Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prostate-specific antigen (PSA) promoter (PSA-P) has been identified, characterized, and determined to be tissue specific. Compared with high expression of the genomic PSA gene in prostate cells, expression of the transgene driven by the putative PSA promoter is low. This suggests that the identified promoter may be incomplete or may function optimally with additional regulatory elements. To identify the presence of additional regulatory elements, we screened sequences upstream of the PSA promoter and identified a DNA fragment of 822 bp, which enhances PSA gene expression. Combining the newly identified PSA gene regulatory sequence (PSAR) with our previously identified PSA promoter (PCPSA-P) exhibited enhanced expressional activity in the PSA-producing LNCaP cell line. With the addition of 10 to 100 nM dihydrotestosterone, a more than 1000-fold increase in expression was observed as compared to androgen-negative controls. Furthermore, although the combined regulatory element (PSAR)-PSA promoter (PCPSA-P) sequence resulted in high transgene expression in LNCaP cell lines, the combined regulatory element-promoter sequence resulted in minimal expression in the non-PSA-producing prostate cell line PC-3, renal tumor cell line R11, and cervical adenocarcinoma cell line HeLa. The newly identified 822 bp alone could also function as a promoter. Compared with the combined promoter, however, the 822-bp fragment alone demonstrated lower activity and lower responsiveness to androgen stimulation. Our results suggest that coupling the PSA promoter with an upstream regulatory element results in a marked increase in PSA expression, suggesting that the complete PSA promoter contains two functional domains: a proximal promoter and a distal promoter, which can also function as an enhancer. The enhanced gene expression of the new construct, combined with its tissue specificity and androgen responsiveness, in turn provides a foundation for the development of tissue-specific vectors for prostate cancer gene therapy.
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PMID:Identification of a positive regulatory element responsible for tissue-specific expression of prostate-specific antigen. 901 80

OBJECT Nerve biopsy is typically performed in distal, noncritical sensory nerves without using imaging to target the more involved regions. The yield of these procedures rarely achieves more than 50%. In selected cases where preoperative evaluation points toward a more localized (usually a more proximal) process, targeted biopsy would likely capture the disease. Synthesis of data obtained from clinical examination, electrophysiological testing, and MRI allows biopsy of a portion of the major mixed nerves safely and efficiently. Herein, experiences with the sciatic nerve are reported and a description of the operative technique is provided. METHODS All cases of sciatic nerve biopsy performed between 2000 and 2014 were reviewed. Only cases of fascicular nerve biopsy approached from the buttock or the posterior aspect of the thigh were included. Demographic data, clinical presentation, and the presence of percussion tenderness for each patient were recorded. Reviewed studies included electrodiagnostic tests and imaging. Previous nerve and muscle biopsies were noted. All details of the procedure, final pathology, and its treatment implications were recorded. The complication rate was carefully assessed for temporary as well as permanent complications. RESULTS One hundred twelve cases (63 men and 49 women) of sciatic nerve biopsy were performed. Mean patient age was 46.4 years. Seventy-seven (68.8%) patients presented with single lower-extremity symptoms, 16 (14.3%) with bilateral lower-extremity symptoms, and 19 (17%) with generalized symptoms. No patient had normal findings on physical examination. All patients underwent electrodiagnostic studies, the findings of which were abnormal in 110 (98.2%) patients. MRI was available for all patients and was read as pathological in 111 (99.1%). The overall diagnostic yield of biopsy was 84.8% (n = 95). The pathological diagnoses included inflammatory demyelination, perineurioma, nonspecific inflammatory changes, neurolymphomatosis, amyloidosis, prostate cancer, injury neuroma, neuromuscular choristoma, sarcoidosis, vasculitis, hemangiomatosis, arteriovenous malformation, fibrolipomatous hamartoma (lipomatosis of nerve), and cervical adenocarcinoma. The series included 11 (9.9%) temporary and 5 (4.5%) permanent complications: 3 patients (2.7%) reported permanent numbness in the peroneal division distribution, and 2 patients (1.8%) were diagnosed with neuromuscular choristoma that developed desmoid tumor at the biopsy site 3 and 8 years later. CONCLUSIONS Targeted fascicular biopsy of the sciatic nerve is a safe and efficient diagnostic procedure, and in highly selected cases can be offered as the initial procedure over distal cutaneous nerve biopsy. Diagnoses were very diverse and included entities considered very rare. Even for the more prevalent diagnoses, the biopsy technique allowed a more targeted approach with a higher diagnostic yield and justification for more aggressive treatment. In this series, new radiological patterns of some entities were identified, which could be biopsied less frequently.
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PMID:Targeted fascicular biopsy of the sciatic nerve and its major branches: rationale and operative technique. 2632 14