A novel mouse model of upper tract urothelial carcinoma highlights the impact of dietary intervention on gut microbiota and carcinogenesis prevention despite carcinogen exposure.

Animal models of N-butyl-N-(4-hydroxy butyl) nitrosamine (BBN)-induced urothelial carcinoma (UC), particularly bladder cancer (BC), have long been established. However, the rare incidence of BBN-induced upper urinary tract UC (UTUC), which originates from the same urothelium as BC, remains elusive. The scarcity of animal models of UTUC has made it challenging to study the biology of UTUC.

GDF15 propeptide promotes bone metastasis of castration-resistant prostate cancer by augmenting the bone microenvironment.

Background: Bone metastasis (BM) is a common and fatal condition in patients with castration-resistant prostate cancer (CRPC). However, there are no useful blood biomarkers for CRPC with BM, and the mechanism underlying BM is unclear. In this study, we investigated precise blood biomarkers for evaluating BM that can improve the prognosis of patients with CRPC.

Inflammatory Cell Infiltration Into Islets Without PD-L1 Expression Is Associated With the Development of Immune Checkpoint Inhibitor-Related Type 1 Diabetes in Genetically Susceptible Patients.

Immune checkpoint inhibitors (ICIs) could cause type 1 diabetes (T1D). However, the underlying mechanism remains unclear. We immunohistochemically analyzed pancreatic specimens from three individuals with ICI-related T1D, and their histopathological data were compared those from three patients who had received ICI therapy but did not develop T1D (non-T1D) and seven normal glucose-tolerant subjects as control subjects.

Anticancer maintenance chemotherapy prolonged prognosis of metastatic urothelial carcinoma patients: A single institute retrospective study using propensity score matching.

Objectives: To evaluate the therapeutic efficacy of anticancer maintenance chemotherapy for metastatic urothelial carcinoma.

Methods: We retrospectively compared the clinical outcomes of 74 patients with metastatic urothelial carcinoma who had been treated with or without anticancer maintenance chemotherapy between 2006 and 2020 at Osaka University Hospital. Progression-free survival and cancer-specific survival periods were calculated using the Kaplan-Meier method starting from the end date of induction chemotherapy.

EphA2 on urinary extracellular vesicles as a novel biomarker for bladder cancer diagnosis and its effect on the invasiveness of bladder cancer.

Background: Urinary extracellular vesicles (uEVs) secreted from bladder cancer contain cancer-specific proteins that are potential diagnostic biomarkers. We identified and evaluated a uEV-based protein biomarker for bladder cancer diagnosis and analysed its functions.

Methods: Biomarker candidates, selected by shotgun proteomics, were validated using targeted proteomics of uEVs obtained from 49 patients with and 48 individuals without bladder cancer, including patients with non-malignant haematuria.

Urine Cell-Free MicroRNAs in Localized Prostate Cancer Patients.

Prostate cancer (PCa) is the most common cancer in men. Prostate-specific antigen screening is recommended for the detection of PCa. However, its specificity is limited.

Circulating extracellular vesicles carrying Firmicutes reflective of the local immune status may predict clinical response to pembrolizumab in urothelial carcinoma patients.

Bacterial flora has clinical significance for the host. The metabolic environment created by this flora influences immunotherapy in urothelial carcinoma. However, there are no reports on the clinical significance of bacterial flora in the host bloodstream.

Biological distinction between grades 2 and 3 with respect to intravesical recurrence in T1 high-grade bladder tumors: a retrospective study.

Background: The pathological grading system for non-muscle-invasive bladder cancer is based on the WHO 2004/2016 classification system (low-grade: LG/high-grade: HG) and the WHO 1973 classification system (Grade 1: G1/Grade 2: G2/Grade 3: G3). Recently, the usefulness of combining both systems and classifying the tumors as LG/G1, LG/G2, HG/G2, and HG/G3 has been demonstrated. In this study, we compared the prognosis of intravesical recurrence in relation to different treatment intensities between HG/G2 and HG/G3 bladder cancers.

Perioperative circulating tumor DNA enables the identification of patients with poor prognosis in upper tract urothelial carcinoma.

Perioperative systemic chemotherapy improves the prognosis of upper tract urothelial carcinoma (UTUC). The first objective of this study was to verify whether perioperative circulating tumor DNA (ctDNA) analysis using a pan-cancer gene panel and next-generation sequencing could identify patients with poor prognosis who require perioperative chemotherapy. Second, we investigated whether ctDNA is useful for minimal residual disease (MRD) detection and treatment monitoring in UTUC.

Early dynamics of circulating tumor DNA predict clinical response to immune checkpoint inhibitors in metastatic renal cell carcinoma.

Objectives: Detection of genomic alterations in circulating tumor deoxyribonucleic acid of peripheral blood can guide the selection of systemic therapy in cancer patients. The predictive significance of circulating tumor deoxyribonucleic acid in metastatic renal cell carcinoma remains unclear, especially for patients treated with immune checkpoint inhibitors.

Methods: In this study, we collected plasma samples before and 1 month after commencing nivolumab monotherapy or nivolumab plus ipilimumab therapy from 14 metastatic renal cell carcinoma patients.

Gut Microbiota-Derived Short-Chain Fatty Acids Promote Prostate Cancer Growth via IGF1 Signaling.

Excessive intake of animal fat and resultant obesity are major risk factors for prostate cancer. Because the composition of the gut microbiota is known to change with dietary composition and body type, we used prostate-specific knockout mice as a prostate cancer model to investigate whether there is a gut microbiota-mediated connection between animal fat intake and prostate cancer. Oral administration of an antibiotic mixture (Abx) in prostate cancer-bearing mice fed a high-fat diet containing a large proportion of lard drastically altered the composition of the gut microbiota including and , inhibited prostate cancer cell proliferation, and reduced prostate expression and circulating insulin-like growth factor-1 (IGF1) levels.

