Management of Urothelial Bladder Cancer in Clinical Practice: Real-World Answers to Difficult Questions

Mar, Nataliya; Dayyani, Farshid

doi:10.1200/jop.19.00215

Cited by 27 publications

(22 citation statements)

References 53 publications

(74 reference statements)

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“…7 Other challenges include a debate about inclusion of infiltrating immune cells or tumor cells in PD-L1 scoring, intra and intertumoral heterogeneity of PD-L1 expression, and evolution of PD-L1 status with development of treatment resistance. 17 Other predictive biomarkers are being actively investigated. TMB is an independent predictor of response to checkpoint inhibitors in various cancers.…”

Section: Discussionmentioning

confidence: 99%

Metastatic penile squamous cell carcinoma with dramatic response to combined checkpoint blockade with ipilimumab and nivolumab

Baweja

Mar

2020

J Oncol Pharm Pract

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Introduction Prognosis for patients with lymph node positive or metastatic penile squamous cell carcinoma remains poor. Chemotherapy with paclitaxel, ifosfamide, and cisplatin (TIP regimen) is recommended as a first-line option in this cohort of patients. No standard preferred subsequent-line therapy exists for patients with relapsed or refractory penile carcinoma following TIP chemotherapy. Molecular pathogenesis of penile cancer can be subdivided into human papilloma virus-dependent and human papilloma virus-independent pathways. Recent studies have demonstrated increased expression of programmed death ligand-1 in some penile tumors, commonly those that are human papilloma virus-negative. Given the rarity of penile carcinoma in industrialized countries and lack of effective therapies, checkpoint inhibitors may be an attractive treatment option for this subset of patients. Case report We report a case of metastatic penile cancer refractory to TIP chemotherapy, with a dramatic treatment response to ipilimumab and nivolumab. Molecular profiling of this tumor showed a high programmed death ligand-1 expression, high tumor mutational burden, high microsatellite instability, and alterations in DNA mismatch repair genes. Discussion This case highlights another dimension of information that may be gained with molecular genomic profiling of penile tumors, providing insight into the biologic behavior of this neoplasm and assessing for predictive biomarkers of response to immune checkpoint inhibitors.

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Section: Discussionmentioning

confidence: 99%

Metastatic penile squamous cell carcinoma with dramatic response to combined checkpoint blockade with ipilimumab and nivolumab

Baweja

Mar

2020

J Oncol Pharm Pract

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“… 25 Distant metastases and lymph node involvement are correlated with poor prognosis. 26 , 27 Thus, it is critical to identify the novel therapeutic target to improve the clinical outcomes. In the current study, our data showed that ANXA8 and TUG1 were elevated, whereas miR-140-3p was downregulated in bladder cancer tissues and cells.…”

Section: Discussionmentioning

confidence: 99%

Annexin A8 regulated by lncRNA-TUG1/miR-140-3p axis promotes bladder cancer progression and metastasis

Yuan

Chen

et al. 2021

Molecular Therapy - Oncolytics

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Bladder cancer is the ninth most diagnosed cancer in the world. This study aims to investigate the role and mechanisms of the taurine-upregulated gene 1 (TUG1)/miR-140-3p/ annexin A8 ( ANXA8 ) axis in bladder cancer. Western blotting and qRT-PCR determined the expression levels of ANXA8 , miR-140-3p, TUG1, and epithelial-mesenchymal transition (EMT) markers. RNA immunoprecipitation (RIP), luciferase assay, and RNA pull-down assay validated the association among ANXA8, miR-140-3p, and TUG1. The biological functions were determined by colony formation, Annexin V-fluorescein isothiocyanate (FITC)/propidium (PI) staining, and transwell assays. Xenograft tumorigenesis detected tumor growth and metastasis in vivo . Pathological analysis was examined by hematoxylin and eosin (H&E) and immunohistochemistry (IHC) analyses. ANXA8 was elevated in bladder tumors and cells. Knockdown of ANXA8 suppressed cell growth, migration, invasion, and EMT in UMUC-3 and T24 cells. ANXA8 was determined as a miR-140-3p target gene. Overexpression of miR-140-3p suppressed cell proliferation, migration, invasion, and EMT via targeting ANXA8. TUG1 promoted ANXA8 expression via sponging miR-140-3p. Silencing of miR-140-3p or ANXA8 overexpression abrogated the tumor-suppressive effects of TUG1 silencing on bladder cancer cell growth and metastasis. The TUG1/miR-140-3p/ANXA8 axis was also implicated in tumor growth and lung metastasis in vivo . TUG1 promotes bladder cancer progression and metastasis through activating ANXA8 by sponging miR-140-3p, which sheds light on the mechanisms of bladder cancer pathogenesis.

