RESUMO
Kidney renal clear cell carcinoma (KIRC) is a highly immune-infiltrated kidney cancer with the highest mortality rate and the greatest potential for invasion and metastasis. Solute carrier family 11 member1 (SLC11A1) is a phagosomal membrane protein located in monocytes and plays a role in innate immunity, autoimmune diseases, and infection, but its expression and biological role in KIRC is still unknown. In this study, we sought to investigate the potential value of SLC11A1 according to tumor growth and immune response in KIRC. TIMER and UALCAN database was used to analyze the expression feature and prognostic significance of SLC11A1 and its correlation with immune-related biomarkers in KIRC. Proliferation, migration, and invasion were measured using colony formation, EdU, and transwell assays. Role of SLC11A1 on KIRC tumor growth was examined by the xenograft tumor model in vivo. Effects of KIRC cells on macrophage polarization and the proliferation and apoptosis of CD8+ T cells were analyzed using flow cytometry assays. Herein, SLC11A1 was highly expressed in KIRC tissues and cell lines. SLC11A1 downregulation repressed KIRC cell proliferation, migration, invasion, macrophage, and lymphocyte immunity in vitro, as well as hindered tumor growth in vivo. SLC11A1 is significantly correlated with immune cell infiltration and immune-related biomarkers. In KIRC patients, SLC11A1 is highly expressed and positively correlated with the immune-related factors CCL2 and PD-L1. SLC11A1 induced CCL2 and PD-L1 expression, thereby activating the JAK/STAT3 pathway. SLC11A1 deficiency constrained KIRC cell malignant phenotypes and immune response via regulating CCL2 and PD-L1-mediated JAK/STAT3 pathway, providing a promising therapeutic target for KIRC treatment.
Assuntos
Carcinoma de Células Renais , Proteínas de Transporte de Cátions , Proliferação de Células , Neoplasias Renais , Microambiente Tumoral , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/metabolismo , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/imunologia , Neoplasias Renais/genética , Animais , Linhagem Celular Tumoral , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Camundongos , Movimento Celular , Progressão da Doença , Camundongos Nus , Linfócitos T CD8-Positivos/imunologia , Apoptose , Feminino , Quimiocina CCL2/metabolismo , Quimiocina CCL2/genética , Masculino , Transdução de Sinais , Invasividade Neoplásica , Regulação Neoplásica da Expressão Gênica , Camundongos Endogâmicos BALB CRESUMO
BACKGROUND: Renal cell carcinoma (RCC) is a type of cancer that can develop at any point in adulthood, spanning the range of age-related changes that occur in the body. However, the specific molecular mechanisms underlying the connections between age and genetic mutations in RCC have not been extensively investigated. METHODS: Clinical and genetic data from patients diagnosed with RCC were collected from two prominent medical centers in China as well as the TCGA dataset. The patients were categorized into two groups based on their prognosticated age: young adults (YAs) and older adults (OAs). Univariate and multivariate analysis were employed to evaluate the relationships between age and genetic mutations. Furthermore, a mediation analysis was conducted to assess the association between age and overall survival, with genetic disparities serving as a mediator. RESULTS: Our analysis revealed significant differences in clinical presentation between YAs and OAs with RCC, including histopathological types, histopathological tumor stage, and sarcomatoid differentiation. YAs were found to have lower mutation burden and significantly mutated genes (SMGs) of RCC. However, we did not observe any significant differences between the two groups in terms of 10 canonical oncogenic signaling pathways-related genes mutation, telomerase-related genes (TRGs) mutation, copy number changes, and genetic mutations associated with clinically actionable targeted drugs. Importantly, we demonstrate superior survival outcomes in YAs, and we confirmed the mediating effect of genetic disparities on these survival outcome differences between YAs and OAs. CONCLUSION: Our findings reveal previously unrecognized associations between age and the molecular underpinnings of RCC. These associations may serve as valuable insights to guide precision diagnostics and treatments for RCC.