Background: For selected locally advanced prostate cancer (PCa) patients, radical prostatectomy (RP) is one of the first-line treatments. We aimed to develop a preoperative nomogram to identify what kinds of patients can get the most survival benefits after RP. Methods: We conducted analyses with data from the Surveillance, Epidemiology, and End Results (SEER) database. Covariates used for analyses included age at diagnosis, marital status, race, American Joint Committee on Cancer (AJCC) 7th TNM stage, Prostate specific antigen, Gleason biopsy score (GS), percent of positive cores. We estimated the cumulative incidence function for cause-specific death. The Fine and Gray's proportional subdistribution hazard approach was used to perform multivariable competing risk analyses and reveal prognostic factors. A nomogram was built by these factors (including GS, percent of positive cores and N stage) and validated by concordance index and calibration curves. Risk stratification was established based on the nomogram. Results: We studied 14,185 patients. N stage, GS, and percent of positive cores were the independent prognostic factors used to construct the nomogram. For validating, in the training cohort, the C-index was 0.779 (95% CI 0.736-0.822), and in the validation cohort, the C-index was 0.773 (95% CI 0.710-0.836). Calibration curves showed that the predicted survival and actual survival were very close. The nomogram performed better over the AJCC staging system (C-index 0.779 versus 0.764 for training cohort, and 0.773 versus 0.744 for validation cohort). The new stratification of risk groups based on the nomogram also showed better discrimination than the AJCC staging system. Conclusions: The preoperative nomogram can provide favorable prognosis stratification ability to help clinicians identify patients who are suitable for surgery.

Cancer associated fibroblasts (CAFs) support tumors via multiple mechanisms, including maintaining the immunosuppressive tumor microenvironment and limiting infiltration of immune cells. The prolyl isomerase Pin1, whose overexpression in CAFs has not been fully profiled yet, plays critical roles in tumor initiation and progression. To decipher effects of selective Pin1 inhibition in CAFs on pancreatic cancer, here we formulate a DNA-barcoded micellular system (DMS) encapsulating the Pin1 inhibitor AG17724. DMS functionalized with CAF-targeting anti-FAP-α antibodies (antiCAFs-DMS) can selectively inhibit Pin1 in CAFs, leading to efficacious but transient tumor growth inhibition. We further integrate DNA aptamers (AptT), which can engage CD8+ T lymphocytes, to obtain a bispecific antiCAFs-DMS-AptT system. AntiCAFs-DMS-AptT inhibits tumor growth in subcutaneous and orthotopic pancreatic cancer models.

Background: For selected locally advanced prostate cancer (PCa) patients, radical prostatectomy (RP) is one of the first-line treatments. We aimed to develop a preoperative nomogram to identify what kinds of patients can get the most survival benefits after RP. Methods: We conducted analyses with data from the the Surveillance, Epidemiology, and End Results (SEER) database. Univariable and multivariable Cox regression analyses were used to reveal prognostic factors. A nomogram was built by these factors and validated by concordance index (C-index) and calibration curves. Risk stratification was established based on the nomogram. Results: We studied 14185 patients. N stage, Gleason Score, and percent of positive cores were the independent prognostic factors used to construct the nomogram. For validating, in the training cohort, the C-index was 0.779 (95% CI 0.736–0.822), and in the validation cohort, the C-index was 0.773 (95% CI 0.718–0.808). Calibration curves showed that the predicted survival and actual survival were very close. The nomogram performed better over the American Joint Committee on Cancer (AJCC) staging system (C-index 0.779 versus 0.763 for training cohort, and 0.773 versus 0.745 for validation cohort). The new stratification of risk groups based on the nomogram also showed better discrimination than the AJCC staging system. Conclusions: The preoperative nomogram can provide favorable prognosis stratification ability to help clinicians identify patients who are suitable for surgery.

Background: For selected locally advanced prostate cancer (PCa) patients, radical prostatectomy (RP) is one of the first-line treatments. We aimed to develop a preoperative nomogram to identify what kinds of patients can get the most survival benefits after RP. Methods: We conducted analyses with data from the Surveillance, Epidemiology, and End Results (SEER) database. Covariates used for analyses included age at diagnosis, marital status, race, American Joint Committee on Cancer (AJCC) 7th TNM stage, Prostate specific antigen, Gleason biopsy score (GS), percent of positive cores. We estimated the cumulative incidence function for cause-specific death. The Fine and Gray’s proportional subdistribution hazard approach was used to perform multivariable competing risk analyses and reveal prognostic factors. A nomogram was built by these factors (including GS, percent of positive cores and N stage) and validated by concordance index and calibration curves . Risk stratification was established based on the nomogram. Results: We studied 14185 patients. N stage, GS, and percent of positive cores were the independent prognostic factors used to construct the nomogram. For validating, in the training cohort, the C-index was 0.779 (95% CI 0.736–0.822), and in the validation cohort, the C-index was 0.773 (95% CI 0.710–0.836). Calibration curves showed that the predicted survival and actual survival were very close. The nomogram performed better over the AJCC staging system (C-index 0.779 versus 0.764 for training cohort, and 0.773 versus 0.744 for validation cohort). The new stratification of risk groups based on the nomogram also showed better discrimination than the AJCC staging system. Conclusions: The preoperative nomogram can provide favorable prognosis stratification ability to help clinicians identify patients who are suitable for surgery.