Proteomic analysis of urinary and tissue-exudative extracellular vesicles to discover novel bladder cancer biomarkers.

Proteomic analysis of urinary extracellular vesicles (EVs) is a powerful approach to discover potential bladder cancer (BCa) biomarkers, however urine contains numerous EVs derived from the kidney and normal urothelial epithelium, which can obfuscate information related to BCa cell-derived EVs. In this study, we combined proteomic analysis of urinary EVs and tissue-exudative EVs (Te-EVs), which were isolated from culture medium of freshly resected viable BCa tissues. Urinary EVs were isolated from urine samples of 11 individuals (7 BCa patients and 4 healthy individuals), and Te-EVs were isolated from 7 BCa tissues.

Peripheral T cell receptor repertoire features predict durable responses to anti-PD-1 inhibitor monotherapy in advanced renal cell carcinoma.

Immune checkpoint inhibitors (ICIs) offer significant clinical benefits to a subset of cancer patients via the induction of a systemic T cell-mediated anti-cancer immune response. Thus, the dynamic characterization of T cell repertoires in the peripheral blood has the potential to demonstrate noninvasive predictive biomarkers for the clinical efficacy of ICIs. In this study, we collected tumor tissues and peripheral blood samples from 25 patients with advanced kidney cancer before anti-programmed cell death protein 1 (PD-1) treatment and 1, 3, and 6 months after treatment initiation.

Fragmentation of cell-free DNA is induced by upper-tract urothelial carcinoma-associated systemic inflammation.

Reliable biomarkers for upper-tract urothelial carcinoma (UTUC) have yet to be found. Plasma cell-free DNA (cfDNA) has been clinically applied as a minimally invasive blood biomarker for various types of cancer. We investigated the utility of plasma cfDNA as a blood biomarker in UTUC patients.

A Potential Mechanism of Anticancer Immune Response Coincident With Immune-related Adverse Events in Patients With Renal Cell Carcinoma.

Background/aim: Some reports showed encouraging efficacy of immune checkpoint inhibitors among patients who experienced immune-related adverse events (irAEs). Thus, characterization of T-cell repertoire and immune signatures in peripheral blood mononuclear cells (PBMCs) and tumors before and after immune checkpoint inhibitors treatment should contribute to better understanding of irAE-provoked anticancer immune responses.

Materials And Methods: We applied expression analysis of immune-related genes and T-cell receptor sequencing in tumor and PBMCs from five patients with renal cell carcinoma before combined immunotherapy and at the onset of severe irAEs.

Failure to achieve castrate level of serum testosterone during luteinizing hormone-releasing hormone agonist therapy in a patient with prostate cancer.

We report the failure to achieve castrate level of serum testosterone during luteinizing hormone-releasing hormone agonist therapy in a patient with prostate cancer. A 76-year-old man was admitted to our hospital for evaluation of an elevated serum prostate specific antigen (PSA) level (191.10 ng/ml) in August 2011.

TERT C228T mutation in non-malignant bladder urothelium is associated with intravesical recurrence for patients with non-muscle invasive bladder cancer.

Telomerase reverse transcriptase (TERT) promoter mutations are frequently found in tumors or urine from patients with urothelial carcinoma (UC). TERT promoter mutations are also detected in urine from patients with no evidence of cancer but are associated with subsequent UC development. Mutations in the TERT promoter are thought to be present in nonmalignant urothelium (NMU) during early stages of tumor formation prior to pathological change, but this has not been proven directly.

Clinical Significance of Hotspot Mutation Analysis of Urinary Cell-Free DNA in Urothelial Bladder Cancer.

Recent studies showed the clinical utility of next-generation sequencing of urinary cell-free DNA (cfDNA) from patients with urothelial bladder cancer (UBC). In this study, we aimed to develop urinary cfDNA analysis by droplet digital PCR (ddPCR) as a high-throughput and rapid assay for UBC detection and prognosis. We analyzed urinary cfDNA of 202 samples from 2 cohorts.

MicroRNA-92b-3p is a prognostic oncomiR that targets TSC1 in clear cell renal cell carcinoma.

Although several studies have reported that microRNA (miR)-92b-3p is involved in various cellular processes related to carcinogenesis, its physiological role in clear cell renal cell carcinoma (ccRCC) remains unclear. To clarify the role of miR-92b-3p in ccRCC, we compared miR-92b-3p expression levels in ccRCC tissues and adjacent normal renal tissues. Significant upregulation of miR-92b-3p was observed in ccRCC tissues.

The role of actinin-4 (ACTN4) in exosomes as a potential novel therapeutic target in castration-resistant prostate cancer.

Prostate cancer is the second leading cause of cancer death in men in the United States. Several novel therapeutic agents have been developed for castration-resistant prostate cancer (CRPC), but the prognosis for patients with CRPC remains poor. The identification of novel therapeutic targets for CRPC is an urgent issue.

[A Case of Urethral Carcinoma in Situ Resected by Urethrectomy of Anterior Urethra].

A 62-year-old man had been treated for urethral stricture developed after his right kidney was harvested for donation to his sister 34 years ago. Transurethral biopsy was performed because of positive urinary cytology and squamous cell carcinoma was detected from the site of urethral stricture. The patient with the desire to preserve the penis was referred to our department.

[A Case Report : Primary Urothelial Carcinoma of the Prostate Producing Interleukin-6 Detected from a Fever].

A 72-year-old man visited a hospital because of a fever and fatigue. His fever persisted and computed tomography revealed a tumor of the prostate. The patient was referred to our hospital with a suspicion of prostate cancer.