scholarly journals Aristolochic Acid and Immunotherapy for Urothelial Carcinoma: Directions for unmet Needs

2019 ◽  
Vol 20 (13) ◽  
pp. 3162 ◽  
Author(s):  
Huang-Yu Yang ◽  
Chih-Chao Yang ◽  
Chao-Yi Wu ◽  
Li-Jen Wang ◽  
Kun-Lin Lu
Keyword(s):  
Urothelial Carcinoma ◽  
Somatic Mutations ◽  
Aristolochic Acid ◽  
Suppressor Gene ◽  
Immune Checkpoint Blockade ◽  
Current State ◽  
Close Relationship ◽  
Tp53 Tumor Suppressor Gene ◽  
Treatment Responses ◽  
Carcinoma Of The Bladder

Urothelial carcinoma of the bladder (UCB) and upper tracts (UTUC) used to share management with similar principles. However, their genetic and epigenetic differences along with different responses to immunotherapy were recently identified, which are reminiscent of their distinct etiologies. Different from the variety of environmental factors relating to UCB, UTUC is best known for its close relationship with exposure to aristolochic acid (AA). AA is believed to cause its carcinogenicity through forming DNA adducts of deoxyadenosine-aristolactam, as well as A:T → T:A transversions in the TP53 tumor suppressor gene. Since recent findings suggested that cancers with higher somatic mutations are associated with better treatment responses upon immune checkpoint blockade, UTUC and AA-related biomarkers reasonably serve as good candidates, as well as a potential prognostic predictor for the flourishing immunotherapy. This review covers the current state of the literature on the clinical response of UTUC and UCB receiving immunotherapy and points out directions for refinement regarding patient selection.

Genomic alterations in upper tract urothelial carcinoma (UTUC) versus urothelial carcinoma of the bladder (UBC).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 431-431
Author(s):  
Stephanie A. Mullane ◽  
Guillermo de Velasco ◽  
Toni K. Choueiri ◽  
Philip W. Kantoff ◽  
Joaquim Bellmunt
Keyword(s):  
Urothelial Carcinoma ◽  
Somatic Mutations ◽  
Tumor Stage ◽  
Copy Number Alterations ◽  
Sequencing Data ◽  
Genomic Alterations ◽  
Biologically Relevant ◽  
Somatic Alterations ◽  
Tumor Sequencing ◽  
Carcinoma Of The Bladder

431 Background: Defining the landscape of genomic alterations in UTUC as well as identifying the genomic differences from UBC, may provide insights into the treatment of UTUC. Methods: We interrogated our enterprise-wide institutional targeted next generation tumor sequencing data to compare genomic alterations in patients with UTUC (n = 25) with UBC (n = 72), irrespective of tumor stage. We described differences in frequencies of somatic mutations and copy number alterations in 300 relevant cancer-associated genes. Results: UTUC and UBC demonstrated differences in somatic alterations. Genes more commonly found in UTUC included FGFR3 (20% v. 7.5%), STAG2 (16% v. 7.5%), RB1 (24% v. 16%), TSC1 (16% v. 5.4%), EP300 (12% v. 5.4%), IGFIR (20% v. 0%), and Notch1 (24% v. 0%) (see table). Alterations in FGFR3 and TP53 co-existed in only on patient. We did identify two UTUC patients with MSH2 alterations, both of whom had previously been diagnosed with Lynch Syndrome. Conclusions: Biologically relevant differences exist between UTUC and UBC. We observed an enrichment of potentially targetable mutations including TSC1 and FGFR3. Findings in the genomic profile underline the need to consider these two locations as unique entities for future biologically driven trials. [Table: see text]

scholarly journals Molecular Predictors of Complete Response Following Neoadjuvant Chemotherapy in Urothelial Carcinoma of the Bladder and Upper Tracts

2019 ◽  
Vol 20 (4) ◽  
pp. 793 ◽  
Author(s):  
Jennifer Tse ◽  
Rashed Ghandour ◽  
Nirmish Singla ◽  
Yair Lotan
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Urothelial Carcinoma ◽  
Tyrosine Kinases ◽  
Standard Of Care ◽  
Complete Response ◽  
Pathological Examination ◽  
Current State ◽  
Response To Chemotherapy ◽  
Carcinoma Of The Bladder ◽  
Repair Genes

Urothelial carcinoma of the bladder (UCB) and upper tracts (UTUC) is often regarded as one entity and is managed generally with similar principles. While neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is an established standard of care in UCB, strong evidence for a similar approach is lacking in UTUC. The longest survival is seen in patients with complete response (pT0) on pathological examination of the RC specimen, but impact of delayed RC in nonresponders may be detrimental. The rate of pT0 following NAC in UTUC is considerably lower than that in UCB due to differences in access and instrumentation. Molecular markers have been evaluated to try to predict response to chemotherapy to reduce unnecessary treatment and expedite different treatment for nonresponders. A variety of potential biomarkers have been evaluated to predict response to cisplatin based chemotherapy including DNA repair genes (ATM, RB1, FANCC, ERCC2, BRCA1, and ERCC1), regulators of apoptosis (survivin, Bcl-xL, and emmprin), receptor tyrosine kinases (EGFR and erbB2), genes involved in cellular efflux (MDR1 and CTR1), in addition to molecular subtypes (Basal, luminal, and p53-like). The current state of the literature on the prediction of response to NAC based on the presence of these biomarkers is discussed in this review.

