-free LC-MS/MS proteomics. These biomarkers underwent further validation with plasma and urine samples from different PCa stages through parallel reaction monitoring-based targeted proteomics, western blotting, and ELISA. Additionally, a tissue microarray containing cancerous and noncancerous tissues is screened to provide additional evidence of selected sEV proteins associated with cancer origin. Results indicate that sEV protein LAMB1 is highly expressed in human plasma of metastatic PCa patients compared with localised PCa patients and control subjects, while sEV protein Histone H4 is highly expressed in human urine of high-risk PCa patients compared to low-risk PCa patients and control subjects. These two sEV proteins demonstrate higher specificity and sensitivity than the PSA test and show promise for metastatic PCa diagnosis, progression monitoring, and risk stratification.


Assuntos
Biomarcadores Tumorais , Vesículas Extracelulares , Histonas , Neoplasias da Próstata , Proteômica , Humanos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Masculino , Proteômica/métodos , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/urina , Vesículas Extracelulares/metabolismo , Histonas/metabolismo , Medição de Risco/métodos , Pessoa de Meia-Idade , Idoso , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Laminina
2.
J Transl Med ; 22(1): 314, 2024 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532419

RESUMO

BACKGROUND: Bladder cancer (BC) is a very common urinary tract malignancy that has a high incidence and lethality. In this study, we identified BC biomarkers and described a new noninvasive detection method using serum and urine samples for the early detection of BC. METHODS: Serum and urine samples were retrospectively collected from patients with BC (n = 99) and healthy controls (HC) (n = 50), and the expression levels of 92 inflammation-related proteins were examined via the proximity extension analysis (PEA) technique. Differential protein expression was then evaluated by univariate analysis (p < 0.05). The expression of the selected potential marker was further verified in BC and adjacent tissues by immunohistochemistry (IHC) and single-cell sequencing. A model was constructed to differentiate BC from HC by LASSO regression and compared to the detection capability of FISH. RESULTS: The univariate analysis revealed significant differences in the expression levels of 40 proteins in the serum (p < 0.05) and 17 proteins in the urine (p < 0.05) between BC patients and HC. Six proteins (AREG, RET, WFDC2, FGFBP1, ESM-1, and PVRL4) were selected as potential BC biomarkers, and their expression was evaluated at the protein and transcriptome levels by IHC and single-cell sequencing, respectively. A diagnostic model (a signature) consisting of 14 protein markers (11 in serum and three in urine) was also established using LASSO regression to distinguish between BC patients and HC (area under the curve = 0.91, PPV = 0.91, sensitivity = 0.87, and specificity = 0.82). Our model showed better diagnostic efficacy than FISH, especially for early-stage, small, and low-grade BC. CONCLUSION: Using the PEA method, we identified a panel of potential protein markers in the serum and urine of BC patients. These proteins are associated with the development of BC. A total of 14 of these proteins can be used to detect early-stage, small, low-grade BC. Thus, these markers are promising for clinical translation to improve the prognosis of BC patients.


Assuntos
Detecção Precoce de Câncer , Neoplasias da Bexiga Urinária , Humanos , Estudos Retrospectivos , Curva ROC , Detecção Precoce de Câncer/métodos , Neoplasias da Bexiga Urinária/patologia , Biomarcadores Tumorais
3.
Mater Today Bio ; 25: 100947, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38298562

RESUMO

Cyclophosphamide is commonly used in the treatment of various cancers and autoimmune diseases, while concurrently imposing substantial toxicity on the bladder, frequently manifesting hemorrhagic cystitis. Intravesical interventions, such as hyaluronic acid supplementation, present a therapeutic strategy to reinstate bladder barrier function and alleviate the effects of metabolic toxicants. However, it remains a great challenge to achieve efficient cyclophosphamide-induced hemorrhagic cystitis (CHC) management with accelerated tissue repair owing to the low wet-adhesion, poor hemostasis, and acute inflammatory responses. To address these issues, a hemostatic and anti-inflammatory hydrogel adhesive of chitosan methylacryloyl/silk fibroin methylacryloyl (CHMA/SFMA) is developed for promoting the healing of CHC. The obtained hydrogels show a high adhesive strength of 26.21 N/m with porcine bladder, facilitating the rapid hemostasis within 15 s, and reinstate bladder barrier function. Moreover, this hydrogel adhesive promotes the proliferation and aggregation of SV-HUC-1 and regulates macrophage polarization. Implanting the hydrogels into CHC bladders of a SD rat model, they not only can be completely biodegraded in 14 days, but also effectively control hematuria and inflammation, and accelerate angiogenesis, thereby significantly promote the healing of bladder injury. Overall, CHMA/SFMA hydrogels exhibit rapid hemostasis for treating CHC and accelerate muscle tissue repair via angiogenesis and inflammation amelioration, which may provide a new path for managing severe hemorrhagic cystitis in the clinics.

