Human kallikrein peptidase 2 (hK2) is a prostate specific enzyme whose expression is governed by the androgen receptor (AR). AR is the central oncogenic driver of prostate cancer (PCa) and is also a key regulator of DNA repair in cancer. We report an innovative therapeutic strategy that exploits the hormone-DNA repair circuit to enable molecularly-specific alpha particle irradiation of PCa. Alpha-particle irradiation of PCa is prompted by molecularly specific-targeting and internalization of the humanized monoclonal antibody hu11B6 targeting hK2 and further accelerated by inherent DNA-repair that up-regulate hK2 (KLK2) expression in vivo. hu11B6 demonstrates exquisite targeting specificity for KLK2. A single administration of actinium-225 labeled hu11B6 eradicates disease and significantly prolongs survival in animal models. DNA damage arising from alpha particle irradiation induces AR and subsequently KLK2, generating a unique feed-forward mechanism, which increases binding of hu11B6. Imaging data in nonhuman primates support the possibility of utilizing hu11B6 in man.
Tumors that showed a vesicular staining pattern of legumain had the potential of being highly invasive and aggressive in patients with prostate cancer who were treated with radical prostatectomy. This suggests that legumain might contribute to the invasiveness and aggressiveness of prostate cancer.
Tumor size 7 cm or less, age 60 years or greater and a decreased preoperative glomerular filtration rate were significant risk factors for new onset renal insufficiency in patients treated with radical nephrectomy. Partial nephrectomy might be considered an option according to the risk of postoperative renal insufficiency, especially in elderly patients with a tumor of 7 cm or less.
Preoperative NLR elevation is significantly associated with poor outcomes in patients with metastatic RCC who underwent CN. Patients with NLR ≥4.0 and ECOG-PS ≥ 1 might not benefit from immediate CN after initial diagnosis.
Objective: In Japan, no study has compared the perioperative outcomes observed between robot-assisted radical cystectomy (RARC) and open radical cystectomy (ORC). This study aimed at a prospective comparison of the perioperative outcomes between RARC and ORC performed by a single surgeon. Methods: Between 2008 and 2011, 26 bladder cancer patients underwent radical cystectomy by one surgeon, 11 robotically and 15 by open procedure. We prospectively collected perioperative and pathological data for these 26 patients, and retrospectively compared these two different surgical procedures. Results: The RARC cohort had a significant decrease in both estimated blood loss (656.9 vs. 1788.7 ml, P ¼ 0.0015) and allogeneic transfusion requirement (0 vs. 40%, P ¼ 0.0237). The total operative time was almost the same (P ¼ 0.2306) but increased duration of bladder removal and lymphadenectomy was observed in the RARC cohort (P ¼ 0.0049). Surgeryrelated complication rates within 30 days were not significantly different (P ¼ 0.4185). Positive surgical margin was observed in three patients in the ORC cohort and in one patient in the RARC cohort (P ¼ 0.4664). The RARC cohort had a larger number of removed lymph nodes than the ORC cohort, and the difference was statistically significant (20.7 vs. 13.8, P ¼ 0.0421). Conclusions: We confirmed that RARC is safe and yields acceptable outcomes in comparison with ORC for the treatment of bladder cancer if it is performed by a surgeon who has experience of over 60 cases of robot-assisted radical prostatectomy. It is hoped that RARC will gain acceptance in Japan as a minimally invasive surgery for muscle-invasive bladder cancer.
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