Incidentally Discovered Osseous Metaplasia Within High-grade Urothelial Carcinoma of the Bladder

Urology ◽  
2012 ◽  
Vol 79 (4) ◽  
pp. e59-e60 ◽  
Author(s):  
Anne G. Dudley ◽  
Jeffrey J. Tomaszewski ◽  
Amber H. Hughes ◽  
Benjamin J. Davies
Keyword(s):  
Urothelial Carcinoma ◽  
Osseous Metaplasia ◽  
High Grade ◽  
Carcinoma Of The Bladder

scholarly journals Antitumor Effects of PRIMA-1 and PRIMA-1Met (APR246) in Hematological Malignancies: Still a Mutant P53-Dependent Affair?

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 98
Author(s):  
Paola Menichini ◽  
Paola Monti ◽  
Andrea Speciale ◽  
Giovanna Cutrona ◽  
Serena Matis ◽  
...  
Keyword(s):  
Hematological Malignancies ◽  
Cell Metabolism ◽  
Therapy Response ◽  
Tp53 Gene ◽  
Suppressor Gene ◽  
Lower Percentage ◽  
Mutant P53 ◽  
Wild Type ◽  
Antitumor Effects ◽  
Tp53 Tumor Suppressor Gene

Because of its role in the regulation of the cell cycle, DNA damage response, apoptosis, DNA repair, cell migration, autophagy, and cell metabolism, the TP53 tumor suppressor gene is a key player for cellular homeostasis. TP53 gene is mutated in more than 50% of human cancers, although its overall dysfunction may be even more frequent. TP53 mutations are detected in a lower percentage of hematological malignancies compared to solid tumors, but their frequency generally increases with disease progression, generating adverse effects such as resistance to chemotherapy. Due to the crucial role of P53 in therapy response, several molecules have been developed to re-establish the wild-type P53 function to mutant P53. PRIMA-1 and its methylated form PRIMA-1Met (also named APR246) are capable of restoring the wild-type conformation to mutant P53 and inducing apoptosis in cancer cells; however, they also possess mutant P53-independent properties. This review presents the activities of PRIMA-1 and PRIMA-1Met/APR246 and describes their potential use in hematological malignancies.

scholarly journals Rectal metastasis from bladder urothelial carcinoma: a case report

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yuki Ii ◽  
Shinya Munakata ◽  
Kumpei Honjo ◽  
Masaya Kawai ◽  
Shingo Kawano ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Tumor Resection ◽  
Disease Recurrence ◽  
Small Areas ◽  
Metastatic Urothelial Carcinoma ◽  
Rare Site ◽  
Difficult Defecation ◽  
Carcinoma Of The Bladder ◽  
Transitional Cells ◽  
Rectal Metastasis

Abstract Background Urothelial carcinoma arises from transitional cells in the urothelial tract. In advanced cases, it can metastasize locally to surrounding organs or distally to organs such as the lungs, bones, or liver. Here we describe a case of rectal metastasis from urothelial carcinoma treated with multiple sessions of transurethral resection of bladder tumor (TURBT). Case presentation A 72-year-old woman presented to our department with abdominal bloating andobstructed defecation. She had undergone two sessions of TURBT for early urothelial carcinoma in another hospital at 64 and 65 months ago, respectively. Cystoscopy at 3 months after the second TURBT session had indicated disease recurrence, and thus, she had been referred to our hospital for further examination, followed by TURBT for the third time at 59 months ago and for the fourth time at 48 months ago; thereafter, she had been followed up with cystoscopy every 6 months without any recurrence. However, she returned to our hospital, complaining of difficult defecation. Subsequent colonoscopy demonstrated an obstructive tumor in the rectum, which was pathologically diagnosed as metastatic urothelial carcinoma of the bladder. Laparoscopic examination revealed two small areas of peritoneal dissemination in the pelvis. A sigmoid colostomy was performed without rectal tumor resection. She has been receiving chemotherapy and is still alive 10 months after surgery. Conclusions Rectal metastasis is a rare site of metastasis for urothelial carcinomas. It is important to consider the possibility of annular rectal constriction caused by infiltrating or metastasizing urothelial carcinoma when managing patients with urothelial carcinoma and with difficult defecation.

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