4.
J Nanobiotechnology ; 21(1): 480, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38093355

RESUMO

Current diagnostic tools for prostate cancer (PCa) diagnosis and risk stratification are insufficient. The hidden onset and poor efficacy of traditional therapies against metastatic PCa make this disease a heavy burden in global men's health. Prostate cancer-derived extracellular vesicles (PCDEVs) have garnered attention in recent years due to their important role in communications in tumor microenvironment. Recent advancements have demonstrated PCDEVs proteins play an important role in PCa invasion, progression, metastasis, therapeutic resistance, and immune escape. In this review, we briefly discuss the applications of sEV proteins in PCa diagnosis and prognosis in liquid biopsy, focus on the roles of the PCa-derived small EVs (sEVs) proteins in tumor microenvironment associated with cancer progression, and explore the therapeutic potential of sEV proteins applied for future metastatic PCa therapy.


Assuntos
Vesículas Extracelulares , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapia , Neoplasias da Próstata/metabolismo , Prognóstico , Vesículas Extracelulares/metabolismo , Biópsia Líquida , Microambiente Tumoral
5.
BJS Open ; 7(6)2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-38155395

RESUMO

BACKGROUND: It is not clear whether the routine placement of a pelvic drain after robot-assisted radical prostatectomy is a necessity. The aim of this study was to investigate this through a meta-analysis of RCTs and non-randomized studies. METHODS: A search was performed in PubMed/MEDLINE, Embase, the Cochrane Library, and the Web of Science, up to 9 March 2023, for clinical trials comparing no drain with pelvic drain placement for patients with prostate cancer after robot-assisted radical prostatectomy. Two researchers independently conducted literature screening, data extraction, and quality assessment. A random-effect model was assumed for all analyses. The Cochrane Collaboration's risk-of-bias tool was used to evaluate the methodological quality of RCTs and, for non-randomized studies, the ROBINS-I tool was used (where ROBINS-I stands for Risk Of Bias In Non-randomized Studies - of Interventions). This meta-analysis was prospectively registered in PROSPERO, the international prospective register of systematic reviews (CRD42023406429). RESULTS: A total of six studies with 1480 patients were included in the meta-analysis. Both the meta-analysis of RCTs and the meta-analysis of non-randomized studies showed that patients without drains had a similar estimated blood loss (mean difference 40.49 ml, 95% c.i. -59.75 to 140.74 ml, P = 0.430, and mean difference -14.20 ml, 95% c.i. -32.26 to 3.87 ml, P = 0.120 respectively), overall complication rate (OR 0.60, 95% c.i. 0.35 to 1.04, P = 0.070, and OR 0.90, 95% c.i. 0.59 to 1.39, P = 0.640 respectively), Clavien-Dindo grade I-II complication rate (OR 0.62, 95% c.i. 0.34 to 1.13, P = 0.120, and OR 0.83, 95% c.i. 0.28 to 2.51, P = 0.750 respectively), Clavien-Dindo grade III-V complication rate (OR 0.60, 95% c.i. 0.10 to 3.69, P = 0.590, and OR 0.92, 95% c.i. 0.25 to 3.39, P = 0.900 respectively), and duration of hospital stay (mean difference -0.08 days, 95% c.i. -0.45 to 0.29 days, P = 0.670, and mean difference -0.64 days, 95% c.i. -2.67 to 1.39 days, P = 0.540 respectively) compared with routinely drained patients. Meta-analysis of non-randomized studies revealed that the duration of operation for patients without drains was shorter than that for patients with drains (mean difference -34.88 min, 95% c.i. -43.58 to -26.18 min, P < 0.001), but the meta-analysis of RCTs indicated that there was no significant difference between the two groups (mean difference -7.64 min, 95% c.i. -15.61 to 0.32 min, P = 0.060). CONCLUSION: The intraoperative and postoperative outcomes of patients without drains were not inferior to those of patients with drains. In selected patients, pelvic drains can be omitted after robot-assisted radical prostatectomy.


