The trend toward high-throughput techniques in molecular biology and the explosion of online scientific data threaten to overwhelm the ability of researchers to take full advantage of available ...information. This problem is particularly severe in the rapidly expanding area of gene expression experiments, for example, those carried out with cDNA microarrays or oligonucleotide chips. We present an Internet-based hypertext program, MedMiner, which filters and organizes large amounts of textual and structured information returned from public search engines like GeneCards and PubMed. We demonstrate the value of the approach for the analysis of gene expression data, but MedMiner can also be extended to other areas involving molecular genetic or pharmacological information. More generally still, MedMiner can be used to organize the information returned from any arbitrary PubMed search.
Molecular crosstalk, including reciprocal stimulation, is theorized to take place between epithelial cancer cells and surrounding non-neoplastic stromal cells. This is the rationale for stromal ...therapy, which could eliminate support of a cancer by its genetically stable stroma. Epithelial-stromal crosstalk is so far poorly documented in vivo, and cell cultures and animal experiments may not provide accurate models. The current study details stromal-epithelial signalling pathways in 35 human colon cancers, and compares them with matched normal tissues using quantitative proteomic microarrays. Lysates prepared from separately microdissected epithelium and stroma were analysed using antibodies against 61 cell signalling proteins, most of which recognize activated phospho-isoforms. Analyses using unsupervised and supervised statistical methods suggest that cell signalling pathway profiles in stroma and epithelium appear more similar to each other in tumours than in normal colon. This supports the concept that coordinated crosstalk occurs between epithelium and stroma in cancer and suggests epithelial-mesenchymal transition. Furthermore, the data herein suggest that it is driven by cell proliferation pathways and that, specifically, several key molecules within the mitogen-activated protein kinase pathway may play an important role. Given recent findings of epithelial-mesenchymal transition in therapy-resistant tumour epithelium, these findings could have therapeutic implications for colon cancer.
The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting ...rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile.
A cost-effectiveness study was performed from the societal perspective.
To evaluate the costs and benefits of laminectomy alone and laminectomy with concomitant lumbar fusion for patients with ...degenerative lumbar spondylolisthesis and spinal stenosis.
Costs, probabilities, and utilities were estimated from the literature. Short-term risks considered were perioperative complications, the probability of the fusion healing, and the probability that surgery will relieve symptoms. Long-term risks considered were recurrence of symptoms and reoperation.
The 10-year costs, quality-adjusted life years, and incremental cost-effectiveness ratios (reported as dollars per quality-adjusted year of life gained) were calculated using a Markov model. Sensitivity analysis was performed on all variables using clinically plausible ranges.
Laminectomy with noninstrumented fusion costs $56,500 per quality-adjusted year of life versuslaminectomy without fusion. The cost-effectiveness of laminectomy with noninstrumented fusion was most sensitive to the increase in quality-of-life associated with relief of severe stenosis symptoms. The cost-effectiveness ratio of instrumented fusion compared with noninstrumented fusion was $3,112,800 per quality-adjusted year of life. However, if the proportion of patients experiencing symptom relief after instrumented fusion was 90% as compared with 80% for patients with noninstrumented fusion, then the cost-effectiveness ratio of instrumented fusion compared with noninstrumented fusion would be $82,400 per quality-adjusted year of life.
The cost-effectiveness of laminectomy with noninstrumented fusion compares favorably with other surgical interventions, although it depends greatly on the true effectiveness of these surgeries to alleviatesymptoms and on how patients value the quality-of-life effect of relieving severe stenosis symptoms. Instrumented fusion was very expensive compared with the incremental gain in health outcome. Better data on the effectiveness of these alternative procedures are needed.
The possible role of phospholipase A2 in an animal model for lumbar radiculopathy and mechanisms of epidural steroid injections were studied.
To clarify the pathophysiologic mechanism of the recently ...proved animal model for lumbar radiculopathy and to characterize further the mechanisms of action of steroids.
There have been several reported animal models of peripheral neuropathy. Recently an animal model that shows reliable behavioral and neurochemical changes was proposed, and epidural steroid injections in this model were effective in the reduction of thermal hyperalgesia and allodynia.
