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BACKGROUND: Artificial intelligence ultrasound of prostate (AIUSP)-targeted biopsy has been used for prostate cancer (PCa) diagnosis. The objective of this prospective multi-center head-to-head clinical randomized comparative trail (RCT) is to compare PCa detection rate in the TRUS-guided 12-core standard systematic biopsy (TRUS-SB) group and cognitive fused mpMRI-guided 12-core biopsy (mpMRI) group against AIUSP group. METHODS: Four hundred patients were randomized to three arms and underwent biopsies by TRUS-SB (n = 133), mpMRI (n = 134), and AIUSP (n = 133) between January 2015 and December 2017. In TRUS-SB group, a standard 12-core systematic biopsy was performed. In mpMRI group, mpMRI-suspicious lesions (PI-RADS 3-5) were targeted by 2-core biopsy followed by a 10-core systematic biopsy. Otherwise, 12-core systematic biopsy was performed. In AIUSP group, a 6-core targeted biopsy was performed. The primary endpoint was PCa detection rate. RESULTS: AIUSP detected the highest rate of PCa (66/133, 49.6%) compared to TRUS-SB (46/133, 34.6%, p = 0.036) and mpMRI (48/134, 35.8%, p = 0.052). Compared to TRUS-SB (35/133, 26.3%) and mpMRI (31/134, 23.1%) groups, clinically significant PCa (csPCa) detection rate was 32.3% (43/133) in AIUSP group. Overall biopsy core positive rate in the TRUS-SB group (11.0%, 176/1598) and in the mpMRI group (12.7%, 204/1608) was significantly lower than that in the AIUSP group (22.7%, 181/798, p < 0.001). CONCLUSIONS: AIUSP detected the highest rate of overall and significant PCa compared to TRUS-SB and mpMRI, and could be used as an alternative to systematic biopsy in the future. REGISTRATION: This trial was registered in ISRCTN (ISRCTN18033113).
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Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Masculino , Humanos , Próstata/diagnóstico por imagem , Próstata/patologia , Imageamento por Ressonância Magnética , Estudos Prospectivos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Biópsia , Biópsia Guiada por ImagemRESUMO
OBJECTIVE: To assess the feasibility and safety of three-dimensional (3D) laparoscopic nephrectomy in combination with bench surgery and autotransplantation for treating highly complex renal tumors. MATERIALS AND METHODS: The clinical data of six patients with highly complex renal cell carcinoma were collected. All patients underwent 3D laparoscopic nephrectomy in combination with bench surgery and autotransplantation by the same surgeons, two of them had previously undergone laparoscopic partial nephrectomy for contralateral renal cancer. RESULTS: The total operative time was 366 ± 65 min, the warm ischemia time (WIT) was 1.3 ± 0.4 min, and the cold ischemia time was 121 ± 26 min. While one patient received a diluted autologous blood transfusion, the intraoperative blood loss was 217 ± 194 ml. No increase in the serum creatinine (SCr) level was observed at postoperative day 30 compared with the preoperative time, and none of the patients received dialysis either during the hospital stay or to date. Although one patient underwent nephrectomy due to tumor recurrence in the transplanted kidney, the others reported no tumor recurrence or distant metastases on imaging to date. CONCLUSION: 3D laparoscopic nephrectomy, when combined with bench surgery and autotransplantation, can become a feasible option for treating highly complex renal cell carcinoma cases when expecting to preserve renal function maximally.
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Carcinoma de Células Renais , Neoplasias Renais , Laparoscopia , Humanos , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Transplante Autólogo , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Nefrectomia/métodos , Rim/fisiologia , Rim/patologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common malignant tumor of the kidney and is characterized by poor prognosis. We sought to build an immune-related prognostic signature and investigate its relationship with immunotherapy response in ccRCC. METHODS: Immune-related genes were identified by ssGSEA and WGCNA. The prognostic signature was conducted via univariate, least absolute shrinkage and selection operator, and multivariable Cox regression analyses. Kaplan-Meier analysis, PCA, t-SNE, and ROC were used to evaluate the risk model. RESULTS: A total of 119 immune-related genes associated with prognosis were screened out. Six immune-related genes (CSF1, CD5L, AIM2, TIMP3, IRF6, and HHLA2) were applied to construct a prognostic signature for KIRC. Kaplan-Meier analysis showed that patients in high-risk group had a poorer survival outcome than in low-risk group. The 1-, 3- and 5-year AUC of the prognostic signature was 0.754, 0.715, and 0.739, respectively. Univariate and multivariate Cox regression models demonstrated that the risk signature was an independent prognostic factor for KIRC survival. GSEA analysis suggested that the high-risk group was concentrated on immune-related pathways. The high-risk group with more regulatory T-cell infiltration showed a higher expression of immune negative regulation genes. The risk score had positively relationship with TIDE score and negatively with the response of immunotherapy. The IC50 values of axitinib, sunitinib, sorafenib, and temsirolimus were lower in the high-risk group. CONCLUSION: Our study defined a robust signature that may be promising for predicting clinical outcomes and immunotherapy and targeted therapy response in ccRCC patients.