Assuntos
Drenagem , Complicações Pós-Operatórias , Prostatectomia , Procedimentos Cirúrgicos Robóticos , Humanos , Masculino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Prostatectomia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversos
6.
Front Oncol ; 13: 1175183, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37637034

RESUMO

Background: The role of Eph receptors and related ephrin (EFN) ligands (as the largest family of transmembrane-bound RTKs) in immunomodulation in many types of cancer, especially bladder cancer (BLCA), is scarcely known. Methods: A pan-cancer dataset was retrieved from The Cancer Genome Atlas (TCGA) to explore the relation between Eph receptor/EFN ligand family genes and immunomodulators and tumor-infiltrated immune cells (TIICs). Local BLCA, GSE32894, and GSE31684 cohorts were applied to validate. The IMvigor210 cohort was employed to explore the relationship between EPHB6 and immunotherapy response. Moreover, association between EPHB6 and molecular subtype was investigated to explore potential therapeutic strategies. Immunohistochemical staining of CD8 and CD68 was performed to validate the correlation between EPHB6 and TIICs. Results: The pan-cancer analysis revealed variations in the immunological effects of Eph receptor/EFN ligand family genes across different types of cancer. EPHB6 expression negatively correlated with the expression of the majority of immunomodulators (including HLA and immune checkpoints), and CD8 T cells and macrophages in both the TCGA-BLCA and validation BLCA cohorts, shaping a cold immune microenvironment with inhibited immunity. In the IMvigor210 cohort, patients with high-EPHB6 highly correlated with a non-inflamed, low PD-L1 expression immune phenotype, and correspondingly, with less responders to immunotherapy. The high-EPHB6 group, enriched with the basal subtype, presented significantly fewer TP53 and more FGFR3 genomic alterations. Finally, a novel EPHB6-related Genes signature, with reliable and robust ability in prognosis prediction, was constructed. Conclusions: This study comprehensively investigated the immunological effects of Eph receptor/EFN ligand family genes pan-cancer, and specially identified the immunosuppressive role of EPHB6 in BLCA. Furthermore, EPHB6 may predict the molecular subtype and prognosis of BLCA, and serve as a novel therapeutic target to improve the sensitivity of immunotherapy.

7.
ACS Omega ; 8(21): 18523-18529, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37273592

RESUMO

Surface-enhanced Raman scattering (SERS) is a spectral detection technology with high sensitivity and detectivity and can be used to detect the fingerprint information of the molecules with ultralow concentration. Herein, a kind of immunostructure constructed by Ag nanoparticle/porous carbon (Ag NP/PorC) films as the immunosubstrate and Ag NCs as the immunoprobes was presented for ultralow level prostate-specific antigen (PSA) detection. Experimentally, the Ag NP/PorC film was first prepared with a facile method by carbonizing the gelatin-AgNO3 film in air, and Ag NCs were synthesized by the hydrothermal method. Then, the Ag NP/PorC film was modified by PSA antibodies as the substrate, while Ag NCs were decorated by R6G and PSA antibodies for probes. The sandwiched SERS detection embodiment was constructed by the immunoreaction between the PSA and PSA antibody predecorated on the substrate and probes. Our results show that the proposed SERS-type immunoassay is highly sensitive and selective to a wide range of PSA concentrations from 10-5 to 10-12 g/mL. Thereafter, it was also implemented to detect the PSA level in human serum, and the results successfully reproduce the PSA levels as those measured by the chemiluminescence method with a recovery rate above 90%. All in all, this SERS-type immunoassay provides a promising method for the early diagnosis of prostate cancer.

