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PubMed2006

Increase in DNA fragmentation and apoptosis-related gene expression in frozen-thawed bovine blastocysts.

Evaluation of apoptosis and expression level of apoptosis-related genes is useful for examining the variation in embryo quality according to environmental change. The objective of this study was to investigate DNA fragmentation and apoptosis-related gene expression patterns in frozen-thawed bovine blastocysts. In vitro produced day 7 blastocysts were frozen by two different vitrification methods (conventional 0.25 ml straw or MVC straw). After thawing, DNA fragmentation of surviving embryos was examined by TUNEL assay, and the expression patterns of their apoptotic genes (survivin, Fas, Hsp 70 and caspase-3) were evaluated using real-time quantitative reverse transcriptase polymerase chain reaction. In vitro survival rates of frozen-thawed embryos were higher following the MVC vitrification method (88.2% re-expanded at 24 h, 77.1% hatching at 48 h) than the conventional (C) vitrification method (77.0% re-expanded at 24 h, 66.7% hatching at 48 h). However, both vitrified methods resulted in a significantly higher apoptotic index (C vitrification method 11.9%, MVC vitrification method 11.0%) than in non-frozen embryos (3.0%). Expression levels of survivin, Fas, caspase-3, and Hsp 70 were also increased in the frozen-thawed embryos compared with non-frozen embryos. These results indicate that the cryopreservation procedure might cause damage that results in an increase in DNA fragmentation and apoptosis-related gene transcription, reducing developmental capacity of frozen-thawed embryos.

Animals↗
PubMed2004

Ribonucleotide reductase messenger RNA expression and survival in gemcitabine/cisplatin-treated advanced non-small cell lung cancer patients.

PURPOSE: No chemotherapy regimen, including the widely used combination of gemcitabine/cisplatin, confers significantly improved survival over any other in metastatic non-small cell lung cancer (NSCLC); however, the selection of patients according to key genetic characteristics can help to tailor chemotherapy. Ribonucleotide reductase subunit M1 (RRM1) is involved in DNA synthesis and repair and in gemcitabine metabolism, and the excision repair cross-complementing group 1 (ERCC1) gene has been related to cisplatin activity. EXPERIMENTAL DESIGN: Patients were part of a large randomized trial carried out from September 1998 to July 2000, comparing gemcitabine/cisplatin versus gemcitabine/cisplatin/vinorelbine versus gemcitabine/vinorelbine followed by vinorelbine/ifosfamide. We analyzed RRM1 and ERCC1 mRNA expression in paraffin-embedded samples obtained from bronchoscopy by real-time quantitative reverse transcription-PCR. Results were correlated with survival using the Kaplan-Meier method. RESULTS: A total of 100 patients were assessed. There was a strong correlation between RRM1 and ERCC1 mRNA expression levels (Spearman r = 0.410; P < 0.001). In the gemcitabine/cisplatin arm, patients with low RRM1 mRNA expression levels had significantly longer median survival than those with high levels [13.7 versus 3.6 months; 95% confidence interval (CI), 9.6-17.8 months; P = 0.009]. Median survival was also significantly longer among patients with low mRNA expression levels of both RRM1 and ERCC1 (not reached), than among those with high levels of both genes (6.8 months; 95% CI, 2.6-11.1 months; P = 0.016). CONCLUSIONS: RRM1 mRNA expression is a crucial predictive marker of survival in gemcitabine/cisplatin-treated patients. Genetic testing of RRM1 mRNA expression levels can and should be used to personalize chemotherapy.

Adult↗
PubMed1992

Graphical representation of survival curves associated with a binary non-reversible time dependent covariate.

The use of time dependent covariates has allowed for incorporation into analysis of survival data intervening events that are binary and non-reversible (for example, heart transplant, initial response to chemotherapy). We can represent this type of intervening event as a three-state stochastic process with a starting state (S), an intervening state (I), and an absorbing state (D), which usually represents death. In this paper we present three procedures for calculating survivorship functions which attempt to display the prognostic significance of the time dependent covariate. The first method compares survival from baseline for the two possible paths through the stochastic process; the second method compares overall survival to survival with state I removed from the process; and, the third method compares survival for those already in state I at a landmark time x to those in state S at time x who will never enter state I. We develop discrete hazard estimates for the survival curves associated with the three methods. Two examples illustrate how these methods can yield different results and in which situations one might employ each of the three methods. Extensions to applications with reversible binary time dependent covariates and models with both baseline and time dependent covariates are suggested.