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Mutação , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/mortalidade , Masculino , Feminino , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Adulto , Pessoa de Meia-Idade , Idoso , Fatores Etários , Prognóstico , China/epidemiologia , Adulto Jovem , Genômica/métodos , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) has been confirmed to play oncogenic role in many cancers. However, the role and mechanism of IGF2BP2 in bladder cancer (BCa) still deserves to be further revealed. METHODS: The mRNA and protein levels of IGF2BP2 and neuronilin-1 (NRP1) were detected by real-time quantitative PCR (RT-qPCR) and western blot. Cell proliferation, apoptosis, migration and invasion were determined using colony formation assay, EdU assay, CCK8 assay, flow cytometry and transwell assay. Xenograft tumor model was conducted to evaluate the role of IGF2BP2 in vivo. THP-1-M0 macrophages were co-cultured with the condition medium (CM) of BCa cells to induce polarization. M2 macrophage polarization was assessed by detecting the mRNA levels of M2 macrophage markers using RT-qPCR and measuring the proportion of M2 macrophage markers using flow cytometry. Moreover, MeRIP and RIP assay were performed to assess m6A level and the interaction between IGF2BP2 and NRP1. RESULTS: IGF2BP2 and NRP1 were upregulated in BCa tissues and cells. IGF2BP2 knockdown suppressed BCa cell growth and metastasis, as well as inhibited BCa tumor growth. After THP-1-M0 macrophages were co-cultured with the CM of BCa cells, the levels of M2 macrophage markers were markedly enhanced, while this effect was abolished by IGF2BP2 knockdown. IGF2BP2 level was positively correlated with NRP1 level, and it could increase NRP1 mRNA stability. NRP1 overexpression reversed the suppressive effect of IGF2BP2 knockdown on M2 macrophage polarization and BCa cell progression. CONCLUSION: m6A-reader IGF2BP2 enhanced M2 macrophage polarization and BCa cell progression by promoting NRP1 mRNA stability.
Assuntos
Macrófagos , Neuropilina-1 , RNA Mensageiro , Proteínas de Ligação a RNA , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/metabolismo , Humanos , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Macrófagos/metabolismo , RNA Mensageiro/metabolismo , Neuropilina-1/genética , Neuropilina-1/metabolismo , Camundongos , Regulação Neoplásica da Expressão Gênica , Animais , Polaridade Celular/fisiologia , Linhagem Celular TumoralRESUMO
OBJECTIVE: To investigate the clinical effect and safety of transurethral 1470 nm semiconductor laser vaporization and cutting in the treatment of super high age and high risk benign prostatic hyperplasia. METHODS: The clinical data of 38 patients with super-high-risk prostate who underwent transurethral surgery in our hospital from April 2016 to December 2017 were retrospectively analyzed. All patients had obvious progressive dysuria. The diagnosis of benign prostatic hyperplasia was confirmed by urinary color Doppler ultrasound, anal finger examination, PSA, prostate biopsy, etc., and prostate cancer was excluded. Each patient was aged ≥85 years old and combined with one or more types. Senile basic diseases such as diabetes, hypertension, coronary heart disease, emphysema, sequelae of cerebral infarction, etc. The patients were randomly divided into two groups. The observation group was treated with transurethral 1470 nm semiconductor laser vaporization and the control group was treated with transurethral plasma electrotomy. To observe the changes of vital signs, bleeding, duration of surgery, postoperative bladder irrigation time, urinary catheter retention time, and changes of hemoglobin before and after surgery. Surgical safety. The international prostate symptom score (IPSS), quality of life score (QoL), maximum urinary flow rate (Qmax), and post-void residual urine volume (PVR) were evaluated 2 months after surgery and compared with preoperative evaluation to evaluate the surgical outcome. RESULTS: All 38 operations were successfully completed.The vital signs of the patients were stable during the operation. The average operation time of the observation group and the control group was (79.6±24.7 vs 69.5±19.8) min, P>0.05. The hemoglobin decreased by (6.9±3.0) g/L vs (13.2±4.0) g/Lï¼ after operation.P<0.05; postoperative bladder irrigation time (14.7±2.8 vs 23.5±5.3)h, P<0.05; average postoperative urinary catheter retention time (3.8±0.4 vs 5.7±0.9)d, P<0.05; average postoperative hospital stay (5.3±1.1 vs 7.2±1.9)d, P<0.05; all patients were followed up for 2 months, IPSS, QoL, Qmax, PVR and other indicators were significantly improved compared with preoperative, no major bleeding, urinary incontinence, cardiopulmonary failure and Significant urinary tract irritation symptoms occur. CONCLUSION: Compared with plasma electric resection, transurethral 1470 nm semiconductor laser treatment of benign prostatic hyperplasia has the advantages of high safety and remarkable effect, especially suitable for patients with high age and high risk.
