scholarly journals Putting the Brakes on Tumorigenesis with Natural Products of Plant Origin: Insights into the Molecular Mechanisms of Actions and Immune Targets for Bladder Cancer Treatment

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1213
Author(s):  
Qiushuang Wu ◽  
Janet P. C. Wong ◽  
Hang Fai Kwok
Keyword(s):  
Bladder Cancer ◽  
Natural Products ◽  
Cancer Treatment ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Plant Origin ◽  
New Ideas ◽  
Muscle Invasive ◽  
Reduced Toxicity ◽  
Positive Effect

Bladder cancer is the 10th most commonly diagnosed cancer worldwide. Although the incidence in men is 4 times higher than that in women, the diagnoses are worse for women. Over the past 30 years, the treatment for bladder cancer has not achieved a significant positive effect, and the outlook for mortality rates due to muscle-invasive bladder cancer and metastatic disease is not optimistic. Phytochemicals found in plants and their derivatives present promising possibilities for cancer therapy with improved treatment effects and reduced toxicity. In this study, we summarize the promising natural products of plant origin with anti-bladder cancer potential, and their anticancer mechanisms—especially apoptotic induction—are discussed. With the developments in immunotherapy, small-molecule targeted immunotherapy has been promoted as a satisfactory approach, and the discovery of novel small molecules against immune targets for bladder cancer treatment from products of plant origin represents a promising avenue of research. It is our hope that this could pave the way for new ideas in the fields of oncology, immunology, phytochemistry, and cell biology, utilizing natural products of plant origin as promising drugs for bladder cancer treatment.

scholarly journals Androgen Receptor Signaling Induces Cisplatin Resistance via Down-Regulating GULP1 Expression in Bladder Cancer

2021 ◽  
Vol 22 (18) ◽  
pp. 10030
Author(s):  
Yuki Teramoto ◽  
Guiyang Jiang ◽  
Takuro Goto ◽  
Taichi Mizushima ◽  
Yujiro Nagata ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Androgen Receptor ◽  
Molecular Mechanisms ◽  
Direct Interaction ◽  
Androgen Treatment ◽  
Downstream Effector ◽  
Bladder Cancer Cells ◽  
Cisplatin Sensitivity ◽  
Muscle Invasive

The underlying molecular mechanisms of resistance to cisplatin-based systemic chemotherapy in bladder cancer patients remain to be elucidated, while the link between androgen receptor (AR) activity and chemosensitivity in urothelial cancer has been implicated. Our DNA microarray analysis in control vs. AR knockdown bladder cancer lines identified GULP1 as a potential target of AR signaling. We herein determined the relationship between AR activity and GULP1 expression in bladder cancer cells and then assessed the functional role of GULP1 in cisplatin sensitivity. Androgen treatment in AR-positive cells or AR overexpression in AR-negative cells considerably reduced the levels of GULP1 expression. Chromatin immunoprecipitation further showed direct interaction of AR with the promoter region of GULP1. Meanwhile, GULP1 knockdown sublines were significantly more resistant to cisplatin treatment compared with respective controls. GULP1 knockdown also resulted in a significant decrease in apoptosis, as well as a significant increase in G2/M phases, when treated with cisplatin. In addition, GULP1 was immunoreactive in 74% of muscle-invasive bladder cancers from patients who had subsequently undergone neoadjuvant chemotherapy, including 53% of responders showing moderate (2+)/strong (3+) expression vs. 23% of non-responders showing 2+/3+ expression (P = 0.044). These findings indicate that GULP1 represents a key downstream effector of AR signaling in enhancing sensitivity to cisplatin treatment.

scholarly journals Identification and Immunocorrelation of Prognosis-Related Genes Associated With Development of Muscle-Invasive Bladder Cancer

2021 ◽  
Vol 7 ◽  
Author(s):  
Jingxian Li ◽  
Yantao Lou ◽  
Shuai Li ◽  
Fei Sheng ◽  
Shuaibing Liu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Molecular Mechanisms ◽  
Low Risk ◽  
Enrichment Score ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Immune Infiltration ◽  
Stratification Method ◽  
Significant Difference ◽  
Muscle Invasive