8.
Cancer Med ; 12(11): 12106-12117, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37021811

RESUMO

BACKGROUND: Neoadjuvant chemotherapy followed by radical cystectomy (RC) is the standard of care for patients with muscle-invasive bladder cancer (MIBC). However, treatment outcomes are suboptimal. Camrelizumab, a PD-1 blockade, has shown benefits in several tumors. This study aimed to investigate the efficacy and safety of neoadjuvant camrelizumab in combination with gemcitabine plus cisplatin (GC) followed by RC for MIBC patients. METHODS: This was a multi-center, single-arm study that enrolled MIBC patients with a clinical stage of T2-4aN0-1M0, and scheduled for RC. Patients received three 21-day cycles of camrelizumab 200 mg on day 1, gemcitabine 1000 mg/m2 on day 1 and 8, and cisplatin 70 mg/m2 on day 2, followed by RC. The primary endpoint was pathologic complete response (pCR, pT0N0). RESULTS: From May 2020 to July 2021, 43 patients were enrolled and received study medications at nine centers in China. Three of them were deemed ineligible and excluded from efficacy analysis but included in safety analysis. In total 10 patients were unevaluable as they declined RC (two due to adverse events [AEs] and eight due to patient's willingness). Among 30 evaluable patients, 13 patients (43.3%) achieved pCR, and 16 patients (53.3%) achieved pathologic downstaging. No AEs leading to death were observed. The most common AEs were anemia (69.8%), decreased white blood cell count (65.1%), and nausea (65.1%). Immune-related AEs were all grade 1 or 2. Pathologic response was not correlated with PD-L1 expression status or tumor mutation burden. Individual genes as a biomarker for pathologic response were not identified. CONCLUSIONS: Neoadjuvant treatment with camrelizumab and GC regimen demonstrated preliminary anti-tumor activity for MIBC patients with manageable safety profiles. The study met its primary endpoint, and the following randomized trial is ongoing.


Assuntos
Cisplatino , Neoplasias da Bexiga Urinária , Humanos , Cisplatino/uso terapêutico , Gencitabina , Terapia Neoadjuvante/efeitos adversos , Neoplasias da Bexiga Urinária/patologia , Desoxicitidina/uso terapêutico , Cistectomia , Músculos/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Invasividade Neoplásica
9.
Exp Ther Med ; 25(1): 31, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36569436

RESUMO

The present single-center retrospective clinical real-world study aimed to assess the feasibility and outcomes of patients who underwent simultaneous prostate biopsy and general urological surgeries. The medical records of 49 patients who underwent prostate biopsy and general urological surgeries simultaneously from October 2016 to June 2019 were retrospectively reviewed. Patients' outcomes were evaluated 3 days, 1 month and 6 months after biopsy. Of the 49 biopsy cases, 41 were treated by transurethral prostatectomy, two by ureteroscopic lithotripsy, two by laparoscopic renal cyst decortication, two by cystostomy and two by ureteral stent extraction. The overall detection rate of clinically significant prostate cancer was 22.4%. The rate in patients with a prostate imaging reporting and data system (PI-RADS) score of 4-5 was 100%, while in cases with a PI-RADS score of <3 it was 7.1%. Postoperative complications within 3 days included hematuria in 39 (79.6%) cases, fever in three (6.1%) cases and hematochezia in two (4.1%) cases. There was no significant difference in the incidence of hematuria between the transrectal and transperineal approaches; however, the overall incidence of complications was significantly reduced after switching from a transrectal approach to a transperineal approach. No complications were observed after 1 or 6 months. In summary, combining simultaneous prostate biopsy to general urological surgeries is a safe and feasible approach. The transperineal approach has a lower incidence of complications. This method may benefit certain patients who are concurrently undergoing general urological surgeries and are under suspicion of prostate cancer in real-world clinical practice.

10.
Front Oncol ; 12: 957892, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35965573

RESUMO

Background: This study aimed to analyze the pathological characteristics and predictive factors of prostate biopsy in men with PSA levels below 4.0 ng/ml. Patients and methods: We retrospectively analyzed 158 patients who underwent prostate biopsy with PSA levels below 4.0 ng/ml. Pathological results were statistically analyzed. The logistic regression analysis was used to determine the predictive factors for malignant outcomes. Subgroup analysis was performed on patients who received surgery and the postoperative pathological upgrading was counted. Results: A total of 143 patients were enrolled. The tumor detection rate was 20.3%. Among these patients, most of them (79.3%) had prostate adenocarcinoma, but rare malignant tumors also accounted for 20.7%. Logistic regression analysis indicated that the only independent predictive factor for a positive prostate biopsy was the PI-RADS score. For prostate adenocarcinoma cases, 95.7% of them were organ localized and 47.8% of cases were clinically significant. Subgroup analysis was performed on 14 patients who received surgical treatment. 28.6% of patients were upgraded to clinically significant prostate cancer, while 64.3% of patients had an upgrade in tumor stage. Conclusion: Our study indicated that 20.3% of men with PSA levels between 0 and 4.0 ng/ml were diagnosed with prostate malignancies. Among these patients, most of them (79.3%) were diagnosed with prostate adenocarcinoma, and several uncommon types of malignancies were also detected in 20.7% of patients. The only risk factor for a positive biopsy in patients with a low PSA concentration was the PI-RADS score. It should be emphasized that the invasiveness of PCa patients diagnosed by biopsy may be underestimated as more than half of patients will upgrade their Gleason score or clinical stages after surgery. Thus, clinicians should pay more attention to patients with PSA levels between 0 and 4.0 ng/ml.

