Comparative analysis of gut microbiota in hormone-sensitive and castration-resistant prostate cancer in Japanese men.

Gut microbiota plays a crucial role in the development and progression of prostate cancer, with previous studies indicating that certain bacterial taxa are more abundant in castration-resistant prostate cancer (CRPC) compared to hormone-sensitive prostate cancer (HSPC). Notably, the composition of gut microbiota can vary significantly by geographic region, and Japanese individuals have a distinct microbial profile. However, research exploring these differences within Japanese populations remains limited.

External beam radiotherapy combination is a risk factor for bladder cancer in patients with prostate cancer treated with brachytherapy.

Purpose: To investigate the risk of bladder cancer (BCa) in patients treated with brachytherapy for prostate cancer (PCa).

Methods: We retrospectively analyzed 583 patients with PCa who underwent brachytherapy with or without external beam radiotherapy (EBRT). We analyzed the disease-free survival (DFS) of BCa in patients with PCa who underwent brachytherapy with or without EBRT.

Immunohistochemical Analysis of HER2, EGFR, and Nectin-4 Expression in Upper Urinary Tract Urothelial Carcinoma.

Background/aim: Upper urinary tract urothelial carcinoma (UTUC) is a rare disease, often discovered at an advanced stage at diagnosis. Nectin-4 is expressed in a broad range of patients with UTUC and is associated with poor progression-free survival. The receptors of the erythroblastosis oncogene B (ErbB) family are potential therapeutic targets for urothelial carcinoma.

The Association of Tumor Immune Microenvironment of the Primary Lesion with Time to Metastasis in Patients with Renal Cell Carcinoma: A Retrospective Analysis.

Biological or immunological differences in primary lesions between synchronous and metachronous metastatic renal cell carcinoma (mRCC) have been reported. However, the association between the tumor immune microenvironment (TIME) of primary lesions and time to metastasis remains unknown. We investigated the differences in the TIME of primary lesions based on time intervals to metastasis, mainly between the synchronous group (SG; metastasis within 3 months) and metachronous group (MG; metastasis after 3 months), and its association with clinicopathological parameters in patients with mRCC.

Targeted-sequence of normal urothelium and tumor of patients with non-muscle invasive bladder cancer.

During tumorigenesis, certain tissues are colonized by mutant clones with oncogenic driver mutations as precancer lesions. These mutations can facilitate clonal expansion and may contribute to malignant transformation. The molecular features of low-grade non-muscle invasive bladder cancer (NMIBC) and high-grade bladder cancer are so distinct that they are thought to follow different evolutionary tumorigenesis pathways.

The pressure flow study investigation of pathophysiology of post-micturition dribble in male patients.

Purpose: In this study, we aimed to elucidate the pathophysiology of post-micturition dribble (PMD) through analyzing several variables including pressure flow study (PFS) findings and symptoms questionnaire.

Methods: We retrospectively analyzed male patients who visited our department between 2010 and 2020. We used modified international prostate symptom score (m-IPSS), which consists of eight sub-score related to lower urinary tract symptoms (Incomplete Emptying, Frequency, Intermittency, Urgency, Weak Stream, Straining, Nocturia, and PMD) and one question related to quality of life (QOL).

Prognostic factors in Japanese men with high-Gleason metastatic castration-resistant prostate cancer.

Background: Several therapeutic agents are available for metastatic castration-resistant prostate cancer (CRPC). However, prognosis is still not well developed. The Gleason score (GS) is a prognostic factor available for patients with metastatic CRPC.

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.

Gut microbiome and prostate cancer.

The gut microbiome is linked to several diseases such as Alzheimer's disease, rheumatoid arthritis, and colon cancer. The gut microbiome is also associated with the modulation of immune function, resulting in a different response to immune checkpoint therapy. The gut microbiome differs according to lifestyle, diet, sex, race, genetic background, and country.

Firmicutes in Gut Microbiota Correlate with Blood Testosterone Levels in Elderly Men.

Purpose: In males, testosterone levels have been implicated in various diseases. Recently, the influence of gut microbial-derived compounds on host metabolism has become evident, and it has been suggested that some gut bacteria may be involved in testosterone metabolism. In the present study, we examined the relationship between testosterone levels and gut microbiota in elderly Japanese men.

Context-Specific Efficacy of Apalutamide Therapy in Preclinical Models of -Deficient Prostate Cancer.

Significant improvements with apalutamide, a nonsteroidal antiandrogen used to treat patients suffering from advanced prostate cancer (PCa), have prompted evaluation for additional indications and therapeutic development with other agents; however, persistent androgen receptor (AR) signaling remains problematic. We used autochthonous mouse models of -deficient PCa to examine the context-specific antitumor activity of apalutamide and profile its molecular responses. Overall, apalutamide showed potent antitumor activity in both early-stage and late-stage models of castration-naïve prostate cancer (CNPC).

