Nathan A. Bockholt

Ureteric stent placement with extraction string: no strings attached?

Study Type – Therapy (case series)

Anti-Interleukin-10R1 Monoclonal Antibody Enhances Bacillus Calmette-Guérin Induced T-Helper Type 1 Immune Responses and Antitumor Immunity in a Mouse Orthotopic Model of Bladder Cancer

PURPOSE Proper induction of the T-helper type 1 immune response is required for effective bacillus Calmette-Guérin immunotherapy for bladder cancer. Interleukin-10 down-regulates the T-helper 1 response and is associated with bacillus Calmette-Guérin failure. We investigated whether blocking interleukin-10 receptor 1 would enhance the bacillus Calmette-Guérin induced T-helper type 1 immune response and anti-bladder cancer immunity in a mouse model. MATERIALS AND METHODS Splenocytes were incubated with bacillus Calmette-Guérin or bacillus Calmette-Guérin plus control IgG1, anti-interleukin-10 receptor 1 mAb or anti-interleukin-10 neutralizing mAb, followed by enzyme-linked immunosorbent assay of interferon-γ production. Bladder RNA was extracted after intravesical bacillus Calmette-Guérin plus intraperitoneal IgG1 or anti-interleukin-10 receptor 1 mAb and analyzed by reverse transcriptase and/or quantitative polymerase chain reaction. Urine was collected and analyzed by enzyme-linked immunosorbent assay. Mice bearing a luciferase expressing MB49 orthotopic tumor were treated with intravesical bacillus Calmette-Guérin plus intraperitoneal IgG1 or anti-interleukin-10 receptor 1 mAb. Tumor response was assessed by bioluminescent imaging and bladder weight measurement. RESULTS Bacillus Calmette-Guérin plus anti-interleukin-10R1 mAb induced significantly higher interferon-γ production by splenocytes than bacillus Calmette-Guérin plus anti-interleukin-10 mAb. Bacillus Calmette-Guérin plus anti-interleukin-10 receptor 1 mAb also induced significantly higher interferon-γ mRNA and protein in bladder and urine, respectively, in a dose dependent manner. Treatment with phosphate buffered saline, bacillus Calmette-Guérin plus control IgG1 and bacillus Calmette-Guérin plus anti-interleukin-10 receptor 1 mAb showed a 0% tumor-free rate with a 20% death rate, a 20% tumor-free rate with a 20% death rate and a 40% tumor-free rate with a 0% death rate, respectively. Bladder weight also revealed the effect of anti-interleukin-10 receptor 1 mAb on the bacillus Calmette-Guérin induced bladder tumor response. CONCLUSIONS Anti-interleukin-10 receptor 1 mAb enhanced the bacillus Calmette-Guérin induced T-helper type 1 immune response and anti-bladder cancer immunity. A humanized form of this mAb warrants future investigation for bacillus Calmette-Guérin treatment of bladder cancer.

Giant Renal Angiomyolipoma without Fat Density on CT Scan: Case Report and Review of the Literature

Giant renal angiomyolipomas have been reported, but typically have the pathognomonic finding of fat density on CT scan. We present the case of a 53-year-old male with a symptomatic, 35-cm, predominantly cystic renal mass without fat density on CT that on nephrectomy was found to be a fat-poor angiomyolipoma with predominantly epithelioid morphology weighing 17.9 kg. Giant renal angiomyolipoma without macroscopic fat density on CT scan is an exceedingly rare occurrence.

Traumatic Urethral Injury without Pelvic Fracture in an Adult Female

A 23-year-old female was involved in a motor vehicle collision with multiple injuries, including a right acetabular fracture, but no pelvic fracture. Urology consultation was obtained due to difficulty placing a urethral catheter. Examination revealed a longitudinal urethral tear with vaginal laceration extending 2 cm from the urethral meatus proximally toward the bladder neck. The longitudinal urethral tear was repaired primarily. Traumatic female urethral injury in the absence of a pelvic fracture is an exceedingly rare occurrence.