Assuntos
Terapia a Laser , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Retenção Urinária , Masculino , Humanos , Idoso de 80 Anos ou mais , Hiperplasia Prostática/cirurgia , Hiperplasia Prostática/patologia , Qualidade de Vida , Lasers Semicondutores/uso terapêutico , Estudos Retrospectivos , Complicações Pós-Operatórias/cirurgia , Hemoglobinas , Resultado do TratamentoRESUMO
OBJECTIVE: To explore the safety and effectiveness of the "scarless" circumcision technique (a modified sleeve-style circumcision method) that preserves the original appearance, providing a more suitable surgical option for patients with redundant prepuce. METHODS: Clinical data of patients who underwent "scarless" circumcision at the Eastern Theater Command General Hospital from April 2022 to March 2023 were collected, with patients who underwent conventional circumcision (single-use stapler method) during the same period serving as the control group. The two groups were compared in terms of operation time, postoperative recovery time, incidence of postoperative complications, and patient satisfaction rates after surgery. RESULTS: The operation time for the study group was significantly longer than that of the control group; there was no significant difference in pain scores on the day of surgery between the two groups, but the pain scores on postoperative days 1, 3, and 7 were lower in the study group than in the control group; the postoperative recovery time was significantly shorter in the study group than in the control group; regarding postoperative complications: the control group had higher rates of edema, incision infection, and wound dehiscence than the study group. A satisfaction survey conducted 30 days postoperatively showed higher satisfaction in the study group than in the control group. CONCLUSION: The "scarless" circumcision technique that preserves the original appearance is safe and effective for patients with simple redundant prepuce and is a new surgical method with value for widespread adoption.
Assuntos
Circuncisão Masculina , Masculino , Humanos , Duração da Cirurgia , Satisfação do Paciente , Período Pós-Operatório , DorRESUMO
BACKGROUND: Tumorigenic phenotype of M2 tumor-associated macrophages promote tumor progression in response to exosomes cues imposed by tumor cells. However, the effect and underlying mechanisms of clear cell renal cell carcinoma (ccRCC)-derived exosomes (ccRCC-exo) on instructing macrophages phenotype remains unclear. METHODS: Macrophages were cocultured with ccRCC-exo and then evaluate the polarization of macrophages and migration of ccRCC cells. The effect and mechanism of lncRNA AP000439.2 overexpressed or deleted exosomes on macrophages M2 polarization were examined. Xenograft tumor mice model was used for in vivo validation. RESULTS: The ccRCC-exo significantly activated macrophages to M2 phenotype presented by increased expression of transforming growth factor-beta (TGF-ß) and interleukin 10 (IL-10) at mRNA and protein levels, and these M2 macrophages in turn facilitating the migration of ccRCC cells. LncRNA AP000439.2 was highly enriched in the ccRCC-exo. Overexpression of exosomal AP000439.2 promoted M2 macrophage polarization whereas AP000439.2-deficient exosome had the opposite effects. Nuclear-localized AP000439.2 directly interacted with signal transducer and activator of transcription 3 (STAT3) proteins and phosphorylated STAT3 in macrophages. RNA-Seq results showed overexpression of AP000439.2 activated NF-κB signaling pathway. Silencing of STAT3 suppressed overexpression of AP000439.2-induced up-regulation of TGF-ß and IL-10 expression, and p65 phosphorylation. AP000439.2-deleted exosome inhibited tumor growth in vivo. CONCLUSION: Exosomes from ccRCC deliver AP000439.2 to promote M2 macrophage polarization via STAT3, thus enhancing ccRCC progression, indicating exosomal AP000439.2 might be a novel therapeutic target in ccRCC. Video Abstract.