11.
Mater Today Bio ; 16: 100388, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35967737

RESUMO

Urologic diseases are commonly diagnosed health problems affecting people around the world. More than 26 million people suffer from urologic diseases and the annual expenditure was more than 11 billion US dollars. The urologic cancers, like bladder cancer, prostate cancer and kidney cancer are always the leading causes of death worldwide, which account for approximately 22% and 10% of the new cancer cases and death, respectively. Organ transplantation is one of the major clinical treatments for urological diseases like end-stage renal disease and urethral stricture, albeit strongly limited by the availability of matching donor organs. Tissue engineering has been recognized as a highly promising strategy to solve the problems of organ donor shortage by the fabrication of artificial organs/tissue. This includes the prospective technology of three-dimensional (3D) bioprinting, which has been adapted to various cell types and biomaterials to replicate the heterogeneity of urological organs for the investigation of organ transplantation and disease progression. This review discusses various types of 3D bioprinting methodologies and commonly used biomaterials for urological diseases. The literature shows that advances in this field toward the development of functional urological organs or disease models have progressively increased. Although numerous challenges still need to be tackled, like the technical difficulties of replicating the heterogeneity of urologic organs and the limited biomaterial choices to recapitulate the complicated extracellular matrix components, it has been proved by numerous studies that 3D bioprinting has the potential to fabricate functional urological organs for clinical transplantation and in vitro disease models.

12.
World J Clin Cases ; 9(28): 8453-8460, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34754853

RESUMO

BACKGROUND: Granular cell tumor (GCT) is a neurogenic tumor mainly occurring in the head and neck. GCT in the genitourinary system is extremely rare and only sporadic cases of urinary bladder GCT have been reported. Most urinary bladder GCT cases are benign and only two malignant cases have been reported. Due to its rarity, no consensus criteria for the treatment of urinary bladder GCT are available at present. CASE SUMMARY: A 62-year-old Chinese woman was found to have a urinary bladder tumor without any clinical manifestations on physical examination. Cystoscopy revealed a semispherical shaped lesion measuring approximately 4.0 cm in diameter at the junction of the left wall and roof of the bladder, which was covered with normal bladder mucosa. Computed tomography scan demonstrated a high-density lesion on the left wall of the bladder, measuring approximately 2.9 cm × 2.4 cm with clear boundaries. Contrast-enhanced pelvic magnetic resonance imaging revealed a space-occupying lesion on the left wall of the bladder (non-mucosal origin/ external pressure), which was preliminarily suspected to be a desmoplastic fibroma or leiomyoma. In the context of the above findings, a pre-operative diagnosis of bladder leiomyoma was made. The patient consequently underwent a laparoscopic partial cystectomy. The resected bladder mass looked yellowish and well-demarcated, measuring 4.0 cm × 3.5 cm and infiltrated the muscular layer. The diagnosis of urinary bladder GCT was finally made by postoperative pathology, with positive immunohistochemical S-100 staining and negative pancytokeratin. The patient has been followed for 6 mo so far, with no tumor recurrence detected. CONCLUSION: This case highlights the biological feature and differential diagnosis of urinary bladder GCT at the pathological and molecular levels. Transurethral resection of the bladder tumor and partial cystectomy are recommended in most urinary bladder GCT cases, while radical cystectomy is recommended in malignant cases.