Higher neutrophil-to-lymphocyte ratio after the first cycle of the first-line chemotherapy is associated with poor cancer specific survival of upper urinary tract carcinoma patients.

Background: Inflammatory cytokines and immature myeloid derived suppressor cells (MDSCs), which increase during cancer progression, could lead to a neutrophil increase and lymphocyte reduction. Thus, the neutrophil-lymphocyte ratio (NLR) was used to predict survival of patients suffering from urological cancers including upper urinary tract carcinoma. We further determined whether the NLR during the first cycle of first-line chemotherapy could predict cancer specific survival.

Expression of Nectin-4 and PD-L1 in Upper Tract Urothelial Carcinoma.

Enfortumab vedotin is a novel antibody-drug conjugate targeting Nectin-4, which is highly expressed in urothelial carcinoma. However, the expression status of Nectin-4 in upper tract urothelial carcinoma (UTUC) remains unclear. The relationship between Nectin-4 and Programmed Death Ligand 1 (PD-L1) in UTUC is also ambiguous.

Clinical significance of Akt2 in advanced pancreatic cancer treated with erlotinib.

Akt2 is an isoform of Akt, and an association between Akt2 and resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has been suggested in pancreatic cancer (PC) in vitro. In this study, we investigated the association between Akt2 expression as evaluated using immunohistochemistry and the outcome of patients with advanced PC who had received treatment with erlotinib (an EGFR-TKI). Although the difference was not significant, patients with high levels of Akt2 expression tended to have a poorer response and a shorter progression-free survival period after treatment with erlotinib plus gemcitabine than those with low expression levels (P=0.

Case report: Durable response to afatinib in a patient with lung cancer harboring two uncommon mutations of EGFR and a KRAS mutation.

Comprehensive genomic profiling for non-small cell lung cancer (NSCLC) is likely to identify more patients with rare genetic alterations including uncommon epidermal growth factor receptor gene (EGFR) mutations. It remains unclear how such patients should be treated, however. We here report a case of NSCLC positive for two uncommon mutations of EGFR and a KRAS mutation, including its treatment with the second-generation EGFR tyrosine kinase inhibitor (TKI) afatinib.

MEK inhibitors against MET-amplified non-small cell lung cancer.

Several receptor tyrosine kinases (RTKs) including EGFR, ALK, and MET have been identified as therapeutic targets in non-small cell lung cancer (NSCLC). Among the downstream pathways of RTKs, the MAPK pathway is particularly important for cancer cell proliferation, differentiation, and survival. In this study, the effects of MEK inhibitors (trametinib and PD0325901) in several NSCLC cell lines with driver gene alterations, especially RTK genes, were tested in vitro using an MTT assay, and a wide range of sensitivities was found.

Sensitivities to various epidermal growth factor receptor-tyrosine kinase inhibitors of uncommon epidermal growth factor receptor mutations L861Q and S768I: What is the optimal epidermal growth factor receptor-tyrosine kinase inhibitor?

Most patients with non-small cell lung cancer (NSCLC) harboring common epidermal growth factor receptor (EGFR) mutations, such as deletions in exon 19 or the L858R mutation in exon 21, respond dramatically to EGFR tyrosine kinase inhibitors (EGFR-TKI), and their sensitivities to various EGFR-TKI have been well characterized. Our previous article showed the in vitro sensitivities of EGFR exon 18 mutations to EGFR-TKI, but little information regarding the sensitivities of other uncommon EGFR mutations is available. First, stable transfectant Ba/F3 cell lines harboring EGFR L858R (Ba/F3-L858R), L861Q (Ba/F3-L861Q) or S768I (Ba/F3-S768I) mutations were created and their drug sensitivities to various EGFR-TKI were examined.

Afatinib against Esophageal or Head-and-Neck Squamous Cell Carcinoma: Significance of Activating Oncogenic HER4 Mutations in HNSCC.

The prognosis for patients with advanced esophageal or head-and-neck squamous cell carcinoma (ESCC or HNSCC) remains poor, and the identification of additional oncogenes and their inhibitors is needed. In this study, we evaluated the sensitivities of several ESCC and HNSCC cell lines to HER inhibitors (cetuximab, erlotinib, and afatinib) in vitro and found two cell lines that were hypersensitive to afatinib. Sequence analyses for the afatinib-targeted HER family genes in the two cell lines revealed that one cell line had a previously reported activating EGFR L861Q mutation, whereas the other had an HER4 G1109C mutation of unknown function.