Assuntos
Carcinoma de Células Renais , Exossomos , Neoplasias Renais , MicroRNAs , RNA Longo não Codificante , Animais , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Exossomos/metabolismo , Humanos , Interleucina-10/metabolismo , Neoplasias Renais/metabolismo , Ativação de Macrófagos/genética , Macrófagos/metabolismo , Camundongos , MicroRNAs/genética , NF-kappa B/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fatores de Crescimento Transformadores/metabolismoRESUMO
OBJECTIVE: To investigate the long-term effect of finasteride (FS) on high-risk BPH patients after treated by implantation of thermo-expandable spiral prostatic stent (TESPS). METHODS: We retrospectively analyzed the clinical data on 63 cases of BPH treated by implantation of TESPS in our Department of Urology from January 2017 to January 2019. All the patients received oral FS after operation except two cases of stent removal because of infection, 37 for more than 12 months (the long-term FS group) and the other 24 for less than 12 months (the control group). We followed up the patients at 3, 6, 12, 24, 36 and 48 months postoperatively, recorded the incidence of hematuria and infection, IPSS, maximum urinary flow rate (Qmax) and residual urine volume (PVR), and compared them between the two groups of patients. RESULTS: At 48 months after operation, the incidence rates of postoperative hematuria and infection were significantly lower in the long-term FS group than in the control (P < 0.05), but evidently increasing with the prolonging of medication time. The total effectiveness rate was as high as 95.1% at 3 months, but only 63.6% at 48 months, significantly higher, however, in the long-term FS than in the control group (69.2% vs 55.6%, P < 0.05), and the IPSS, Qmax and PVR were also remarkably higher in the former than in the latter group (P < 0.05). CONCLUSION: The long-term effect of TESPS implantation is definite in the treatment of BPH-induced dysuria, and it can be used as a first-choice method for the patients at high risk and unsuitable for surgery. Finasteride has an evident advantage in preventing hematuria and infection after prostatic stent implantation, and long-term medication of finasteride improves long-term outcomes.
Assuntos
Finasterida , Hiperplasia Prostática , Masculino , Humanos , Finasterida/uso terapêutico , Hiperplasia Prostática/cirurgia , Hematúria/etiologia , Estudos Retrospectivos , Resultado do Tratamento , StentsRESUMO
OBJECTIVE: To investigate the clinical and histopathologic features of testicular seminoma with syncytoplasmic trophoblastic components. METHODS: Using light microscopic staining, we analyzed the clinical and histopathologic characteristics, diagnosis, differential diagnosis and prognosis of 3 cases of testicular seminoma with syncytoplasmic trophoblastic components, and reviewed the relevant literature. RESULTS: All the 3 cases were typical seminoma with syncytiotrophoblastic giant cells. Immunohistochemistry showed strong expressions of CD117 OCT-4, SALL4 and PLAP in diffuse tumor cells, and that of hCG in syncytiotrophoblastic cells. Continuous monitoring and consultation exhibited normal levels of serum ß-hCG in all the cases after postoperative chemotherapy. CONCLUSIONS: Testicular seminoma with syncytiotrophoblastic giant cells and increased serum ß-hCG is a rare subtype, which occurs mostly in young people, sensitive to chemotherapy postoperatively and with a relatively good prognosis.
Assuntos
Seminoma/diagnóstico , Neoplasias Testiculares/diagnóstico , Trofoblastos/citologia , Gonadotropina Coriônica/sangue , Células Gigantes/citologia , Humanos , Imuno-Histoquímica , Masculino , Prognóstico , Seminoma/terapia , Neoplasias Testiculares/terapiaRESUMO
OBJECTIVE: To investigate the surgical techniques and clinical effect of Memokath transurethral spiral thermo-expandable prostatic stent (STEPS) implantation in the treatment of BPH. METHODS: From January 2017 to January 2018, 26 BPH patients underwent Memokath transurethral STEPS implantation, 9 under the flexible cystoscope and the other 17 under the rigid cystoscope. The patients were aged 62ï¼91 years old, with a prostate volume of 32ï¼78 ml, postvoid residual urine volume (PVR) of (67.3 ± 11.2) ml, maximum urinary flow rate (Qmax) of (6.3 ± 1.8) ml/s, and IPSS score of 26.7 ± 5.7. Eight of the patients had preoperative urinary retention, of whom, 6 received catheterization and 2 had undergone cystostomy for bladder fistula before STEPS implantation. RESULTS: The operations lasted 15ï¼30 minutes and were successfully completed in 24 cases while stent-shedding occurred in the other 2. Twenty-two of the patients achieved spontaneous urination immediately after surgery and 2 experienced bladder clot embolism. At 3 month after surgery, 24 of the patients showed significant improvement in PVR (ï¼»21.4 ± 7.7ï¼½ ml), Qmax (ï¼»18.3 ± 4.7ï¼½ ml/s) and IPSS (8.3 ± 2.1), and 13 exhibited no statistically significant difference from the baseline in the IIEF-5 score (14.1 ± 1.1 vs 14.3 ± 1.0, P > 0.05). At 12 months, all the patients were found with markedly improved urination but no adverse events except recurrent urinary tract infection in 2 cases. CONCLUSIONS: Memokath STEPS implantation, with its advantages of simple operation, high safety, definite effectiveness, non-influence on sexual function, is a new effective surgical option for the treatment of BPH.