13.
Front Oncol ; 11: 740868, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34589437

RESUMO

PURPOSE: The purpose of this study is to explore the value of combining bpMRI and clinical indicators in the diagnosis of clinically significant prostate cancer (csPCa), and developing a prediction model and Nomogram to guide clinical decision-making. METHODS: We retrospectively analyzed 530 patients who underwent prostate biopsy due to elevated serum prostate specific antigen (PSA) levels and/or suspicious digital rectal examination (DRE). Enrolled patients were randomly assigned to the training group (n = 371, 70%) and validation group (n = 159, 30%). All patients underwent prostate bpMRI examination, and T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) sequences were collected before biopsy and were scored, which were respectively named T2WI score and DWI score according to Prostate Imaging Reporting and Data System version 2 (PI-RADS v.2) scoring protocol, and then PI-RADS scoring was performed. We defined a new bpMRI-based parameter named Total score (Total score = T2WI score + DWI score). PI-RADS score and Total score were separately included in the multivariate analysis of the training group to determine independent predictors for csPCa and establish prediction models. Then, prediction models and clinical indicators were compared by analyzing the area under the curve (AUC) and decision curves. A Nomogram for predicting csPCa was established using data from the training group. RESULTS: In the training group, 160 (43.1%) patients had prostate cancer (PCa), including 128 (34.5%) with csPCa. Multivariate regression analysis showed that the PI-RADS score, Total score, f/tPSA, and PSA density (PSAD) were independent predictors of csPCa. The prediction model that was defined by Total score, f/tPSA, and PSAD had the highest discriminatory power of csPCa (AUC = 0.931), and the diagnostic sensitivity and specificity were 85.1% and 87.5%, respectively. Decision curve analysis (DCA) showed that the prediction model achieved an optimal overall net benefit in both the training group and the validation group. In addition, the Nomogram predicted csPCa revealed good estimation when compared with clinical indicators. CONCLUSION: The prediction model and Nomogram based on bpMRI and clinical indicators exhibit a satisfactory predictive value and improved risk stratification for csPCa, which could be used for clinical biopsy decision-making.

14.
BMC Urol ; 21(1): 109, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34399738

RESUMO

BACKGROUND:  Hunner's interstitial cystitis (HIC) is a complex disorder characterized by pelvic pain, disrupted urine storage, and Hunner lesions seen on cystoscopy. There are few effective diagnostic biomarkers. In the present study, we used the novel machine learning tool CIBERSORT to measure immune cell subset infiltration and potential novel diagnostic biomarkers for HIC. METHODS: The GSE11783 and GSE57560 datasets were downloaded from the Gene Expression Omnibus for analysis. Ten HIC and six healthy samples from GSE11783 were analyzed using the CIBERSORT algorithm. Gene Set Enrichment Analysis (GSEA) was performed to identify biological processes that occur during HIC pathogenesis. Finally, expression levels of 11 T cell follicular helper cell (Tfh) markers were compared between three healthy individuals and four patients from GSE57560. RESULTS: Six types of immune cells in HIC from GSE11783 showed significant differences, including resting mast cells, CD4+ memory-activated T cells (CD3+ CD4+ HLA-DR+ cells), M0 and M2 macrophages, Tfh cells, and activated natural killer cells. Except for plasma cells, there were no significant differences between Hunner's lesion and non-Hunner's lesion areas in HIC. The GSEA revealed significantly altered biological processes, including antigen-antibody reactions, autoimmune diseases, and infections of viruses, bacteria, and parasites. There were 11 Tfh cell markers with elevated expression in patients from GSE57560. CONCLUSION: This was the first demonstration of Tfh cells and CD3+ CD4+ HLA-DR+ cells with elevated expression in HIC. These cells might serve as novel diagnostic biomarkers.


Assuntos
Cistite Intersticial/diagnóstico , Cistite Intersticial/imunologia , Aprendizado de Máquina , Células T Auxiliares Foliculares/imunologia , Biomarcadores/metabolismo , Complexo CD3/imunologia , Antígenos CD4/imunologia , Antígenos HLA-DR/imunologia , Humanos , Células Matadoras Naturais/imunologia , Mastócitos/imunologia , Células B de Memória/imunologia , Células T de Memória/imunologia , Plasmócitos/imunologia
15.
Front Oncol ; 11: 643413, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34109111