Basal Cell Carcinoma of the Penis: A Case Report and Review of the Literature

Basal cell carcinoma of the penis is an extremely rare entity, accounting for less than 0.03% of all basal cell carcinomas. Fortunately, wide local excision of such lesions is generally curative. Fewer than 25 cases have been reported in the literature describing penile basal cell carcinoma. Here we report a case of penile basal cell carcinoma cured with wide local excision.

Transitional Cell Carcinoma within a Portion of Inguinally Herniated Bladder.

Bladder herniation within the inguinal canal is a relatively uncommon finding. We report an even less-common occurrence of transitional cell carcinoma located within a portion of inguinally herniated bladder. Fewer than 20 reports exist in the literature describing this scenario.

877 ANTI-IL10-R1 MONOCLONAL ANTIBODY ENHANCES BACILLUS CALMETTE-GUERIN (BCG) INDUCED TH1 AND ANTI-BLADDER CANCER IMMUNE RESPONSES IN VITRO AND IN VIVO

nodal stage, they are associated with inferior disease outcomes. Detection of even 1 CTC/7.5 mL blood in UCB patients prior to RC is an independent predictor for disease recurrence and cancer-related death. These findings are very important for future investigations, as they are in contradiction to theories supporting a cut-off value of 5 or more CTC needed for accurate outcome prediction. Therefore, CTC may represent a feasible biomarker for monitoring response to neoadjuvant and adjuvant chemotherapy.

Abstract 5390: Anti-IL10-R1 monoclonal antibody with concomitant bacillus calmette-Guérin (BCG) prevents metastatic bladder cancer in an in vivo mouse model

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Introduction: Induction of Th1 immunity is required for effective intravesical BCG immunotherapy of bladder cancer. IL-10 down-regulates the Th1 response and is associated with BCG failure. We previously demonstrated that blocking IL-10 receptor (IL-10R) by systemic administration of anti-IL-10R1 mAb enhanced intravesical BCG (living Pasteur strain) treatment of bladder cancer in an orthotopic mouse model. Here we investigated the effect of anti-IL-10R1 mAb on clinically used BCG (lyophilized TICE strain) for induction of anti-bladder cancer immunity. Methods: Splenocytes were incubated with BCG alone or plus control IgG or ant-IL-10R1 mAb for 24 hours, followed by ELISA analysis of IFN-γ production. Bladder RNA was extracted after 6 treatments (twice weekly) with intravesical (i.b.) BCG plus intraperitoneal (i.p.) control IgG or anti-IL-10R1 mAb, followed by qPCR analysis of IFN-γ mRNA expression. Three groups of 20 mice were inoculated with luciferase-expressing MB49 bladder cancer cells and treated with i.b. PBS plus i.p. PBS (Group 1), i.b. BCG plus i.p. control IgG (Group 2), or i.b. BCG plus i.p. anti-IL-10R1 mAb (Group 3) 2x/wk for 6 total treatments. Mice were monitored weekly using IVIS luminescence and followed for 76 days. A bioluminesence cutoff of 5X104 p/s was used to establish the presence of bladder cancer. At animal death bladders were collected, weighed and processed for histological analysis. In suspected cases of metastatic disease the affected organs were also collected for histological analysis. Results: BCG plus anti-IL-10R1 mAb induced increased IFN-γ production by splenocytes in a dose-dependent manner. BCG plus anti-IL-10R1 mAb substantially increased IFN-γ mRNA. Eleven, 17 and 9 mice from Groups 1, 2 and 3, respectively, developed bladder cancer. One mouse in Group 2 and 2 mice in Group 3 showed cancer regression. 36%, 53% and 0% of Groups 1, 2 and 3 developed metastatic bladder cancer, respectively (p=0.020). While bladder weights for the groups were different, the differences did not reach statistical significance. Conclusions: Anti-IL-10R1 mAb enhances BCG-induced Th1 immune responses both in vitro and in vivo. Intravesical BCG plus anti-IL-10R1 mAb shows statistical significance in preventing metastasis of bladder cancer in an orthotopic bladder tumor mouse model. Anti-IL-10R1 mAb may prove useful in clinical practice for the prevention of metastatic bladder cancer in high-risk patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5390. doi:1538-7445.AM2012-5390