Assuntos
Cistoscopia/métodos , Hiperplasia Prostática/cirurgia , Stents , Idoso , Idoso de 80 Anos ou mais , Cistoscópios , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Resultado do Tratamento , Retenção UrináriaRESUMO
Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts in the human genome which perform crucial functions in diverse biological processes. The abnormal expression of some lncRNAs has been found in tumorigenesis, development and therapy resistance of cancers. They may act as oncogenes or tumour suppressors and can be used as diagnostic or prognostic markers, prompting their therapeutic potentials in cancer treatments. Studies have indicated that many lncRNAs are involved in the regulation of several signal pathways, including Wnt/ß-catenin signalling pathway, which has been reported to play a significant role in regulating embryogenesis, cell proliferation and controlling tumour biology. Emerging evidences have suggested that lncRNAs can interact with several components of the Wnt/ß-catenin signalling pathway to regulate the expression of Wnt target genes in cancer. Moreover, the expression of lncRNAs can also be influenced by the pathway. Nevertheless, Wnt/ß-catenin signalling pathway-related lncRNAs and their interactions in cancer are not systematically analysed before. Considering these, this review emphasized the associations between lncRNAs and Wnt/ß-catenin signalling pathway in cancer initiation, progression and their therapeutic influence. We also provided an overview on characteristics of lncRNAs and Wnt/ß-catenin signalling pathway and discussed their functions in tumour biology. Finally, targeting lncRNAs or/and molecules associated with the Wnt/ß-catenin signalling pathway may be a feasible therapeutic method in the future.
Assuntos
Neoplasias/genética , RNA Longo não Codificante/genética , Via de Sinalização Wnt/genética , Animais , Carcinogênese/genética , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Neoplasias/patologia , RNA Longo não Codificante/metabolismoRESUMO
OBJECTIVES: To produce and characterize novel laccases with ethanol tolerance from Trametes versicolor using agriculture by-products as energy source. RESULTS: Trametes versicolor 1017 produces two laccase isoenzymes with a total activity of 10 U ml(-1) within 8 days when using wheat bran and peanut powder as energy sources in liquid culture medium. A novel isoenzyme, named Tvlac, was identified, purified and characterized. Its optimum pH and temperature were from 4.5 to 5 and 55 to 60 °C, respectively. Its activity was stimulated by ethanol at 10 % (v/v) which increased the V 0. CONCLUSIONS: The biochemical properties of Tvlac substantiate the potential of this enzyme for applications under an aqueous ethanol mixture environment.
Assuntos
Ativadores de Enzimas/metabolismo , Etanol/metabolismo , Lacase/metabolismo , Trametes/enzimologia , Arachis/metabolismo , Meios de Cultura/química , Estabilidade Enzimática , Concentração de Íons de Hidrogênio , Lacase/química , Lacase/genética , Lacase/isolamento & purificação , Temperatura , Trametes/genética , Triticum/metabolismoRESUMO
BACKGROUND: The objective of this study was to modify the adrenal gland-sparing strategy based on retroperitoneal laparoscopic radical nephrectomy by reviewing the anatomic relationship between the kidney and the adrenal gland. METHODS: From June 2010 to October 2012, a total of 68 patients (45 males and 23 females) with localized renal cell carcinoma were treated at our hospital. The study included 35 cases that were right side and 33 cases that were left, and average patient age was 54.06 years. The average tumor size was 4.7 cm. Tumors were classified via the TNM staging system. All patients underwent adrenal gland-sparing surgery based on retroperitoneal laparoscopic radical nephrectomy. RESULTS: For each patient, surgery was successful without conversion to open surgery. The average operative time was 56.65 ± 26.60 min, and the mean blood loss was 70.61 ± 60.96 ml. All patients were discharged from the hospital 3 to 8 days after surgery. During surgery, the adrenal gland was slightly lacerated in three cases and the peritoneum showed perforation in six cases. Only one case recurred during the study follow-up. CONCLUSIONS: Based on retroperitoneal laparoscopy radical nephrectomy, this effective adrenal gland-sparing surgery showed direct exposure of tissue and little interference of the upper pole of the kidney. Elevation of the adrenal gland could help with the complete dissection of the adrenal gland from the kidney. The separation of the kidney was rapid, simple and accurate. The probability of adrenal gland damage was reduced. This strategy is recommended for widespread use in T1-2 renal neoplasms.