RESUMO

We report on a case of metastatic urothelial bladder carcinoma (mUBC) treated with anlotinib combined with sintilimab. A 69-year-old male was diagnosed with non-muscle invasive bladder cancer (NMIBC). He received transurethral resection of bladder tumor (TURBT) and intravesical gemcitabine chemotherapy. After the patients' cancer progressed to mUBC, cisplatin-based chemotherapy (gemcitabine combined with cisplatin, GC) was performed to this patient as first line therapy for four cycles. However, the disease progressed again within 6 months. Local radiotherapy was performed on the metastatic lesions, and after radiotherapy, the patient received anti-PD-1 antibody (sintilimab 200 mg, q3w)combined with Albumin-bound (Nab)-paclitaxel (100 mg, qw) as the second-line therapy, but the patient's cancer was still observed to be progressing. Molecular characterization confirmed the presence of FGFR3 mutations in the patient. Anlotinib was recommended to this patient. After the patient was fully informed and he was aware of off-label use of the drug, then, Nab-paclitaxel was replaced by anlotinib (10 mg D1-14, q3w) and sintilimab infusions were maintained for every 3 weeks. Partial response (PR) was observed through imaging examinations and stable disease (SD) was observed for more than 11 months; the patient's quality of life also improved. This case suggested that anlotinib combined with sintilimab may be a safe and effective choice in the treatment of mUBC in patients with FGFR3 mutations.

16.
Am J Cancer Res ; 11(4): 1286-1303, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33948358

RESUMO

Pinin (PNN), a desmosome associated protein, was demonstrated to be over-expressed and act as a tumor-promoting factor in ovarian cancer, hepatocellular carcinoma and colorectal cancer. However, the precise role of PNN in prostate cancer is still unknown. In the study, we reported that PNN was upregulated in prostate cancer tissues and PNN expression was positively associated with Gleason score, tumor stage and tumor metastasis. PNN promoted cell growth and tumorigenicity in vitro and in vivo, and modulated cell growth through driving G1/S transition via CDK6, CDK2, and Cyclin D1 in prostate cancer cells. Furthermore, PNN accelerated cell invasion, migration and EMT processes of prostate cancer cells, accompanied with the up-regulation of MMP-2, MMP-9, N-cadherin, Vimentin and down-regulation of E-cadherin. Mechanism study demonstrated that the proliferation- and motility-promoting effects of PNN on prostate cancer cells dependent on the activation of CREB, which was reversed by CREB inhibition. More important, PNN activated CREB via PI3K/AKT and ERK/MAPK pathway. Collectively, these findings indicated that PNN plays important roles in prostate cancer tumorigenesis and progression and it is a potential therapeutic target for prostate cancer treatment.

17.
Onco Targets Ther ; 14: 2797-2803, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33907422

RESUMO

Prostate cancer (PCa) is one of the most common types of malignancy, most patients with PCa will eventually progress to metastatic castration-resistant prostate cancer (mCRPC), which has a poor prognosis. Since 2004, chemotherapy has been approved by the FDA as the first-line treatment for mCRPC, and docetaxel-based regimens have been shown to improve both the patients' symptoms and overall survival (OS). 10 cycles of docetaxel therapy are usually given to patients with mCPRC, but there is still no consensus on the optimal number of treatment cycles. Here, we present three cases of mCRPC patients that received maintenance long-term multiple-cycles docetaxel treatment. We believe that this new treatment strategy may benefit carefully selected mCRPC patients and provide several key advantages such as maximum exposure to drugs, improvements in drug efficacy, and reduce the risk of developing drug resistance.

18.
Int Urol Nephrol ; 53(6): 1239-1245, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33515155

RESUMO

PURPOSE: Blind insertion limits the application of percutaneous peritoneal dialysis (PD) catheter placement. In this study, we first described the use of an optical puncture system in the PD catheter insertion, and investigated the feasibility and advantages of this modified technique. METHODS: This retrospective study included 65 patients with chronic kidney disease stage 5 (CKD5) who received ultrasound-guided percutaneous PD catheter insertion with or without optical puncture system assistance between June 2018 and July 2019. The patients' characteristics as well as the surgical outcomes and complications were compared between the modified group and the routine percutaneous insertion group. RESULTS: Twenty-five patients underwent optical puncture system assistant insertion, whereas 40 patients received routine percutaneous insertion. More patients had previous abdominal surgical histories in the modified group than those in the routine group (24.0% vs. 5.0%, p = 0.047). The time of accessing to the abdominal cavity was significantly shorter in the modified group (median [IQR]; 1.1 min [0.8-1.3] vs. 5.0 min [4.0-6.0]; p < 0.001). Meanwhile, the time of the whole procedure was also significantly shorter in the modified group (median [IQR]; 26.0 min [25.0-29.0] vs. 33.0 min [29.0-35.0]; p < 0.001). None of the patient in the modified group, while two patients (5.0%) in the routine group converted to open procedure. There were no significant differences in the short and long postoperative complications between the two groups. CONCLUSIONS: The operation of ultrasound-guided PD catheter placement with the optical puncture system is easy, safe, fast and accurate, whereby the PD catheter can be implanted percutaneously and visually under local anesthesia with minimal procedure-related complications. The visible puncture of the optical puncture system may facilitate ultrasound-guided percutaneous PD catheter insertion in patients with obesity and previous abdominal surgeries.


