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Renal cell carcinoma with rhabdoid features (RCC-RF) is an aggressive histologic variant in the adults and is usually unresponsive to standard chemotherapy. Expression of SMARCB1/INI1 was examined in primary RCC-RF (n = 5). Stable INI1 with/without prostaglandin E2 receptor 1 (EP1) knockdown cell lines were created in the ACHN and 786-O RCC cell lines and measured for epidermal growth factor receptor (EGFR)-related signaling pathways. Chemosensitivity to targeted drugs in vitro was tested after knocking down of INI1 in both cell lines. The outcome of co-targeting of INI1 and EP1 in RCC was examined using a tumorigenicity assay. Expression of INI1 was markedly reduced at both transcriptional and translational levels in primary RCC-RF. Immunohistochemical expression of INI1 protein was lost in the nuclei of rhabdoid cells compared with conventional RCC (n = 8). Using two cell lines with different genetic background, we showed that knocking down of INI1 activates the EGFR signaling with up-regulated AKT and ERK pathways and sensitizes cancer cells to Erlotinib treatment in vitro. However, cell-line dependent effects were also demonstrated with reference to impact of INI1 or EP1 on cell growth, migration and response to Gefitinib or Everolimus treatment in vitro. Inactivation of INI1 may play a role in the pathogenesis of RCC-RF. Erlotinib is recommended in the management of patients with INI1-related RCC.
Yi-Wen Wang; Hsiang-Lin Song; Cheng-Yao Chiang; Hong-Fang Song; Hong-Yi Chang; Chien-An Chu; Yih-Lin Tuan; Kun-Hao Tsai; Yin-Chien Ou; Nan-Haw Chow; Yuh-Shyan Tsai. The significance of SMARCB1 in the pathogenesis of renal cell carcinoma with rhabdoid features. Translational Oncology 2021, 14, 101175 .
AMA StyleYi-Wen Wang, Hsiang-Lin Song, Cheng-Yao Chiang, Hong-Fang Song, Hong-Yi Chang, Chien-An Chu, Yih-Lin Tuan, Kun-Hao Tsai, Yin-Chien Ou, Nan-Haw Chow, Yuh-Shyan Tsai. The significance of SMARCB1 in the pathogenesis of renal cell carcinoma with rhabdoid features. Translational Oncology. 2021; 14 (10):101175.
Chicago/Turabian StyleYi-Wen Wang; Hsiang-Lin Song; Cheng-Yao Chiang; Hong-Fang Song; Hong-Yi Chang; Chien-An Chu; Yih-Lin Tuan; Kun-Hao Tsai; Yin-Chien Ou; Nan-Haw Chow; Yuh-Shyan Tsai. 2021. "The significance of SMARCB1 in the pathogenesis of renal cell carcinoma with rhabdoid features." Translational Oncology 14, no. 10: 101175.
Objectives: This study aimed at investigating the prognostic impact of tumor necrosis and preoperative monocyte-to-lymphocyte ratio (MLR) in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Methods: A total of 521 patients with UTUC treated with RNU from January 2008 to June 2019 at our institution were enrolled. Histological tumor necrosis was defined as the presence of microscopic coagulative necrosis. The optimal value of MLR was determined as 0.4 by receiver operating characteristic (ROC) analysis based on cancer-specific mortality. The Kaplan–Meier method with log-rank test and Cox proportional hazards regression models were performed to evaluate the impact of tumor necrosis and MLR on overall (OS), cancer-specific (CSS), and recurrence-free survival (RFS). Furthermore, ROC analysis was used to estimate the predictive ability of potential prognostic factors for oncological outcomes. Results: Tumor necrosis was present in 106 patients (20%), which was significantly associated with tumor location, high pathological tumor stage, lymph node metastasis, high tumor grade, lymphovascular invasion, tumor size, and increased monocyte counts. On multivariate analysis, the combination of tumor necrosis and preoperative MLR was an independent prognosticator of OS, CSS, and RFS (all p< 0.05). Moreover, ROC analyses revealed the predictive accuracy of a combination of tumor necrosis and preoperative MLR for OS, CSS, and RFS with the area under the ROC curve of 0.745, 0.810, and 0.782, respectively (all p< 0.001). Conclusions: The combination of tumor necrosis and preoperative MLR can be used as an independent prognosticator in patients with UTUC after RNU. The identification of this combination could help physicians to recognize high-risk patients with unfavorable outcomes and devise more appropriate postoperative treatment plans.
Kun-Che Lin; Hau-Chern Jan; Che-Yuan Hu; Yin-Chien Ou; Yao-Lin Kao; Wen-Horng Yang; Chien-Hui Ou. Tumor Necrosis with Adjunction of Preoperative Monocyte-to-Lymphocyte Ratio as a New Risk Stratification Marker Can Independently Predict Poor Outcomes in Upper Tract Urothelial Carcinoma. Journal of Clinical Medicine 2021, 10, 2983 .
AMA StyleKun-Che Lin, Hau-Chern Jan, Che-Yuan Hu, Yin-Chien Ou, Yao-Lin Kao, Wen-Horng Yang, Chien-Hui Ou. Tumor Necrosis with Adjunction of Preoperative Monocyte-to-Lymphocyte Ratio as a New Risk Stratification Marker Can Independently Predict Poor Outcomes in Upper Tract Urothelial Carcinoma. Journal of Clinical Medicine. 2021; 10 (13):2983.