Assuntos
Glândulas Suprarrenais/cirurgia , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Laparoscopia , Nefrectomia , Tratamentos com Preservação do Órgão , Espaço Retroperitoneal/cirurgia , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/cirurgia , Glândulas Suprarrenais/patologia , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Espaço Retroperitoneal/patologiaRESUMO
Introduction: Metastatic renal cell carcinoma (mRCC) with sarcomatoid features has a poor prognosis. Cytoreductive radical nephrectomy (CRN) can improve prognosis, but patient selection is unclear. This study aimed to develop a prediction model for selecting patients suitable for CRN. Materials and methods: Patients with a diagnosis of mRCC with sarcomatoid features in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 were retrospectively reviewed. CRN benefit was defined as a survival time longer than the median overall survival (OS) in patients who did not receive CRN. A prediction nomogram was established and validated using the SEER cohort (training and internal validation) and an external validation cohort. Results: Of 900 patients with sarcomatoid mRCC, 608 (67.6%) underwent CRN. OS was longer in the CRN group than in the non-CRN group (8 vs. 6 months, hazard ratio (HR) = 0.767, p = 0.0085). In the matched CRN group, 124 (57.7%) patients survived >6 months after the surgery and were considered to benefit from CRN. Age, T-stage, systematic therapy, metastatic site, and lymph nodes were identified as independent factors influencing OS after CRN, which were included in the prediction nomogram. The monogram performed well on the training set (area under the receiver operating characteristic (AUC) curve = 0.766, 95% confidence interval (CI): 0.687-0.845), internal validation set (AUC = 0.796, 95% CI: 0.684-0.908), and external validation set (AUC = 0.911, 95% CI: 0.831-0.991). Conclusions: A nomogram was constructed and validated with good accuracy for selecting patients with sarcomatoid mRCC suitable for CRN.
RESUMO
There is significant variability with respect to the prognosis of nonmetastatic clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT). By applying multiregion whole-exome sequencing on normal-tumor-thrombus-metastasis quadruples from 33 ccRCC patients, we showed that metastases were mainly seeded by VTT (81.8%) rather than primary tumors (PTs). A total of 706 nonmetastatic ccRCC patients with VTT from three independent cohorts were included in this study. C-index analysis revealed that pathological grading of VTT outperformed other indicators in risk assessment (OS: 0.663 versus 0.501-0.610, 0.667 versus 0.544-0.651, and 0.719 versus 0.511-0.700 for Training, China-Validation, and Poland-Validation cohorts, respectively). We constructed a risk predicting model, TT-GPS score, based on four independent variables: VTT height, VTT grading, perinephric fat invasion, and sarcomatoid differentiation in PT. The TT-GPS score displayed better discriminatory ability (OS, c-index: 0.706-0.840, AUC: 0.788-0.874; DFS, c-index: 0.691-0.717, AUC: 0.771-0.789) than previously reported models in risk assessment. In conclusion, we identified for the first-time pathological grading of VTT as an unheeded prognostic factor. By incorporating VTT grading, the TT-GPS score is a promising prognostic tool in predicting the survival of nonmetastatic ccRCC patients with VTT.
