Showing papers by "Weilin Hou published in 2022"

Negative Effects of Stromal Neutrophils on T Cells Reduce Survival in Resectable Urothelial Carcinoma of the Bladder

Abstract: Urothelial carcinoma of the bladder (UCB) is a major type of bladder cancer with a distinct tumor microenvironment (TME). Although neutrophils are the main component of myeloid cells in the TME, the clinical significance and function of the neutrophils remain unclear in UCB. Here, we observed CD66b+ neutrophils were predominantly enriched in the stroma of UCB tissues and their levels emerged as an independent prognostic factor for overall survival (P = 0.006, n = 237), and were positively associated with age (P = 0.033), tumor stage (P < 0.0001), nodal metastasis (P = 0.045), and histological grade (P < 0.0001). Furthermore, we found that CD66b+ neutrophils were frequently co-localized with CD4+ T cells (R=0.35, P = 0.0067), CD8+ T cells (R=0.52, P<0.0001) and Cleaved Caspase-3+ apoptosis cells (R=0.44, P = 0.0007) in the stroma of UCB tissue. In addition, better effects of T cells on patients’ survival were markedly reduced by neutrophils and T cells co-infiltration. Moreover, we confirmed bladder tumor cell supernatant treated neutrophils suppressed T cell proliferation and activation, and promoted T cell apoptosis through GM-CSF induced PD-L1 in vitro. The expression of PD-L1 by neutrophils was also detected in fresh UCB tissues by using flow cytometric analysis. These data suggested that stromal CD66b+ neutrophils may potentially represent a reliable marker of poor prognosis for UCB patients, and neutrophils might play an immunosuppressive role on T cell immunity partially via the expression of PD-L1.

Targeting treatment of bladder cancer using PTK7 aptamer-gemcitabine conjugate

Abstract: Abstract Background Gemcitabine (GEM) is one of the first-line chemotherapies for bladder cancer (BC), but the GEMs cannot recognize cancer cells and have a low long-term response rate and high recurrence rate with side effects during the treatment of BC. Targeted transport of GEMs to mediate cytotoxicity to tumor and avoid the systemic side effects remains a challenge in the treatment of BC. Methods Based on a firstly confirmed biomarker in BC-protein tyrosine kinase 7 (PTK7), which is overexpressed on the cell membrane surface in BC cells, a novel targeting system protein tyrosine kinase 7 aptamer-Gemcitabine conjugate (PTK7-GEMs) was designed and synthesized using a specific PTK7 aptamer and GEM through auto-synthesis method to deliver GEM against BC. In addition, the antitumor effects and safety evaluation of PTK7-GEMs was assessed with a series of in vitro and in vivo assays. Results PTK7-GEMs can specifically bind and enter to BC cells dependent on the expression levels of PTK7 and via the macropinocytosis pathway, which induced cytotoxicity after GEM cleavage from PTK7-GEMs respond to the intracellular phosphatase. Moreover, PTK7-GEMs showed stronger anti-tumor efficacy and excellent biosafety in three types of tumor xenograft mice models. Conclusion These results demonstrated that PTK7-GEMs is a successful targeted aptamer-drug conjugates strategy (APDCs) to treat BC, which will provide new directions for the precision treatment of BC in the field of biomarker-oriented tumor targeted therapy.

“Light green up”: Indocyanine Green Fluorescence Imaging–guided Robotic Bilateral Inguinal Lymphadenectomy by the Hypogastric Subcutaneous Approach for Penile Cancer

Abstract: Inguinal lymphadenectomy is of great significance in the management of penile cancer, which aims to mitigate the progression of lymph node metastasis. It is important to improve the efficiency of lymph node dissection and reduce surgical complications.To detail a novel technique for robotic bilateral inguinal lymphadenectomy through the hypogastric subcutaneous approach by indocyanine green (ICG) fluorescence imaging, which promotes the identification and dissection of inguinal lymph nodes with considerable safety.Ten eligible penile cancer patients who underwent ICG fluorescence imaging-guided robotic bilateral inguinal lymphadenectomy were prospectively enrolled (ICG group). Sixteen patients who underwent the surgery without ICG were retrospectively set as the control (non-ICG) group. Follow-up records for at least 12 mo were required.Inguinal lymphadenectomy was performed by the hypogastric subcutaneous approach. The ICG solution was subcutaneously injected into the prepuce at the beginning of surgery, and ICG fluorescence imaging-guided robotic-assisted bilateral inguinal lymphadenectomy was conducted.Clinical outcomes were collected. The primary study outcome measurement was the number of dissected inguinal lymph nodes.The numbers of inguinal overall, superficial, and deep lymph nodes retrieved were all higher in the ICG than in the non-ICG group (p < 0.05). No patients had severe perioperative complications. No difference was found in the overall complication rate and 12-mo survival between two groups (p > 0.05).ICG fluorescence imaging-guided robotic inguinal lymphadenectomy via the hypogastric subcutaneous approach is feasible and safe for patients with penile cancer, which is beneficial for dissecting more inguinal lymph nodes with few surgical complications.We developed a promising indocyanine green fluorescence imaging-guided technique to perform robotic bilateral inguinal lymphadenectomy on patients with penile cancer, which conduces to remove more inguinal lymph nodes with limited complications.

Single-site multiport vs. conventional multiport robot-assisted radical prostatectomy: A propensity score matching comparative study

Abstract: Objective Robot-assisted radical prostatectomy (RARP) is a dynamically evolving technique with its new evolution of single-site RARP. Here we sought to describe our extraperitoneal technique, named the single-site multiport RARP (ssmpRARP) using the da Vinci Si® platform and compare it with the transperitoneal conventional multiport RARP (cmpRARP). Materials and Methods Data were retrospectively collected for patients who underwent RARP for localized prostate cancer from June 2020 to January 2022 in a single center. Propensity score matching was performed based on age, prostate size, body mass index, neoadjuvant hormonal therapy usage, prostate-specific antigen levels, and clinical T stage. The differences between the matched two groups were investigated. Results Of the patients, 20 underwent ssmpRARP and 42 underwent cmpRARP during the period. After matching, 18 patients from each group were selected. Median follow-up was 7.8 months (2–12 months) for the ssmpRARP group, and 15.0 months (3–26 months) for cmpRARP. The demographic features between the two groups were comparable. The median total operative time, estimated blood loss, pathologic data, early follow-up outcomes, and hospitalization stays and costs were similar between the two groups. The ssmpRARP group tended to return to their bowel activities earlier (44.78 ± 10.83 h vs. 54.89 ± 12.97 h, p = 0.016). There were no significant differences in complication rates. Conclusions We demonstrated the feasibility and safety of performing extraperitoneal ssmpRARP using the da Vinci Si® robotic platform. Our technique showed comparable short-term outcomes with the transperitoneal cmpRARP. Prospective trials and long-term follow-up are necessary to confirm these results.