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Carcinoma de Células Renais , Neoplasias Renais , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Imunoglobulinas , Imunoterapia , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/metabolismo , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , PrognósticoRESUMO
BACKGROUND: The tumor microenvironment (TME) is closely related to clear cell renal cell carcinoma (ccRCC) prognosis, and immunotherapy response. In current study, comprehensive bio-informative analysis was adopted to construct a TME-related lncRNA signature for immune checkpoint inhibitors (ICIs) and targeted drug responses in ccRCC patients. METHODS: The TME mRNAs were screened following the immune and stromal scores with the data from GSE15641, GSE29609, GSE36895, GSE46699, GSE53757, and The Cancer Genome Atlas (TCGA)-kidney renal clear cell carcinoma (KIRC). And the TME-related lncRNAs were recognized using correlation analysis. The TME-related lncRNAs prognostic model was constructed using the training dataset. Kaplan-Meier analysis, principal-component analysis, and time-dependent receiver operating characteristic were used to evaluate the risk model. The immune cell infiltration in TME was evaluated using the single-sample gene set enrichment analysis (ssGSEA), ESTIMATE, and microenvironment cell populations counter algorithm. The immunophenoscore (IPS) was used to assess the response to immunotherapy with the constructed model. RESULTS: In the current study, 364 TME-related lncRNAs were selected based on the integrated bioinformatical analysis. Six TME-related lncRNAs (LINC00460, LINC01094, AC008870.2, AC068792.1, and AC007637.1) were identified as the prognostic signature in the training dataset and subsequently verified in the testing and entire datasets. Patients in the high-risk group exhibited poor overall survival and disease-free survival than those in the low-risk group. The 1-, 3-, and 5-year areas under the curves of the prognostic signature in the entire dataset were 0.704, 0.683, and 0.750, respectively. The risk score independently predicted ccRCC survival based on univariate and multivariate Cox regression. GSEA analysis suggested that the high-risk group was concentrated on immune-related pathways. The high-risk group were characterized by high immune cell infiltration, high TMB and somatic mutation counters, high IPS-PD-1 + CTLA4 scores, and immune checkpoints expression upregulation, reflecting the higher ICIs response. The half inhibitory concentrations of sunitinib, temsirolimus, and rapamycin were low in the high-risk group. CONCLUSION: The TME-related lncRNAs signature constructed could reliably predict the prognosis and immunotherapy response and targeted ccRCC patients' therapy.
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Carcinoma de Células Renais , Neoplasias Renais , RNA Longo não Codificante , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Fatores Imunológicos , Imunoterapia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Microambiente Tumoral/genéticaRESUMO
The regulation of DJ-1 on AR signaling plays an important role in the pathogenesis of prostate cancer (PCa). DJ-1 could alter autophagy and regulate Beclin1-involved autophagy response through JNK-dependent pathway. JNK is known to mediate autophagy through Bcl2-Beclin1 complex. Therefore, this study aimed to investigate the significance of autophagy in DJ-1-modulated PCa cells. The current studies showed that DJ-1 overexpression in LNCaP decreased LC3 transformation and autophagosome formation. However, DJ-1 knockdown exerted the opposite effect. Moreover, DJ-1 silencing inhibited survival and promoted death in LNCaP, which was recovered by autophagy inhibition with 3-MA. In addition, DJ-1 overexpression inhibited the phosphorylation of JNK and Bcl2, and the dissociation of Beclin1 and Bcl2; while the effect of silencing DJ-1 was completely opposite. More important, JNK activated by anisimycin inhibited the proliferation and promoted death of DJ-1-overexpressed LNCaP while increasing LC3 transformation and LC3-puncta formation, but these results were reversed by the decrease of Beclin1 (by spautin-1). In contrast, when DJ-1 was silenced, the death of LNCaP, LC3 transformation, and LC3-puncta formation were inhibited by JNK inhibitor SP600125, which promoted cell proliferation. However, Bcl2 inhibition (by ABT737) reversed all the effects of SP600125. Our results suggested that DJ-1 in PCa cells could promote the growth of PCa through autophagy inhibition, and JNK-Bcl2-Beclin1 signaling played an important role in it. The study provided new insights into the role of DJ-1 in the development of PCa.