RESUMO
OBJECTIVE: To evaluate the effects of methylation inhibitor 5-Aza-2'-Deoxycytidine (5-aza-2dc) and docetaxel (DT), alone or in combination, on the proliferation, migration, apoptosis and cell cycles of the human prostate cancer cell line PC3, and to investigate the possible mechanisms of these two drugs acting on prostate cancer in vitro. METHODS: Four groups were designed in this experiment: control, 5-aza-2dc, DT, and 5-aza-2dc + DT. The inhibitory effect of 5-aza-2dc and/or DT on the proliferation, migration and invasiveness of PC3 cells was detected by MTT, wound healing assay and cell migration assay, respectively. The apoptosis of the PC3 cells and its relationship with cell cycles were determined by Annexin V-FITC/PI assay and flow cytometry. RESULTS: 5-aza-2dc and/or DT significantly increased the inhibition rate of the PC3 cells, decreased their migration distance and reduced the number of the cells that invaded the lower chamber, most significantly in the 5-aza-2dc + DT group (P < 0.05). The cell apoptosis rates of the control, 5-aza-2dc, DT and 5-aza-2dc + DT groups were (10.65 +/- 0.39)%, (16.60 +/- 0.67)%, (17.95 +/- 1.08)% and (22.98 +/- 1.18)%, respectively, with the most significant increase in the combination group (P < 0.05). Combined medication of 5-aza-2dc and DT remarkably reduced the number of cells in the G0/G1 phase, and increased that in the G2/M phase (P < 0.05). CONCLUSION: 5-aza-2dc and DT, either alone or in combination, can significantly inhibit the proliferation, migration and invasiveness of PC3 cells in vitro, as well as induce their apoptosis and arrest their cell cycles in the G2/M phase, with even more significant effect when used in combination than applied alone.
Assuntos
Apoptose/efeitos dos fármacos , Desoxicitidina/farmacologia , Taxoides/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Desoxicitidina/administração & dosagem , Docetaxel , Sinergismo Farmacológico , Humanos , Masculino , Taxoides/administração & dosagemRESUMO
OBJECTIVE: To investigate the exact age-adjusted incidence (AAI), clinical characteristics, and survival data of collecting duct carcinoma of the kidney (CDCK) recorded in the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. METHODS: Patients with CDCK confirmed by microscopic examination from 2004 to 2018 were selected from the SEER database. AAI rates were calculated using SEER*Stat software (version 8.3.9). The Kaplan-Meier method was used to evaluate cancer-specific survival (CSS) rates according to tumor size, tumor stage, and treatment methods, and differences among these variables were assessed by the log-rank test. Cox regression analysis was employed to identify variables independently related to CSS. RESULTS: A total of 286 patients with CDCK were identified from the database. The majority of the patients were white (69.2%), male (67.5%), and married (60.5%), and the median age was 59 years. Most patients with CDCK (74.4%) presented with stages III or IV disease. The diameter of most (59.4%) tumors was less than 7 cm, and the tumors were more commonly found on the left than on the right (55.2% vs. 44.8%). The incidence of CDCK decreased over time. The median CSS time was 17 months. In terms of the treatment modalities used, 83.9% of the patients underwent surgery; 32.9% underwent chemotherapy, and 13.6% underwent radiotherapy. The CSS rates at 1, 2, and 5 years were 57.3%, 43.2%, and 30.7%, respectively. In patients with stage IV CDCK treated with surgery alone, chemotherapy alone, and surgery plus chemotherapy, the median survival time was 5 months, 9 months, and 14 months, respectively (P =0.024). Multivariate Cox regression analysis showed surgery, chemotherapy, stage, regional lymph node metastasis, and distant metastasis were independent prognostic factors for patients with CDCK. CONCLUSIONS: CDCK is an uncommon malignant renal carcinoma, and its incidence is decreasing based on the analysis of current data. CDCK is a high stage, regional lymph-nodes positive, and metastatic disease. Compared with surgery alone or chemotherapy alone, patients with stage IV could gain survival benefit from surgery combined with chemotherapy.