In a behavioral study, 24 rats were divided into 4 groups: Group I, loose ligature of the left L4 and L5 nerve roots with 4-0 chromic gut sutures and an epidural injection of 0.1 mL of saline at 3 days after surgery; Group II, same as Group I but with an epidural injection of 0.1 mL of betamethasone on the day before the operation; Group II, same as Group II except injection at 1 day after surgery; Group IV, same as Group II except injection at 3 days after surgery. To test the phospholipase A2 activity in the nerve roots and dorsal root ganglia after the operation, eight rats were killed at given intervals. Analysis of variance techniques were used to test behavioral pattern changes and phospholipase A2 activity across time in each group.
Thermal hyperalgesia reached its maximal point at 3 weeks after surgery in Group I, but in steroid injection groups, the recovery from hyperalgesia was faster than in Group I. However, there was no significant difference in recovery time among steroid injection groups. The level of phospholipase A2 activity was at its maximum at 1 week after surgery in Groups I and IV. It showed a steady reduction in the steroid group, whereas it remained relatively high and dropped rapidly after 3 weeks in the saline-treated group, and returned to the level of a normal nerve root at 6 weeks after surgery.
These results suggest that the behavioral pattern changes observed in the irritated nerve root model are caused in part by a high level of phospholipase A2 activity initiated by inflammation, and that the mechanism of action of epidural steroid injection in this model is inhibition of phospholipase A2 activity.
Prospective multicenter observational study of the outcome of surgery for degenerative lumbar spinal stenosis.
To identify correlates of patient satisfaction with the results of surgery.
Little ...published information exists on correlates of patient satisfaction after surgery for spinal stenosis.
Preoperative and 6-month follow-up data for 194 patients were analyzed. Associations between preoperative variables and satisfaction with the results of surgery were examined in univariate and multivariate models.
In multiple linear regression models that adjusted for the effects of age, gender, individual surgeon, number of interspaces decompressed, whether a fusion was performed, depression score, and overall level of pain, the predominance of back (as opposed to leg) pain, greater comorbidity, and worse preoperative functional status were associated with lower patient satisfaction. The regression model explained just 15% of the variance in patient satisfaction.
Patients bothered predominantly by back pain preoperatively and those with greater medical comorbidity and functional disability are significantly less satisfied with the results of surgery for degenerative lumbar spinal stenosis.
A consecutive series of 52 chordomas of the mobile spine observed over a 50-year period includes a retrospective review of 15 cases treated prior to 1991 and a prospective group of 37 cases treated ...from 1991 to 2002.
This series reviews epidemiologic issues as well as clinical patterns of spinal chordomas. We attempt to correlate tumor extent, treatment, and outcomes over time.
Chordoma is the most frequent primary tumor of the mobile spine. Due to slow growth, both initial symptoms and recurrences after treatment arise later, making it difficult to evaluate the effectiveness of treatment protocols.
A prospective series of 37 cases is compared with a retrospective group of 15 patients observed between 1954 and 1991. In the prospective study, all patients had imaging studies, and oncologic and surgical staging. When en bloc resection was not feasible, intralesional extracapsular excision was combined with radiation therapy. The prospective patients were clinically evaluated and imaged. Patients in the retrospective group were evaluated by chart and available images; of these, only one en bloc resection (intralesional margin) was performed. Survivors were all evaluated clinically and had radiographic studies.
Forty-eight patients were available for long-term follow-up. Four died due to post-operative complications, and six due to disease less than 2 years after treatment. Forty-two patients were followed over 2 years; 26 patients had over 5 years follow-up. All patients having radiation alone, intralesional excision, or a combination had recurrences in less than 2 years, and died in some cases after a long survival with symptomatic disease. Intralesional extracapsular excision with radiation had a high rate of recurrence (12 of 16 at average 30 months), but 3 patients are continuously disease-free (CDF) at mean 52 months and 5 are alive with disease at average 69 months (ranging 24 to 146). Twelve of 18 patients having en bloc resection are CDF at average 8 years (48 to 155 months). The remaining 6 recurred and of these 1 died. All of these (6) had been previously treated and/or had en bloc resections with contaminated margins.
The only treatment protocol associated with CDF at follow-up longer than 5 years is margin-free en bloc resection.
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