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Proteína Beclina-1/metabolismo , Sistema de Sinalização das MAP Quinases , Neoplasias da Próstata/metabolismo , Proteína Desglicase DJ-1/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Autofagia , Linhagem Celular Tumoral , Humanos , MasculinoRESUMO
Prostate cancer is the second highest caused by cancer-related death among males. microRNAs (miRs) have been reported to participate in carcinogenesis, yet their roles in prostate cancer are rarely studied or investigated. Therefore, the present study attempted to explore the effect of miR-137 in prostate cancer via regulating NADPH oxidase 4 (NOX4). Initially, microarray analysis was performed to obtain prostate cancer-related differentially expressed genes and miRs that regulated NOX4, followed by detecting the expression of miR-137 and NOX4 and its target relationship. Moreover, PC-3 cells were transfected with small interfering RNA (siNOX4) and miR-137 mimic for exploring the effect of miR-137 on glycolysis, cell proliferation, and apoptosis in prostate cancer by evaluating lactate production, glucose uptake, adenosine triphosphate (ATP) production, viability rate, and expression of cleaved caspases 3, 8, and 9, cytochrome c, cleaved poly ADP ribose polymerase (PARP), Bax, and Bcl-2. miR-137 was vital to prostate cancer progression via regulating NOX4. Besides, miR-137 expressed poorly while NOX4 expressed highly in prostate cancer. NOX4 was the target gene of miR-137. Additionally, overexpression of miR-137 and silencing of NOX4 were observed to decrease NOX4 and Bcl-2 protein expression, but increase cleaved caspases 3, 8, and 9, cytochrome c, cleaved-PARP, and Bax protein expression. Furthermore, miR-137 overexpression and NOX4 silencing contributed to decreased lactate production, glucose uptake, ATP production, and cell proliferation, but increased apoptosis rate. Collectively, the present study showed that miR-137 repressed glycolysis in prostate cancer through knockdown of NOX4, which might be a potential theoretical target for prostate cancer treatment.
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Regulação para Baixo , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , NADPH Oxidase 4/genética , Neoplasias da Próstata/genética , Adulto , Idoso , Apoptose/genética , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Glicólise/genética , Humanos , Masculino , Pessoa de Meia-Idade , NADPH Oxidase 4/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Interferência de RNARESUMO
BACKGROUND: Despite the overall success of radiotherapy, a significant number of patients develop radioresistance, which leads to local regional recurrence and distant metastasis. We studied whether repeated radiation treatment promotes androgen-independent survival of prostate cancer (PCa) cells and their metastatic potential. We also studied whether glucocorticoid receptor (GR) increase in radioresistant cells is associated with acquisition of these aggressive characteristics. METHODS: Radioresistant LNCaP (LNCaPR18) and C4-2 (C4-2R26) PCa sublines were developed by repeated radiation treatments of parental cells. Levels and activations of androgen receptor (AR) and GR in radioresistant PCa cells and respective parental cells were investigated in quantitative real-time polymerase chain reaction/Western blot analyses and immunofluorescence staining. Androgen-independent survival of radioresistant cells was tested in in vitro cell growth assays and the castration-resistant survival of these cell-derived tumors were investigated in mouse xenografts. RESULTS: Higher GR levels, but lower AR levels were detected in radioresistant cells than in parental cells. Radiation-induced GR upregulation was associated with increased intracellular cyclic adenosine monophosphate. As a consequence of GR activation, LNCaPR18 cells survived well in an androgen-depleted culture condition while parental cells could not. Results of in vivo mouse studies showed survival of LNCaPR18 cell-derived tumors in castrated mice while parental cell-derived tumors regressed. The growth of LNCaPR18 cell-derived tumors in castrated mice was impaired when treated with the anti-GR agent mifepristone. In experiments with C4-2/C4-2R26 cell sets, GR activation in C4-2R26 cells increased their metastatic potential. CONCLUSION: GR activation in radioresistant cells mediates androgen independence and facilitates PCa progression.
