A combined array-based comparative genomic hybridization and functional library screening approach identifies mir-30d as an oncomir in cancer

Oncomirs are microRNAs (miRNA) that acts as oncogenes or tumor suppressor genes. Efficient identification of oncomirs remains a challenge. Here we report a novel, clinically guided genetic screening approach for the identification of oncomirs, identifying mir-30d through this strategy. mir-30d regulates tumor cell proliferation, apoptosis, senescence, and migration. The chromosomal locus harboring mir-30d was amplified in more than 30% of multiple types of human solid tumors (n = 1,283). Importantly, higher levels of mir-30d expression were associated significantly with poor clinical outcomes in ovarian cancer patients (n = 330, P = 0.0016). Mechanistic investigations suggested that mir-30d regulates a large number of cancer-associated genes, including the apoptotic caspase CASP3. The guided genetic screening approach validated by this study offers a powerful tool to identify oncomirs that may have utility as biomarkers or targets for drug development.     

Specific expression profile and prognostic significance of peroxiredoxins in grade II-IV astrocytic brain tumors

Background  

Peroxiredoxins (Prxs) have recently been suggested to have a role in tumorigenesis.     

The incidence of knee arthroplasty for primary osteoarthritis grows rapidly among baby boomers: A population‐based study in Finland

Objective

Total knee arthroplasty (TKA) is a commonly used treatment for severe primary knee osteoarthritis (OA) that is refractory to conservative treatment. Despite the presumed increase in the use of this treatment modality in younger patients, there are few published data concerning this. The aim of our study was to examine the changes in the age‐ and sex‐standardized incidence of TKA and unicondylar knee arthroplasty (UKA) in Finland during 1980–2006 and to identify factors that might affect the incidence during this period.

Methods

We obtained data on UKAs and TKAs from the Finnish Arthroplasty Registry and population data from Statistics Finland to analyze the incidence of UKAs and TKAs in Finland for the period 1980–2006. The effects of sex, age group, and hospital volume on the incidence of these procedures were also evaluated.

Results

The annual cumulative incidence of UKAs and TKAs has increased rapidly from 1980 to 2006 among 30–59‐year‐old inhabitants of Finland. For UKAs, the incidence increased from 0.2 per 100,000 inhabitants to 10 per 100,000, and for TKAs, the incidence increased from 0.5 per 100,000 to 65 per 100,000. The incidence remained higher among women during the entire study period. Most of the increase occurred among patients ages 50–59 years. The incidence grew more rapidly in low‐volume and intermediate‐volume hospitals.

Conclusion

We demonstrated a rapid increase in the incidence of arthroplasty among patients with primary knee OA in Finland, especially in those ages 50–59 years. There was no single explanatory factor behind this finding, although some of the growth might be due to the increased incidence noted in low‐ and intermediate‐volume hospitals.

     

Combination of serum hCG beta and p53 tissue expression defines distinct subgroups of serous ovarian carcinoma

Serous ovarian carcinoma comprises a clinically heterogenous group of tumors, and molecular markers stratifying patients into clinically meaningful subgroups are needed. Numerous markers have been evaluated, but none of them has yet been routinely incorporated into clinical practice. Previously we have found that elevated serum levels of the free beta subunit of human chorionic gonadotropin (hCG beta) and aberrant p53 expression confer poor prognosis in ovarian carcinoma. The aim of our study was to evaluate their combined effect in predicting the outcome of patients with serous ovarian carcinoma. The study material consisted of 173 consecutive patients treated for primary serous ovarian carcinoma in 1 institution between 1990 and 2000. The preoperative serum level of hCG beta was analyzed by a ultrasensitive and specific immunofluorometric assay, and p53 tumor tissue expression by immunohistochemistry using a novel classification. Elevated serum hCG beta (>or=2.0 pmol/L) was detected in 57 (33%) of 173 patients, and aberrant p53 expression in 103 (62%) of 167 interpretable cancers. Elevated hCG beta and aberrant p53 expression were strongly associated with poor prognosis (p < 0.0001 for both). Their additive prognostic effect was marked. Five-year survival was 14% (0-29%) when both markers were aberrant, 44% (29-60%) when either one was aberrant and 82% (70-94%) when both were normal. Preoperative serum hCG beta and tumor tissue p53 expression are feasible markers that divide serous ovarian carcinomas into clinically relevant subgroups.     