Data Interpretation, Statistical↗
PubMed2006

Expression of cytokeratin-20 in pancreatic cancer: an indicator of poor outcome after R0 resection.

BACKGROUND: After complete removal of the neoplasm (R0 resection), approximately 80% of pancreatic cancer patients will die of the disease within 5 years. The expression panel of cytokeratins (CK) is linked closely with cell differentiation. The aim of the study was to investigate the expression of CK-20 in pancreatic cancer tissue and to correlate CK-20 expression with survival in R0-resected pancreatic cancer patients. METHODS: Tissue samples of 63 patients with pancreatic cancer were subjected to CK-20 reverse-transcription polymerase chain reaction. Thirty-four of 63 patients underwent R0 resection and were followed-up for survival statistics. From these 34 patients, 26 (76%) neoplasms were CK-20 positive and 8 (24%) samples were CK-20 negative. The mean follow-up period for the entire group was 17 months (range, 4-36 mo), the follow-up period in censored patients was 23 months (range, 10-36 mo). RESULTS: In the R0-resected group, 3 of 8 (38%) patients with CK-20-negative neoplasms, and 16 of 26 (62%) patients with CK-20-positive neoplasms (P = .15) died of recurrent disease. The median survival time of patients with CK-20-positive neoplasms was 13 months (range, 4-36), the median survival in R0-resected patients with CK-20-negative neoplasm was 26 months (range, 13-35; P = .06). The survival difference observed in patients with CK-20-negative neoplasms could not be attributed to intergroup variations in tumor stage or tumor grade. CONCLUSIONS: A majority of primary ductal pancreatic adenocarcinomas express CK-20. This seems to be associated with poorer survival in R0-resected patients. Our data suggest that ductal pancreatic adenocarcinomas negative for CK-20 constitute a subgroup of patients showing a more favorable disease outcome. The expression of CK-20 in resected pancreatic cancer may be of interest as a prognostic parameter.

Carcinoma, Pancreatic Ductal↗
PubMed2002

Expression of smooth muscle calponin in tumor vessels of human hepatocellular carcinoma and its possible association with prognosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a vascular-rich tumor. The tumor vessels in HCC were demonstrated to have alpha-smooth muscle actin positive smooth muscle cells (SMCs). However, it is unclear whether the SMCs in the wall of the tumor vessels are differentiated or undifferentiated. Basic calponin is an actin-, tropomyosin-, and calmodulin-binding protein, and expression of the calponin gene in SMCs has been recognized as one of the late stage differentiation markers of SMCs. The authors investigated the differentiation state of SMCs in tumor vessels by immunohistochemical examination of calponin in patients with HCC, and whether it is associated with the patients' prognosis. METHODS: Tumor and nontumor tissues were obtained from 75 patients with HCC who underwent radical hepatic resection. The differentiation state of the smooth muscle cells were evaluated based on the expression level of calponin, an actin-binding protein, using immunohistochemistry and reverse transcription-polymerase chain reaction analysis. The disease free survival (DFS) rates were estimated according to the Kaplan-Meier method comparing groups of patients with calponin positive and negative tumor vessels. A multivariate analysis based on the Cox proportional hazards regression model was performed to estimate whether the expression of calponin is an independent prognostic factor. RESULTS: In the 75 patients with HCC examined, 36 patients (48%) possessed calponin positive SMCs, and the remaining 39 (52%) did not. There were no significant differences in either clinical or pathologic factors between the two groups of patients. The 5- and 8-year DFS rate of the patients with calponin positive vessels were 37% and 26%, respectively. These values were significantly higher (11% and 5%) than those of patients with calponin negative vessels. Gender, TNM classification, perioperative transfusion, and calponin expression were found to be independent prognostic factors for DFS. CONCLUSIONS: Immunohistochemical examination of the calponin expression in the tumor vessels is a new and useful means to predict the prognosis of HCC patients after hepatic resection.