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Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/radioterapia , Tolerância a Radiação/efeitos da radiação , Radioterapia/efeitos adversos , Receptores Androgênicos/metabolismo , Receptores de Glucocorticoides/metabolismo , Androgênios/metabolismo , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Progressão da Doença , Relação Dose-Resposta à Radiação , Humanos , Masculino , Camundongos , Neoplasias da Próstata/química , Receptores Androgênicos/análise , Receptores de Glucocorticoides/análise , Regulação para Cima , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Metastasis in penile corpus cavernosum from esophageal squamous carcinoma is a rare but fatal disease, which was reported in cases without series studies. CASE PRESENTATION: An 84-year-old male smoker, who had a history of curative resection of esophageal squamous carcinoma 12 months before, presented with aggressive dysuria and penis pain for 1 month. Ultrasonic guided biopsy diagnosed metastatic squamous carcinoma from the primary in the esophagus. The accurately modulated conformal radiotherapy and non-steroidal antiinflammatory drugs achieved to alleviate the penis pain temporarily. But the disease progressed and disseminated in a short period. He died of multiple metastases and cancer cachexia in 4 months. CONCLUSIONS: Primary esophageal cancer metastasis to penile corpus cavernosum refers to short onset time of metastasis, extensive dissemination, bad response to treatment and poor prognosis. Palliative therapy to patients with the disease could achieve temporary local symptom relief, but not prolong survival time. More research is necessary to understand the underlying mechanism of esophagheal metastasis.
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Carcinoma de Células Escamosas/secundário , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Cuidados Paliativos , Neoplasias Penianas/secundário , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/uso terapêutico , Biópsia , Dor do Câncer/fisiopatologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Disuria/fisiopatologia , Evolução Fatal , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Penianas/tratamento farmacológico , Neoplasias Penianas/radioterapia , Pênis/diagnóstico por imagem , Pênis/fisiopatologia , Radioterapia , Doenças Raras , Fumantes , UltrassonografiaRESUMO
BACKGROUND: Methylation of the tumor suppressor gene H-cadherin (CDH13) has been reported in many cancers. However, the clinical effect of the CDH13 methylation status of patients with bladder cancer remains to be clarified. METHODS: A systematic literature search was performed to identify eligible studies in the PubMed, Embase, EBSCO, CKNI and Wanfang databases. The pooled odds ratio (OR) and the corresponding 95 % confidence interval (95 % CI) was calculated and summarized. RESULTS: Nine eligible studies were included in the present meta-analysis consisting of a total of 1017 bladder cancer patients and 265 non-tumor controls. A significant association was found between CDH13 methylation levels and bladder cancer (OR = 21.71, P < 0.001). The results of subgroup analyses based on sample type suggested that CDH13 methylation was significantly associated with bladder cancer risk in both the tissue and the urine (OR = 53.94, P < 0.001; OR = 7.71, P < 0.001; respectively). A subgroup analysis based on ethnic population showed that the OR value of methylated CDH13 was higher in Asians than in Caucasians (OR = 35.18, P < 0.001; OR = 8.86, P < 0.001; respectively). The relationships between CDH13 methylation and clinicopathological features were also analyzed. A significant association was not observed between CDH13 methylation status and gender (P = 0.053). Our results revealed that CDH13 methylation was significantly associated with high-grade bladder cancer, multiple bladder cancer and muscle invasive bladder cancer (OR = 2.22, P < 0.001; OR = 1.45, P = 0.032; OR = 3.42, P < 0.001; respectively). CONCLUSION: Our study indicates that CDH13 methylation may play an important role in the carcinogenesis, development and progression of bladder cancer. In addition, CDH13 methylation has the potential to be a useful biomarker for bladder cancer screening in urine samples and to be a prognostic biomarker in the clinic.
