This study investigated tumor-associated macrophages activity in the microenvironment of renal cell carcinoma. Via a co-culture with macrophage-like cells differentiated from human monocyte cell line THP-1 and U937 cells, the migration ability of ACHN and Caki-1 cells, which are human renal cell carcinoma cell line cells, was significantly increased, as was the epithelial–mesenchymal transition change. A chemokine array identified the CCL20-CCR6 axis as a concentration-dependent signal in ACHN and Caki-1 cell migration. Akt in the ACHN and Caki-1 cells was activated by macrophage-like cells, and the CCL20 neutralizing antibody suppressed migration ability, epithelial–mesenchymal transition, and Akt phosphorylation in the ACHN and Caki-1 cells. Akt inhibitor AZD5363 also decreased the epithelial–mesenchymal transition change and migration ability in the ACHN and Caki-1 cells. In 42 renal cell carcinoma tissues, patients with CCR6 and macrophage infiltration indicated poor prognoses. In the tumor microenvironment of renal cell carcinoma, cancer cells are activated by CCL20 secreted by tumor-associated macrophages through Akt activation, followed by epithelial–mesenchymal transition and an acquired migration ability. Thus, inhibition of the CCL20-CCR6 axis may be a potential therapeutic strategy for renal cell carcinoma.
During radical prostatectomy, the prostate is removed along with the seminal vesicles, and the urinary tract is reconstructed by dropping the bladder onto the pelvic floor and suturing the bladder and urethra together. This process causes damage to the pelvic floor and postoperative complications due to the anatomical changes in the pelvic floor caused by the vesicourethral anastomosis. Urinary incontinence and erectile dysfunction are major complications that impair patients’ quality of life after radical prostatectomy. In addition, the shortening of the penis and the increased prevalence of inguinal hernia have been reported. Since these postoperative complications subsequently affect patients’ quality of life, their reduction is a matter of great interest, and procedural innovations such as nerve-sparing techniques, Retzius space preservation, and inguinal hernia prophylaxis have been developed. It is clear that nerve sparing is useful for preserving the erectile function, and nerve sparing, urethral length preservation, and Retzius sparing are useful for urinary continence. The evaluation of pre- and postoperative imaging to observe changes in pelvic anatomy is also beginning to clarify why these techniques are useful. Changes in pelvic anatomy after radical prostatectomy are inevitable and, therefore, postoperative complications cannot be completely eliminated; however, preserving as much of the tissue and structure around the prostate as possible, to the extent that prostate cancer control is not compromised, may help reduce the prevalence of postoperative complications.
The suppression of androgen receptor (AR) expression exacerbates the migration potential of prostate cancer. This study identified a previously unrecognized regulation of the AR‐controlled pathway that promotes migration potential in prostate cancer cells. Prostate cancer cells that pass through a transwell membrane (mig cells) have a higher migration potential with a decreased AR expression than parental cells. In this study, we aimed to elucidate the mechanism of migration enhancement associated with the suppression of AR signaling. Expression of C–C motif ligand 20 (CCL20) is upregulated in mig cells, unlike in the parental cells. Knockdown of AR with small interfering RNA (siAR) in LNCaP and C4‐2B cells increased CCL20 secretion and enhanced the migration of cancer cells. Mig cells, CCL20‐treated cells, and siAR cells promoted cell migration with an enhancement of AKT phosphorylation and Snail expression, while the addition of a C–C chemokine receptor 6 (CCR6, the specific receptor of CCL20) inhibitor, anti‐CCL20 antibody, and AKT inhibitor suppressed the activation of AKT and Snail. With 59 samples of prostate cancer tissue, CCL20 secretion was profuse in metastatic cases despite low AR expression levels. Snail expression was associated with the expression of CCL20 and CCR6. A xenograft study showed that the anti‐CCL20 antibody significantly inhibited Snail expression, thereby suggesting a new therapeutic approach for castration‐resistant prostate cancer with the inhibition of the axis between CCL20 and CCR6.
Advances in imaging technologies have increased the opportunities for treating small-diameter renal cell carcinomas (RCCs) in the elderly. This retrospective study based on real-world clinical practice compared perioperative complications, preoperative and postoperative renal function, recurrence-free survival, and overall survival in elderly patients with RCC who had undergone robot-assisted partial nephrectomy (RAPN) or percutaneous cryoablation (PCA). A total of 99 patients (aged ≥70 years), including 50 and 49 patients in the RAPN and PCA groups, respectively, were analyzed. In the entire cohort, Clavien–Dindo grade ≥3 complications occurred in only one patient who had undergone RAPN. Renal function was significantly lower in the postoperative period than in the preoperative period in both the RAPN and PCA groups. The recurrence-free survival and overall survival rates were worse in the PCA group than in the RAPN group, albeit not significantly. RAPN was considered a safe and effective method for treating RCCs in elderly patients. Moreover, although the recurrence rate was slightly higher in the PCA group than in the RAPN group, PCA was deemed to be a safe alternative, especially for treating patients in whom general anesthesia poses a high risk.
Background: The detection of microsatellite instability in urologic cancers is rare, especially in metastatic, castration-resistant prostate cancer with neuroendocrine differentiation.Case presentation: This is a case of a 66-year-old Asian male patient with prostate adenocarcinoma who had metastases at initial presentation. Despite combined androgen deprivation therapy, his prostate-specific antigen (PSA) progressively increased, and prostate re-biopsy revealed small cell carcinoma. He was treated with platinum-based systemic chemotherapy, and his tumor markers, including PSA, remained negative; however, his local symptoms worsened. Subsequently, microsatellite instability-high was detected, and pembrolizumab was administered resulting in complete remission with the resolution of symptoms and continued therapeutic effect for more than 14 months.Conclusion: Microsatellite instability testing should be considered, despite its low detection rate, because the response to pembrolizumab in metastatic, castration-resistant prostate cancer with detectable microsatellite instability is associated with a prolonged duration of response.