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“…Morphological changes in the heart of rats after serial intravesical administration of Doxorubicin algorithms, more and more newly diagnosed cases (up to 75% according to some data) are superficial bladder cancer, when the tumor affects only the mucous membrane or submucosal layer [1]. Transurethral resection of the tumor is a common standard in the treatment of patients with superficial bladder cancer [12,22]. Intravesical chemotherapy and/or immunotherapy are used as adj uvant therapy after transurethral resection to prevent the development of residual and recurrent neoplasms [17,25].…”

Section: Reports Of Morphologymentioning

confidence: 99%

Morphological changes in the heart of rats after serial intravesical administration of Doxorubicin

Kostiuk

Hodovan

Gormash³

et al. 2021

Rep. of Morph.

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Along with a pronounced antitumor effect, Doxorubicin causes systemic effects with damage to vital organs, including the heart. It prompts the search for ways to prevent the cardiotoxic effect of the drug, one of which could be its intravesical administration. The aim of the study was to develop a method of serial intravesical administration of Doxorubicin in medium therapeutic doses in an experiment and to evaluate the cardiotoxic effect of the drug. 42 female Wistar rats were included in the study. The control group consisted of 7 intact rats. The experimental group consisted of 35 rats who received intravesical chemotherapy with Doxorubicin at a dose of 5 mg/kg once a week for 5 weeks. On days 7th, 14th, 21st, 28th, 35th the hearts of experimental animals were taken for morphological examination. Histomorphometrically determined: the diameter of cardiomyocytes (in the middle part) and the transverse diameter of their nucleus, the width of the interstitial space (endo- and perimysium). The data of histomorphological and histomorphometric examination of the myocardium testified that all animals of the experimental group had a circulatory disorder in the heart muscle at the level of hemomicrocirculation. Such changes led to cardiomyocyte hypotrophy, interstitial edema and fibrosis. During intravesical chemotherapy, the animals showed marked changes in the myocardium, such as expansion of the endomysial zone, due to capillary congestion and edema, in comparison with animals of the intact group. At the end of the experiment, the animals of the experimental group retained the expansion of the endomysial zone, mainly due to interstitial fibrosis. Such changes indicate myocardial hypoxemia with damage and death of cardiomyocytes, activation of interstitial and replacement collagen formation. The obtained morphological data partially indicate the development of dilated cardiomyopathy in experimental animals. However, these changes were less pronounced than the previously described changes that occur after systemic administration of the drug. Additional studies of the electrophysiological activity of the heart and biochemical markers will make it possible to fully assess the degree of cardiotoxicity of Doxorubicin after its intravesical administration. Thus, serial intravesical administration of Doxorubicin in moderate therapeutic doses according to the proposed method causes changes in the myocardium of experimental animals, which are partially similar to the changes in the heart of people receiving chemotherapy with this drug.

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Management of Urothelial Bladder Cancer in Clinical Practice: Real-World Answers to Difficult Questions

Cited by 27 publications

References 53 publications

Metastatic penile squamous cell carcinoma with dramatic response to combined checkpoint blockade with ipilimumab and nivolumab

Metastatic penile squamous cell carcinoma with dramatic response to combined checkpoint blockade with ipilimumab and nivolumab

Annexin A8 regulated by lncRNA-TUG1/miR-140-3p axis promotes bladder cancer progression and metastasis

Morphological changes in the heart of rats after serial intravesical administration of Doxorubicin

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