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Biomarcadores Tumorais/metabolismo , Caderinas/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Caderinas/genética , Humanos , Metilação , Regiões Promotoras GenéticasRESUMO
Clear cell renal cell carcinoma (ccRCC) represents a highly frequent renal cancer subtype. However, medium-chain acyl-CoA dehydrogenase (ACADM) encodes an important enzyme responsible for fatty acid ß-oxidation (FAO) and its association with prognosis and immunity in cancers has rarely been reported. Therefore, the present work focused on exploring ACADM's expression and role among ccRCC cases. We used multiple public databases and showed the hypo levels of ACADM protein and mRNA within ccRCC. Additionally, we found that ACADM down-regulation showed a remarkable relation to the advanced stage, high histological grade, as well as dismal prognostic outcome. As suggested by Kaplan-Meier curve analysis, cases showing low ACADM levels displayed shorter overall survival (OS) as well as disease-free survival (DFS). Moreover, according to univariate/multivariate Cox regression, ACADM-mRNA independently predicted the prognosis of ccRCC. In addition, this work conducted immunohistochemistry for validating ACADM protein expression and its prognostic role in ccRCC samples. KEGG and GO analyses revealed significantly enriched genes related to ACADM expression during fatty acid metabolism. The low-ACADM group with more regulatory T-cell infiltration showed higher expression of immune negative regulation genes and higher TIDE scores, which might contribute to poor response to immunotherapies. In conclusion, our results confirmed that downregulated ACADM predicted a poor prognosis for ccRCC and a poor response to immunotherapy. Our results provide important data for developing immunotherapy for ccRCC.
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Carcinoma de Células Renais , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais , Microambiente Tumoral , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Prognóstico , Feminino , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Idoso , Acil-CoA Desidrogenase/genética , Acil-CoA Desidrogenase/metabolismo , Estimativa de Kaplan-MeierRESUMO
Bronchogenic cysts are uncommon congenital malformations of the respiratory system. These cysts can be categorized as intrapulmonary, mediastinal, or ectopic. Ectopic bronchogenic cysts, which lack distinctive clinical and imaging features, are particularly challenging to diagnose. This study presents a 48-year-old woman having a small intestinal bronchogenic cyst. She was repeatedly misdiagnosed as having an ovarian chocolate cyst or a cystic mass of bladder origin three years ago. However, no cyst was found during the operation. Half a year prior to presenting at our hospital, the patient developed frequent urination, prompting her to seek further treatment. We eventually discovered a cyst in the small intestine. The histological evaluation of the specimen showed a bronchogenic cyst. Small intestine bronchogenic cysts are extremely rare and easily misdiagnosed. It should be considered as one of the differential diagnoses of pelvic cysts. Particularly, when intraoperative exploration of the pelvic cavity fails to detect any cysts, consideration should be given to the possibility of small intestine bronchogenic cysts.
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Renal cell carcinoma (RCC) stands among the top 10 malignant neoplasms with the highest fatality rates. It exhibits pronounced heterogeneity and robust metastatic behavior. Patients with RCC may present with solitary or multiple metastatic lesions at various anatomical sites, and their prognoses are contingent upon the site of metastasis. When deliberating the optimal therapeutic approach for a patient, thorough evaluation of significant risk factors such as the feasibility of complete resection, the presence of oligometastases, and the patient's functional and physical condition is imperative. Recognizing the nuanced differences in RCC metastasis to distinct organs proves advantageous in contemplating potential treatment modalities aimed at optimizing survival outcomes. Moreover, discerning the metastatic site holds promise for enhancing risk stratification in individuals with metastatic RCC. This review summarizes the recent data pertaining to the current status of different RCC metastatic sites and elucidates their role in informing clinical management strategies across diverse metastatic locales of RCC.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Metástase Neoplásica , PrognósticoRESUMO
Checkpoint kinase 2 (CHEK2) plays a crucial role in responding to DNA damage and is linked to diverse cancer types. However, its significance in the prediction of prognosis and impacts on the immune status of clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to identify the role of CHEK2 in prognosis and immune microenvironment of ccRCC. We analyzed transcriptome and clinicopathological data from the cancer genome atlas (TCGA) database and conducted functional enrichment analysis to explore molecular mechanisms. The relationship between CHEK2 and immune infiltration was evaluated, and drug sensitivity analysis was performed using the CellMiner database. The results showed that CHEK2 was an independent predictor of ccRCC prognosis and was closely associated with immune-related processes. Additionally, high expression of CHEK2 was linked to resistance to certain targeted drugs. These findings suggest that CHEK2 could serve as a biomarker for ccRCC, providing insights into tumor immune microenvironment alterations and immunotherapeutic response. Further investigation is needed to fully understand the potential of CHEK2 as a prognostic predictor and therapeutic target for ccRCC.
