ABSTRACT
Although immunotherapy has revolutionized cancer treatment and achieved remarkable success across many different cancer types, only a subset of patients shows meaningful clinical responses. In particular, advanced prostate cancer exhibits overwhelming de novo resistance to immune checkpoint blockade therapy. This is primarily due to the immunosuppressive tumor microenvironment of prostate cancer. Therefore, it is paramount to understand how prostate cancer cell-intrinsic mechanisms promote immune evasion and foster an immunosuppressive microenvironment. Here, we review recent findings that reveal the roles of the genetic alterations, androgen receptor signaling, cancer cell plasticity, and oncogenic pathways in shaping the immunosuppressive microenvironment and thereby driving immunotherapy resistance. Based on preclinical and clinical observations, a variety of therapeutic strategies are being developed that may illuminate new paths to enhance immunotherapy efficacy in prostate cancer.
Subject(s)
Male , Humans , Prostatic Neoplasms/pathology , Prostate/pathology , Immunotherapy , Tumor MicroenvironmentABSTRACT
Objective To explore adaptability of the patellofemoral joint after combined soft-tissue surgery in treatment of habitual patellar dislocation at different age. Methods Seventy-three children with habitual patellar dislocation were retrospectively reviewed from 2000 to 2007. There were 24 males and 49 females, with a mean age of 7.1 years(ranged 3-15). The mean follow-up period was 38 months (ranged 25-98). There were 24 patients with 30 knees aged from 3 to 8 years in A group and 49 cases with 69 knees aged from 8 to 15 years in B group. The combined soft-tissue surgery procedure consists of lateral capsular release, medial retinacular tightening of the knee, vastus medialis muscle transfer to the patella, medial and distal transfer of the half patellar tendon. Patella axial and knee lateral X-ray examination were obtained.Femoral trochlear angle,patellar height changes, patellofemoral congruence angle and patellar tilt angle (Laurin angle) were measured to evaluate adaptability of the patellofemoral joint. Results The data of 73 cases were complete. At the last visit, no recurrence of patellar lateral dislocation was found and two cases had patella medial dislocation. Femoral trochlear angle improved from 150.1°±5.1° preoperatively to 144.3°±6.0° postoperatively (P ＜0.05) in A group, while similar changes had not found (P ＞ 0.05) in B group. There were no difference in A and B group in regard to patellar height, congruence angle and Laurin angle. Conclusion The combined soft-tissue surgery had effect on patellofemoral joint remodel in children with habitual patellar dislocation. These procedures can significantly promote development of the femoral condyle, decrease femoral trochlear angle and improve adaptability of the patellofemoral joint in children under the age of 8 years. But it had no obvious influence on older than 8-year-old children.
ABSTRACT
In this study we calculate theoretically and use FEM to simulate the effect of plate position relative to bending direction on the overall bending stiffness of the composite system plate-bone. The results show that for different bending directions the effect of the modulus of elasticity of the plate is negligible. Changing the position of a plate will often alter the stress obviously. During the operation, the steel plate should be assigned onto the tension side of the bone.