Transplanted L1 expressing radial glia and astrocytes enhance recovery after spinal cord injury

A major obstacle for the transplantation of neural stem cells (NSCs) into the lesioned spinal cord is their predominant astrocytic differentiation after transplantation. We took advantage of this predominant astrocytic differentiation of NSCs and expressed the paradigmatic beneficial neural cell adhesion molecule L1 in radial glial cells and reactive and nonreactive astrocytes as novel cellular vehicles to express L1 under the control of the promoter for the human glial fibrillary acidic protein (GFAP-L1 NSCs). Behavioral analysis and electrophysiological H-reflex recordings revealed that mice transplanted with GFAP-L1 NSCs showed enhanced locomotor recovery in comparison to mice injected with wild type (WT) NSCs or control mice injected with phosphate-buffered saline (PBS). This functional recovery was further accelerated in mice transplanted with L1-expressing radial glial cells that had been immunoisolated from GFAP-L1 NSCs (GFAP-L1-i cells). Morphological analysis revealed that mice grafted with GFAP-L1 NSCs exhibited increased neuronal differentiation and migration of transplanted cells, as well as increased soma size and cholinergic synaptic coverage of host motoneurons and increased numbers of endogenous catecholaminergic nerve fibers caudal to the lesion site. These findings show that L1-expressing astrocytes and radial glial cells isolated from GFAP-L1 NSC cultures represent a novel strategy for improving functional recovery after spinal cord injury, encouraging the use of the human GFAP promoter to target beneficial transgene expression in transplanted stem cells.     

Impact of adjuvant androgen deprivation therapy after radical prostatectomy on the survival of patients with pathological T3b prostate cancer

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Adjuvant hormonal therapy is known to improve cancer specific survival in prostate cancer patients with lymph node positive disease. This study suggests that surgically treated prostate cancer patients with seminal vesical invasion (pT3b) may have improved cancer specific survival if treated with adjuvant androgen deprivation therapy, similar to lymph node positive patients.

OBJECTIVE

To determine the impact of adjuvant androgen deprivation therapy (ADT) on survival in patients with seminal vesicle invasion (pT3b) at radical prostatectomy.

PATIENTS AND METHODS

We reviewed 12 115 patients who underwent radical prostatectomy between 1987 and 2002 to identify patients with pT3bN0 prostate cancer who received adjuvant ADT (n= 191). These patients were matched by clinical and pathological variables to a group of patients with pT3b prostate cancer who did not receive adjuvant ADT. Median postoperative follow‐up was 10 years. Clinical endpoints included biochemical progression‐free survival (BPFS), local recurrence‐free survival (LRFS), systemic progression‐free survival (SPFS), cancer‐specific survival (CSS) and overall survival.

RESULTS

Patients who underwent adjuvant ADT experienced improved 10‐year BPFS (60% vs 16%, P < 0.001), LRFS (87% vs 76%, P= 0.002), SPFS (91% vs 78%, P= 0.004) and CSS (94% vs 87%, P= 0.037). Overall survival was not significantly different between groups (75% vs 69%, P= 0.12). Both luteinizing hormone‐releasing hormone agonists (hazard ratio, 0.26; 95% CI, 0.15–0.46; P < 0.001) and bilateral orchiectomy (hazard ratio, 0.13; 95% CI, 0.06–0.31; P < 0.001) improved BPFS. When stratified by type of ADT (hormonal therapy vs orchiectomy), there was no difference in survival outcomes.

CONCLUSIONS

Adjuvant ADT improves local, and systemic control after radical prostatectomy for pT3b prostate cancer. There is no difference in survival between patients receiving medical hormonal therapy vs patients undergoing orchiectomy. Given the lack of improvement in overall survival, continued investigation is needed to identify the cohort of pT3b patients at highest risk for cancer progression and therefore most likely to benefit from a multimodal treatment approach.