Chicago/Turabian StyleKun-Che Lin; Hau-Chern Jan; Che-Yuan Hu; Yin-Chien Ou; Yao-Lin Kao; Wen-Horng Yang; Chien-Hui Ou. 2021. "Tumor Necrosis with Adjunction of Preoperative Monocyte-to-Lymphocyte Ratio as a New Risk Stratification Marker Can Independently Predict Poor Outcomes in Upper Tract Urothelial Carcinoma." Journal of Clinical Medicine 10, no. 13: 2983.
External urethral sphincter (EUS) dysfunction is a common, bothersome female voiding dysfunction. This study aims to analyze the characteristics of different types of female EUS dysfunction, as well as to determine the outcome predictors of sphincteric botulinum toxin A (BoNT-A) injection. Women receiving sphincteric BoNT-A injections for refractory EUS dysfunction were retrospectively reviewed. A comparison of the baseline clinical, urodynamic parameters and the treatment responses were made for patients with different EUS dysfunctions. A total of 106 females were included. Significantly increased detrusor overactivity, detrusor contracting pressure and the bladder outlet obstruction index with decreased urge sensation were noted in patients diagnosed with dysfunctional voiding or detrusor sphincter dyssynergia comparing to those diagnosed with poor relaxation of the external urethral sphincter. The average subjective improvement rate was 67% for the injection. The therapeutic effect was not affected by the type of EUS dysfunction. The multivariate analysis revealed that bladder neck narrowing and catheterization history were predictive of negative outcomes. There is a distinct urodynamic presentation for each type of female EUS dysfunction. Sphincteric BoNT-A injection provides a good therapeutic outcome for refractory EUS dysfunction. A narrowing bladder neck and a history of catheterization suggest poor therapeutic outcomes.
Yin-Chien Ou; Kuan-Hsun Huang; Hau-Chern Jan; Hann-Chorng Kuo; Yao-Lin Kao; Kuen-Jer Tsai. Therapeutic Efficacy of Urethral Sphincteric Botulinum Toxin Injections for Female Sphincter Dysfunctions and a Search for Predictive Factors. Toxins 2021, 13, 398 .
AMA StyleYin-Chien Ou, Kuan-Hsun Huang, Hau-Chern Jan, Hann-Chorng Kuo, Yao-Lin Kao, Kuen-Jer Tsai. Therapeutic Efficacy of Urethral Sphincteric Botulinum Toxin Injections for Female Sphincter Dysfunctions and a Search for Predictive Factors. Toxins. 2021; 13 (6):398.
Chicago/Turabian StyleYin-Chien Ou; Kuan-Hsun Huang; Hau-Chern Jan; Hann-Chorng Kuo; Yao-Lin Kao; Kuen-Jer Tsai. 2021. "Therapeutic Efficacy of Urethral Sphincteric Botulinum Toxin Injections for Female Sphincter Dysfunctions and a Search for Predictive Factors." Toxins 13, no. 6: 398.
Neurogenic and non-neurogenic urethral sphincter dysfunction are common causes of voiding dysfunction. Injections of botulinum toxin A (BoNT-A) into the urethral sphincter have been used to treat urethral sphincter dysfunction (USD) refractory to conventional treatment. Since its first use for patients with detrusor sphincter dyssynergia in 1988, BoNT-A has been applied to various causes of USD, including dysfunctional voiding, Fowler’s syndrome, and poor relaxation of the external urethral sphincter. BoNT-A is believed to decrease urethral resistance via paralysis of the striated sphincter muscle through inhibition of acetylcholine release in the neuromuscular junction. Recovery of detrusor function in patients with detrusor underactivity combined with a hyperactive sphincter also suggested the potential neuromodulation effect of sphincteric BoNT-A injection. A large proportion of patients with different causes of USD report significant improvement in voiding after sphincteric BoNT-A injections. However, patient satisfaction might not increase with an improvement in the symptoms because of concomitant side effects including exacerbated incontinence, urinary urgency, and over-expectation. Nonetheless, in terms of efficacy and safety, BoNT-A is still a reasonable option for refractory voiding function. To date, studies focusing on urethral sphincter BoNT-A injections have been limited to the heterogeneous etiologies of USD. Further well-designed studies are thus needed.
Yao-Lin Kao; Kuan-Hsun Huang; Hann-Chorng Kuo; Yin-Chien Ou. The Therapeutic Effects and Pathophysiology of Botulinum Toxin A on Voiding Dysfunction Due to Urethral Sphincter Dysfunction. Toxins 2019, 11, 728 .
AMA StyleYao-Lin Kao, Kuan-Hsun Huang, Hann-Chorng Kuo, Yin-Chien Ou. The Therapeutic Effects and Pathophysiology of Botulinum Toxin A on Voiding Dysfunction Due to Urethral Sphincter Dysfunction. Toxins. 2019; 11 (12):728.
Chicago/Turabian StyleYao-Lin Kao; Kuan-Hsun Huang; Hann-Chorng Kuo; Yin-Chien Ou. 2019. "The Therapeutic Effects and Pathophysiology of Botulinum Toxin A on Voiding Dysfunction Due to Urethral Sphincter Dysfunction." Toxins 11, no. 12: 728.