Improved understanding of the molecular mechanisms and immunoregulation of muscle-invasive bladder cancer (MIBC) is essential to predict prognosis and develop new targets for therapies. In this study, we used the cancer genome atlas (TCGA) MIBC and GSE13507 datasets to explore the differential co-expression genes in MIBC comparing with adjacent non-carcinoma tissues. We firstly screened 106 signature genes by Weighted Gene Co-expression Network Analysis (WGCNA) and further identified 15 prognosis-related genes of MIBC using the univariate Cox progression analysis. Then we systematically analyzed the genetic alteration, molecular mechanism, and clinical relevance of these 15 genes. We found a different expression alteration of 15 genes in MIBC comparing with adjacent non-carcinoma tissues and normal tissues. Meanwhile, the biological functions and molecular mechanisms of them were also discrepant. Among these, we observed the ANLN was highly correlated with multiple cancer pathways, molecular function, and cell components, revealing ANLN may play a pivotal role in MIBC development. Next, we performed a consensus clustering of 15 prognosis-related genes; the results showed that the prognosis, immune infiltration status, stage, and grade of MIBC patients were significantly different in cluster1/2. We further identified eight-genes risk signatures using the least absolute shrinkage and selection operator (LASSO) regression analysis based on the expression values of 15 prognosis-related genes, and also found a significant difference in the prognosis, immune infiltration status, stage, grade, and age in high/low-risk cohort. Moreover, the expression of PD-1, PD-L1, and CTLA4 was significantly up-regulated in cluster1/high-risk-cohort than that in cluster2/low-risk-cohort. High normalized enrichment score of the Mitotic spindle, mTORC1, Complement, and Apical junction pathway suggested that they might be involved in the distinct tumor immune microenvironment (TIME) of cluster1/2 and high-/low-risk-cohort. Our study identified 15 prognosis-related genes of MIBC, provided a feasible stratification method to help for the future immunotherapy strategies of MIBC patients.

The challenges of Bacillus of Calmette-Guerin (BCG) therapy for high risk non muscle invasive bladder cancer treatment in older patients

2018 ◽  
Vol 9 (5) ◽  
pp. 507-512 ◽  
Author(s):  
Marco Racioppi ◽  
Luca Di Gianfrancesco ◽  
Mauro Ragonese ◽  
Giuseppe Palermo ◽  
Emilio Sacco ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Cancer Treatment ◽  
Older Patients ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Bcg Therapy ◽  
Muscle Invasive

Intravesical Thalidomide boosts bacillus Calmette-Guérin (BCG) in non-muscle invasive bladder cancer treatment

2017 ◽  
Vol 35 (1) ◽  
Author(s):  
Gabriela R. Passos ◽  
Juliana A. Camargo ◽  
Karen L. Ferrari ◽  
Mário J. A. Saad ◽  
Amilcar C. de Mattos ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Treatment ◽  
Invasive Bladder Cancer ◽  
Bacillus Calmette Guerin ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

scholarly journals Oncological outcomes of high-grade T1 non-muscle-invasive bladder cancer treatment in octogenarians

2021 ◽  
Author(s):  
Aleksander Ślusarczyk ◽  
Karolina Garbas ◽  
Piotr Zapała ◽  
Łukasz Zapała ◽  
Piotr Radziszewski
Keyword(s):  
Bladder Cancer ◽  
Cancer Treatment ◽  
Charlson Comorbidity Index ◽  
Invasive Bladder Cancer ◽  
High Grade ◽  
Muscle Invasive Bladder Cancer ◽  
Oncological Outcomes ◽  
Bcg Therapy ◽  
Comorbidity Index ◽  
Muscle Invasive

Abstract Purpose To evaluate the outcomes of high-grade T1 non-muscle-invasive bladder cancer treatment (NMIBC) in elderly patients over 80 years of age. Methods This is a retrospective single tertiary-centre study. Medical records of patients with T1 high-grade NMIBC treated with transurethral resection of the bladder tumour (TURBT) were reviewed. Among 269 patients with high-grade T1 NMIBC, 74 individuals were over 80 years of age at the time of surgery. Finally, 67 patients met the inclusion criteria. Results Only 47.8% of patients (N = 32) received at least five of the six instillations of the BCG immunotherapy induction course. Oncological outcomes were compared between patients who received at least the induction course of BCG and non-BCG-treated patients matched to each other based on age and Charlson comorbidity index. Thirty case–control pairs were included in the final analysis. Rates of disease recurrence (80% vs. 53%) and cancer-specific mortality (40% vs. 10%) were significantly higher in the group of patients who did not receive BCG. BCG therapy, Charlson comorbidity index, haemoglobin concentration and the number of tumours > 3 in TURBT constituted independent prognostic factors for cancer-specific survival (CSS). Conclusion BCG should be strongly recommended to patients with T1HG NMIBC despite advanced age and comorbidities. Already BCG induction improves CSS and reduces the recurrence rate in octogenarians with T1HG bladder cancer.

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