Assuntos
Cateterismo/métodos , Cateteres de Demora , Diálise Peritoneal/instrumentação , Punções/métodos , Adulto , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Cirurgia Assistida por Computador
19.
Ann Palliat Med ; 10(2): 1438-1444, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33081478

RESUMO

BACKGROUND: Prostate cancer is the most common type of malignancy in elderly men. Although elderly patients are commonly encountered in clinical practice, few studies have focused on the value of chemotherapy in elderly patients. In this study, we reviewed the use of docetaxel with prednisolone in elderly men (aged ≥80 years) with metastatic castration-resistant prostate cancer (mCRPC) at Ningbo First Hospital with a focus on efficacy and toxicity. METHODS: A retrospective study including a series of men aged ≥80 years with mCRPC and received docetaxel plus prednisone chemotherapy between August 2011 and May 2019. All these cases were selected from the Ningbo First Hospital prostate cancer database located in Zhejiang Province, China. RESULTS: Sixteen patients were identified, with a mean age of 82 years (range, 80 to 87 years). All patients have received a median of four and half cycles (range, 1-10) of 3-week (60-75 mg/m2 ) docetaxel regimens and 5 mg prednisone twice per day. Seven (43.75%) patients completed more than six cycles. Ten (62.50%) patients had a good prostate-specific antigen (PSA) response of ≥50% decline. Eight (50.00%) patients had ostealgia before receiving docetaxel treatment and six of them (75.00%) experienced reduced pain after the treatment. Hematologic toxicity was observed in six (37.50%) patients with neutropenia, one of which was diagnosed with agranulocytosis and had to be admitted for the same reason. Other adverse reactions such as fever, debilitation, and alopecia were also observed. CONCLUSIONS: Very elderly patients (aged ≥80 years) with mCRPC are easy to be neglected and infrequently involved in clinical trials. Our study demonstrates that docetaxel chemotherapy plus prednisone is tolerable and effective among Chinese elderly patients (≥80 years) with mCRPC. Docetaxel chemotherapy may be given under careful surveillance even in frail elderly patients.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , China , Docetaxel/efeitos adversos , Humanos , Masculino , Prednisolona/efeitos adversos , Prednisona/efeitos adversos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento
20.
Front Oncol ; 10: 1720, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32984054

RESUMO

BACKGROUND: The receptor-interacting protein kinase 3 (RIP3/RIPK3) was recently found to be a critical regulator of programmed necrosis/necroptosis. However, the biological role and clinical significance of RIP3 in prostate cancer remain obscure. METHODS: Western blotting and QRT-PCR were performed to detect the level of RIP3 in prostate cancer cells. Fixed cancer tissue and normal tissue specimens were subjected to immunohistochemical analysis of RIP3. Cell migration and invasion abilities were evaluated by transwell assays. In vitro proliferative ability was examed by MTS. And in vivo nude mice model were used to evaluate the effect of RIP3 ectopic expression on proliferative capability. Cell cycle of prostate cancer cells were analyzed by flow cytometry. Changes in some related proteins caused by RIP3 overexpression were explored using Western blotting. RESULTS: RIP3 was significantly down-regulated in prostate cancer cell lines and clinical prostate tumor samples. And over-expressing RIP3 suppressed the migration and invasion of prostate cancer cells. Two important matrix metalloproteinases MMP2, MMP9 which enables the destruction of the histological barrier of tumor cell invasion and three mesenchymal markers Vimentin, fibronectin, and N-cadherin were under-expressed due to the overexpression of RIP3, but the E-cadherin level which is the epithelial marker was increased. Furthermore, our results also showed that RIP3 can inhibit the proliferation and tumorigenicity of prostate cancer cells both in vitro and in vivo by phosphorylating MLKL, which were reversed by MLKL inhibitor treatment, indicating that necroptosis was involved in cell death. CONCLUSION: Taken together, these findings indicated that RIP3 is responsible for the progression of prostate cancer, suggesting that RIP3 might have the potential to be a prognostic marker or a therapeutic target against prostate cancer.

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