RESUMO
Sunitinib is widely used as a firstline treatment for advanced renal cell carcinoma (RCC). However, a number of patients with RCC who receive sunitinib develop drug resistance; and the biological mechanisms involved in resistance to sunitinib remain unclear. It has previously been suggested that the protein glutaminylpeptide cyclotransferase (QPCT) is closely related to sunitinib resistance in RCC. Thus, in the present study, in order to further examine the molecular mechanisms responsible for sunitinib resistance in RCC, sunitinibnonresponsive and responsive RCC tissue and plasma samples were collected and additional experiments were performed in order to elucidate the molecular mechanisms responsible for sunitinib resistance in RCC. The upstream and downstream regulatory mechanisms of QPCT were also evaluated. On the whole, the data from the present study suggest that QPCT, CCCTCbinding factor (CTCF) and phosphatidylinositol4,5bisphosphate 3kinase catalytic subunit alpha (PIK3CA) may be used as targets for predicting, reversing and treating sunitinibresistant RCC.
Assuntos
Aminoaciltransferases/metabolismo , Fator de Ligação a CCCTC/metabolismo , Carcinoma de Células Renais/patologia , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias Renais/patologia , Sunitinibe/farmacologia , Células A549 , Animais , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/metabolismo , Masculino , Camundongos , Sunitinibe/uso terapêutico , Regulação para CimaRESUMO
Cancer stem cells (CSCs) are involved in tumorigenesis, recurrence, and therapy resistance. To identify critical regulators of sarcoma CSCs, we performed a reporter-based genome-wide CRISPR-Cas9 screen and uncovered Kruppel-like factor 11 (KLF11) as top candidate. In vitro and in vivo functional annotation defined a negative role of KLF11 in CSCs. Mechanistically, KLF11 and YAP/TEAD bound to adjacent DNA sites along with direct interaction. KLF11 recruited SIN3A/HDAC to suppress the transcriptional output of YAP/TEAD, which, in turn, promoted KLF11 transcription, forming a negative feedback loop. However, in CSCs, this negative feedback was lost because of epigenetic silence of KLF11, causing sustained YAP activation. Low KLF11 was associated with poor prognosis and chemotherapy response in patients with sarcoma. Pharmacological activation of KLF11 by thiazolidinedione effectively restored chemotherapy response. Collectively, our study identifies KLF11 as a negative regulator in sarcoma CSCs and potential therapeutic target.
Assuntos
Sistemas CRISPR-Cas , Sarcoma , Proteínas Reguladoras de Apoptose/metabolismo , Sistemas CRISPR-Cas/genética , Humanos , Células-Tronco Neoplásicas/metabolismo , Proteínas Repressoras/metabolismo , Sarcoma/tratamento farmacológico , Sarcoma/genéticaRESUMO
Prostate cancer is one of the most common malignant tumors in males, and its etiology and pathogenesis remain unclear. Epigenesis is involved in prostate cancer at all stages of the process, and closely related with its growth and metastasis. DNA methylation and histone modification are the most important manifestations of epigenetics in prostate cancer. The mechanisms of carcinogenesis of DNA methylation include whole-genome hypomethylation, aberrant local hypermethylation of promoters and genomic instability. DNA methylation is closely related to the process of prostate cancer, as in DNA damage repair, hormone response, tumor cell invasion/metastasis, cell cycle regulation, and so on. Histone modification causes corresponding changes in chromosome structure and the level of gene transcription, and it may affect the cycle, differentiation and apoptosis of cells, resulting in prostate cancer. Some therapies have been developed targeting the epigenetic changes in prostate cancer, including DNA methyltransferases and histone deacetylase inhibitors, and have achieved certain desirable results.
Assuntos
Epigenômica , Neoplasias da Próstata/genética , Metilação de DNA , Reparo do DNA , Epigênese Genética , Histonas/genética , Humanos , MasculinoRESUMO
Clear cell renal cell carcinoma (ccRCC) is one of the most common tumors in the urinary system. Progression in immunotherapy has provided novel options for the ccRCC treatment. However, the understanding of the ccRCC microenvironment and the potential therapeutic targets in the microenvironment is still unclear. Here, we analyzed the gene expression profile of ccRCC tumors from the Cancer Genome Atlas (TCGA) and calculated the abundance ratios of immune cells for each sample. Then, seven types of immune cells were found to be correlated to overall survival, and 3863 immune-related genes were identified by analyzing differentially expressed genes. We also found that the function of immune-related genes was mainly focused on ligand-receptor binding and signaling pathway transductions. Additionally, we identified 13 hub genes by analyzing the protein-protein interaction network, and seven of them are related to overall survival. Our study not only expands the understanding of fundamental biological features of microenvironment but also provides potential therapeutic targets.