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Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Quinase do Ponto de Checagem 2/genética , Prognóstico , Neoplasias Renais/genética , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: Cuproptosis is a novel cell death mechanism, and FDX1 is a key gene associated with cuproptosis. However, it is unclear whether FDX1 has prognostic and immunotherapeutic value for clear cell renal carcinoma (ccRCC). METHODS: Data on FDX1 expression in ccRCC were extracted from various databases and validated using qRT-PCR and western blotting. Moreover, the survival prognosis, clinical features, methylation, and biological functions of FDX1 were evaluated, and the tumor immune dysfunction and exclusion (TIDE) score was used to explore the immunotherapy response to FDX1 in ccRCC. RESULTS: The expression of FDX1 in ccRCC tissues was significantly lower than that in normal tissues, as validated by qRT-PCR and western blotting of patient samples (P < 0.01). Moreover, low FDX1 expression was related to shorter survival time and high immune activation, as indicated by alterations in the tumor mutational burden and tumor microenvironment, stronger immune cell infiltration and immunosuppression point expression, and a higher TIDE score. CONCLUSIONS: FDX1 could serve as a novel and accessible biomarker for predicting survival prognosis, tumor immune landscape, and immune responses in ccRCC.
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Apoptose , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Western Blotting , Carcinoma de Células Renais/genética , Morte Celular , Neoplasias Renais/genética , Reação em Cadeia da Polimerase , Prognóstico , Microambiente Tumoral , CobreRESUMO
Solamargine (SM), an active compound derived from Solanum nigrum, triggers apoptosis and inhibits the metastatic and oxidative activities of various types of tumor cells. However, the effect of SM on human renal carcinoma cells remains unknown. In the present study, the molecular mechanisms underlying the antitumor effects of SM on ACHN and 786-O cells were elucidated. Specifically, MTT and colony formation assays were conducted to evaluate the impact of SM treatment on the proliferation of ACHN and 786-O cells, and flow cytometry was conducted to determine the influence of SM on the apoptosis rates of these cells. In addition, the expression of target proteins was determined by western blotting. The results revealed that SM not only inhibited cell viability but also promoted the apoptosis of ACHN and 786-O cells in a time- and dose-dependent manner. Moreover, treatment of ACHN and 786-O cells with SM significantly enhanced the caspase-3, caspase-8 and caspase-9 activities. Furthermore, SM downregulated the expression of phosphorylated signal transducer and activator of transcription-3 (p-STAT3) and Bcl-2 but increased the expression of cleaved caspase-3, -8, -9 and Bax. BAY2353, a p-STAT3 inhibitor, inhibited the viability of ACHN and 786-O cells, increased the expression of cleaved caspase-9 and Bax and decreased the expression of p-STAT3 and Bcl-2. Further experiments demonstrated that SM inhibited tumor growth in xenograft nude mice without causing specific toxicity to the major organs. Collectively, these findings indicated that SM not only inhibited the viability but also promoted the apoptosis of ACHN and 786-O cells, through a mechanism involving downregulation of p-STAT3 expression.
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OBJECTIVE: Renal clear cell carcinoma (ccRCC) is the most common type of renal cancer. Here we aim to explore the prognosis and immunotherapeutic value of copper death-related gene Dihydrolipoamide S-acetyltransferase (DLAT) in ccRCC. METHODS: The mRNA and protein expressions and methylation level of DLAT, as well as the relation of DLAT to survival prognosis, clinical characteristics, biological function, and immune microenvironment and responses in patients with ccRCC were evaluated using multiple databases. In addition, 75 paired ccRCC tissue samples and 3 kinds of cell lines were tested for experimental validation. RESULTS: Bioinformatics analysis of multiple databases, qRT-PCR, and western blot verified that DLAT expression in ccRCC was lower than that in paracancerous tissues. Patients with low expression of DLAT had a lower survival rate, worse clinical prognosis, stronger immune cell infiltration and expression of immunosuppressive points, and higher tumor immune dysfunction and exclusion (TIDE) scores. CONCLUSIONS: DLAT was identified as an independent prognostic factor in ccRCC and was closely related to the prognosis and immune responses of patients with ccRCC.
