Sonic hedgehog signaling controls thalamic progenitor identity and nuclei specification in mice.

The mammalian thalamus is located in the diencephalon and is composed of dozens of morphologically and functionally distinct nuclei. The majority of these nuclei project axons to the neocortex in unique patterns and play critical roles in sensory, motor, and cognitive functions. It has been assumed that the adult thalamus is derived from neural progenitor cells located within the alar plate of the caudal diencephalon. Nevertheless, how a distinct array of postmitotic thalamic nuclei emerge from this single developmental unit has remained largely unknown. Our recent studies found that these thalamic nuclei are in fact derived from molecularly heterogeneous populations of progenitor cells distributed within at least two distinct progenitor domains in the caudal diencephalon. In this study, we investigated how such molecular heterogeneity is established and maintained during early development of the thalamus and how early signaling mechanisms influence the formation of postmitotic thalamic nuclei. By using mouse genetics and in utero electroporation, we provide evidence that Sonic hedgehog (Shh), which is normally expressed in ventral and rostral borders of the embryonic thalamus, plays a crucial role in patterning progenitor domains throughout the thalamus. We also show that increasing or decreasing Shh activity causes dramatic reorganization of postmitotic thalamic nuclei through altering the positional identity of progenitor cells.

Association of Comorbidity, Age, and Radical Surgical Therapy for Prostate Cancer, Bladder Cancer, and Renal Cell Carcinoma.

OBJECTIVE: To assess trends and factors driving aggressive surgery for patients >75 years diagnosed with prostate cancer (PCa), bladder cancer (BCa), and renal cell carcinoma (RCC). METHODS: We identified all patients >75 years diagnosed with PCa, BCa, and RCC from the Surveillance, Epidemiology and End Results-Medicare registry during 1992-2009. We analyzed the comorbidity and trends in radical cystectomy (RC), nephrectomy, and radical prostatectomy (RP) for these cohorts. Predictive factors for receiving aggressive surgery were assessed using logistic regression analysis. RESULTS: We identified cohorts of 85,073 PCa, 44,801 BCa, and 10,737 RCC patients. Among the BCa patients, 5.75% underwent RC and 78.2% had a Charlson comorbidity score (CCS) of ≤1. The trend of RC did not change significantly. There was a significant change in receipt of RP (P = .01). There were 85.8% of PCa patients who had a CCS ≤1 and 2.67% underwent RP. Approximately 65.2% of RCC patients had nephrectomy whereas 76.2% had CCS of ≤1. There was a decline in receipt of nephrectomies (P < .0001). Younger age, high stage or grade disease, and lower comorbidity were associated with higher odds of receiving RC, RP, and nephrectomy. CONCLUSION: In addition to stage and grade, age remains an important factor influencing the decision to undergo curative surgical therapy for PCa, BCa, and RCC patients >75 years. Comorbidity is also predictive, but to a lesser extent.

Trends in PET Scan Usage for Imaging of Patients Diagnosed With Nonmetastatic Urologic Cancer.

UNLABELLED: The precise utility of positron emission tomography (PET) scanning for urologic cancers is not well defined. We examined the trends of usage in a population-based data set. PET scans were performed in 3.60% of patients with bladder cancer, 1.09% of those with prostate cancer, and 5.32% of those with renal cell carcinoma. This selective usage might be driven by reimbursement constraints or identification of appropriate medical indications. INTRODUCTION: Positron emission tomography (PET) scanning is increasingly being used for imaging a variety of cancers, including urologic cancers. The precise utility of PET scanning for bladder cancer, prostate cancer, and renal cell carcinoma (RCC) is not yet well known. We examined the trends in PET scan usage for 3 cancers using a large population-based data set. MATERIALS AND METHODS: We analyzed all individuals identified with a diagnosis of nonmetastatic bladder cancer, prostate cancer, and RCC from the Surveillance, Epidemiology, and End Results-Medicare data set for 2004 to 2009 with follow-up data available to 2010. Logistic regression analysis and χ(2) and trend tests were performed to determine the predictors of performing PET scanning. Separate models were run for each of the cancer diagnoses. All analyses were performed using SAS, version 9.3, and P < .05 was considered significant. RESULTS: We identified 20,865, 70,414, and 7007 patients with a diagnosis of bladder cancer, prostate cancer, and RCC, respectively, from 2004 to 2009. PET scans had been performed for 3.60% of patients with bladder cancer, 1.09% of those with prostate cancer, and 5.32% of those with RCC. On regression analysis, a more recent year of diagnosis, younger age, and high stage or grade were predictors of PET scan usage for patients with bladder cancer and RCC. A higher Gleason score and higher D'Amico risk group predicted imaging with prostate cancer. CONCLUSION: The usage of PET scanning for bladder cancer, prostate cancer, and RCC is increasing but still very selective. The selective use might be driven by a combination of reimbursement constraints and careful identification of the appropriate medical indication.

Regional expression of MTG genes in the developing mouse central nervous system.

Myeloid translocation gene (MTG) proteins are transcriptional repressors that are highly conserved across species. We studied the expression of three members of this gene family, MTGR1, MTG8, and MTG16 in developing mouse central nervous system by in situ hybridization. All of these genes are detected as early as embryonic day 11.5. Because these genes are known to be induced by proneural genes during neurogenesis, we analyzed the expression of MTG genes in relation to two proneural genes, Neurog2 (also known as Ngn2 or Neurogenin 2) and Ascl1 (also known as Mash1). While MTGR1 are generally expressed in regions that also express Neurog2, MTG8 and MTG16 expression is associated more tightly with that of Ascl1-expressing neural progenitor cells. These results suggest the possibility that expression of MTG genes is differentially controlled by specific proneural genes during neurogenesis.