Polarized expression of Na+/H+ exchange activity in LLC-PK1/PKE20 cells: II. Hormonal regulation

LLC-PK₁/PKE₂₀ cells (a continuous epithelial cell line) has two different Na/H exchange activities: Na/H-1 located in the basolateral membrane and Na/H-2 located in the apical membrane [Casavola et al. (1989) Biochem Biophys Res Commun 165:833–837; Haggerty et al. (1988) Proc Natl Acad Sci USA 86:6797–6801]. In the present report we have studied hormone regulation of these exchange activities by measuring Na-dependent recovery of pH_i from an acid load (by using microspectrofluorometry and 2,7-bis(carboxyethyl)-5,6-carboxyfluorescein) in response to activation of regulatory cascades by either pharmacological agents or by vasopressin or calcitonin. Agents leading to activation of protein kinase A (cAMP-dependent), such as forskolin (10 M), 8-Br-cAMP (0.25 mM), and isobutylmethylxanthine (0.5 mM), inhibited Na/H-2 and Na/H-1 by an average of 49%. Stimulation of protein kinase C by a phorbol ester (phorbol 12-myristate 13-acetate, TPA, 100 nM) inhibited Na/H-2 (by an average of 48%) and stimulated Na/H-1 (by an average of 38%); these effects of TPA were also observed in the presence of forskolin (100 M). Addition of either vasopressin (2 M) or calcitonin (0.3 M) onto both sides of the monolayer decreased the activity of Na/H-2 by an average of 26.3% and 27.7% respectively, and stimulated the activity of Na/H-1 by an average of 17.4% and 38.7% respectively; exposure of cells to either hormone stimulated production of cAMP and inositol trisphosphate, respectively. Separate hormone additions to either the apical or basolateral cell surface led to effects similar to those produced by simultaneous hormone additions onto both cell surfaces, although the relative response of Na/H exchangers to either agonist is variable. In summary, these results suggest that in LLC-PK ₁/PKE₂₀ cells, vasopressin and calcitonin can act via receptor systems coupled either to adenylate cyclase or to phospholipase C. Activation of these receptor systems can lead to inhibition of Na/H-2 and stimulation of Na/H-1.     

What must the family practitioner know about spinal injuries

Spine injuries in a general practitioner's environment are mainly related to osteoporosis fractures in the elderly as well as cervical spine injuries in the elderly especially fractures of the odontoid process that need to be excluded if there is any suspicion. For osteoporotic spine fractures the invention of vertebroplasty offers a new treatment option and therefore patients should be transferred to a spine surgeon for further evaluation. The fracture of the odontoid process can end up in a non-union problem if not treated early; therefore this injury must be excluded in patients after sustaining any head contusion and complaints of neck pain afterwards.     

Perioperative myocardial infarction has negative impact on health-related quality of life following coronary artery bypass graft surgery.

OBJECTIVE: Perioperative myocardial infarction (PMI) is a well-described complication of coronary artery bypass grafting (CABG). Data on its effect on patients' subsequent health-related quality of life (QOL) and on other related consequences is deficient. The aim here was to evaluate in a prospective follow-up design the risk factors for and consequences of PMI and especially its possible impact on health-related QOL. METHODS: Comprehensive data, including preoperative risk profile, perioperative variables and postoperative morbidity up to discharge were collected of 501 CABG patients in the Heart Center of Tampere University Hospital and in all eighteen postoperative care hospitals. Eighty patients (16%) fulfilled ECG or cardiac enzyme criteria for PMI and they were compared to patients with no PMI. The RAND-36 Health Survey (RAND-36) was used as an indicator of QOL. The primary outcomes were change in physical component summary (PCS), mental component summary (MCS) and the eight dimensions of health-related QOL from the RAND-36. Symptomatic status was estimated according to New York Heart Association (NYHA) class. Assessments were made preoperatively and repeated 12 months later. RESULTS: Multivariate logistic regression analysis identified long cardiopulmonary bypass time (P=0.006) and high age (P=0.049) as independent predictors for PMI. Thirty-day mortality was adversely affected by PMI (6.3 vs 1.0%, P=0.001). In discharged patients, the occurrence of PMI did not affect 1-year survival adversely (98.7 vs 98.6%). The PMI patients showed significant (P<0.05) improvements in six of the eight dimensions of RAND-36, but they presented with a negative change in their 'general health' scores at the follow-up. All QOL scores improved significantly (P<0.001) among the patients without PMI. A highly significant (P<0.001) pattern of change was seen in the RAND-36 PCS and MCS scores in both groups although PMI patients showed significantly (P=0.002) smaller change in their PCS scores. Both groups showed similar freedom from anginal symptoms at 1 year (89.6 vs 90.1%) but in the PMI group later readmissions due to cardiac-related causes were more common (23 vs 10%, P=0.002). CONCLUSIONS: PMI increases 30-day mortality and affects also adversely on later health-related QOL following CABG.