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Apoptose , Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , Humanos , Biomarcadores , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/terapia , Di-Hidrolipoil-Lisina-Resíduo Acetiltransferase , Imunoterapia , Neoplasias Renais/genética , Neoplasias Renais/terapia , Prognóstico , Microambiente Tumoral/genética , CobreRESUMO
Background: Despite numerous treatments available, clear cell renal cell carcinoma (ccRCC) remains a deadly and invasive cancer. Anoikis-related genes (ARGs) are essential regulators of tumor metastasis and development. However, the potential roles of ARGs in ccRCC remain unclear. Methods: Based on the TCGA-KIRC cohort and GeneCards database, we identified differentially expressed ARGs in ccRCC. Then a 4 ARGs risk model was created by Cox regression and LASSO. The Kaplan-Meier and receiver operating characteristic (ROC) curves were utilized to verify the predictive efficacy of the prognostic signature. Subsequently, the possible molecular mechanism of ARGs was investigated by functional enrichment analysis. To assess the immune infiltration, immune checkpoint genes, and immune function in various risk groups, single sample gene set enrichment (ssGSEA) algorithm was employed. Furthermore, the low-risk and high-risk groups were compared in terms of tumor mutation burden (TMB). Ultimately, we analyzed the protein expression of these four ARGs utilizing the western blot test. Results: Four genes were utilized to create a risk signature that may predict prognosis, enabling the classification of KIRC patients into groups with low or high risk. The reliability of the signature was examined utilizing survival analysis and ROC analysis. According to the multivariate Cox regression result, the risk score was a reliable independent prognostic predictor for KIRC patients. The novel risk model could differentiate between KIRC patients with various clinical outcomes and represent KIRC's specific immune status. An analysis of the correlation of TMB and risk score indicated a positive correlation between them, with high TMB being potentially linked to worse outcomes. Conclusion: Based on our findings, the prognostic signature of ARGs may be employed as an independent prognostic factor for ccRCC patients. It may introduce alternative perspectives on prognosis evaluation and serve as a prominent reference for personalized and precise therapy in KIRC.
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PURPOSE: To explore the role and mechanism of curcumin (Cur) in reducing oxidative stress damage in rats with nephrolithiasis induced by ethylene glycol (EG). METHODS: Thirty male rats were divided into normal control, model, positive (10% potassium citrate), Cur-10 (10 mg/kg curcumin) and Cur-20 (20 mg/kg curcumin) groups. RESULTS: The results of kidney tissue section stained by hematoxylin-eosin and von Kossa showed that curcumin treatment can inhibit the formation of kidney stones. The biochemical test results showed that the urea (Ur), creatinine (Cr), uric acid (UA), inorganic phosphorus and Ca2+ concentrations in urine decreased after being treated with curcumin. There were significant differences between different doses of curcumin (P < 0.05). Compared with the Cur-10 group, Cur-20 had a more significant inhibitory effect on malondialdehyde (MDA) (P < 0.05). In addition, reverse transcription polymerase chain reaction (PCR) detection and immunohistochemical results indicated that the osteopontin (OPN) in the kidney was significantly reduced after curcumin treatment. CONCLUSIONS: Curcumin could reduce the oxidative stress damage caused by EG-induced kidney stones.
Assuntos
Curcumina , Cálculos Renais , Osteopontina , Animais , Masculino , Ratos , Antioxidantes/metabolismo , Curcumina/farmacologia , Rim , Cálculos Renais/tratamento farmacológico , Cálculos Renais/prevenção & controle , Cálculos Renais/metabolismo , Estresse OxidativoRESUMO
G protein-coupled receptor 119 (GPR119) is predominantly expressed in ß cells and intestinal L cells. In this study, we investigated whether oleoylethanolamide (OEA), a GPR119 endogenous ligand, and PSN632408, a GPR119 synthetic agonist, can stimulate ß-cell replication in vitro and in vivo and improve islet graft function in diabetic mice. We found that OEA and PSN632408 significantly increased numbers of insulin(+)/5-bromo-2'-deoxyuridine (BrdU)(+) ß cells in cultured mouse islets in a dose-dependent manner. All diabetic recipient mice, given marginal syngeneic islet transplants with OEA or PSN632408 or vehicle, achieved normoglycemia at 4 weeks after transplantation. However, normoglycemia was achieved significantly faster in OEA- or PSN632408-treated diabetic mice than in vehicle-treated diabetic mice (P < 0.05). The percentage of insulin(+)/BrdU(+) ß cells in islet grafts in OEA- and PSN632408-treated mice was significantly higher than in vehicle-treated mice (P < 0.01). Our data demonstrated that OEA and PSN632408 can stimulate ß-cell replication in vitro and in vivo and improve islet graft function. Targeting GPR119 is a novel therapeutic approach to increase ß-cell mass and to improve islet graft function by stimulating ß-cell replication.