Aged↗
PubMed1997

[Clinical significance of detection of PML-RAR alpha fusion gene of APL during differentiation therapy with ATRA].

OBJECTIVE: To characterize of the expression patterns of PML-RAR alpha fusion gene during differentiation therapy with ATRA. METHODS: A "neated" RT/PCR was established and subsequently used to study on 74 Acute Promyelocytic Leukemia (APL). RESULTS: Two major isoforms (type S and L) were detected in leukemia cells from 44 novel patients with APL. 19 of 44 (43.2%) patients with type S isoforms were accompanied with poor prognosis. 15 cases were detected sequentially by the RT/PCR method for dynamic observation of MSD during postremission therapy with ATRA and chemotherapy alternatly. The positive rate was 46.7% in 6 months after CR, then the positive rate curve tended to down wards gradually from 33.5% (12 months after CR) to 26.7% (24 months after CR), 11.1% (36 months after CR), 8.3% on 48 months after CR. Other 30 cases of APL which are long-term survivals and received the same postremission program were detected by the RT/PCR method. The expression of the fusion gene reversed positivty in two cases on 56 and 60 months respectively, then both relapsed. One case was detected regularly once a year for 3 times. In another case, the fusion gene was detectable whoever was no any abnormal evidence in peripheral blood and bone marrow 26 cases were negative and had a long-term survival CCR of 47-114 months (medium 66). CONCLUSION: The detection of RT/PCR PML-RAR alpha fusion gene plays an important role in clinical diagnosis, evaluation of prognosis and prediction of relapse in APL.

Adolescent↗
PubMed1991

Anesthetic and postoperative protocols for a canine model of reversible left ventricular volume overload.

The purpose of this study was to develop anesthetic and postoperative methods that could be used in a canine model of reversible left ventricular volume overload (LVVO). LVVO was created by inducing mitral regurgitation (MR) in adult conditioned dogs. Using fluoroscopy, MR was induced by passing urologic grasping forceps into the left ventricle through a carotid artery and rupturing one or more chordae tendinea. Cardiac catheterization was performed after significant cardiac dysfunction developed (3 months after creation of MR) in order to collect data to confirm reduced contractile function. The MR was repaired by replacing the damaged valve with a bovine pericardial xenograft. Dogs were followed with sequential cardiac catheterizations to determine if the valvular replacement reversed the cardiac dysfunction. To develop this model, unique anesthetic and post-operative care protocols had to be instituted. In order not to exacerbate the existing cardiac dysfunction, a high dose narcotic anesthetic regimen using a sufentanil infusion at 9-13 microgram/kg h-1 was developed in association with cardiopulmonary bypass and hypothermia for the mitral valve replacement surgery. Intensive postoperative care protocols that involved major personnel and pharmaceutic interventions were necessary. Using our methods 11/17 dogs survived the procedure and were included in the protocol for study of mechanisms involved in reversal of cardiac dysfunction.

Anesthesia↗
PubMed1998

Reduction in pulmonary vascular resistance with long-term epoprostenol (prostacyclin) therapy in primary pulmonary hypertension.

BACKGROUND: Primary (idiopathic) pulmonary hypertension is a progressive, fatal disease. Conventional therapy with anticoagulant and vasodilator drugs may improve symptoms and survival among selected patients, but there is no evidence that the disease can be reversed. METHODS: We evaluated the effects of long-term therapy (i.e., for more than one year) with intravenous epoprostenol (prostacyclin) in patients with advanced primary pulmonary hypertension. The base-line evaluation included an assessment of pulmonary vascular dilation in response to intravenous adenosine. The epoprostenol dose was increased monthly to the maximum tolerated. Long-term therapy was evaluated by measuring improvement in symptoms, exercise capacity, and hemodynamic measures. RESULTS: We evaluated 27 patients with primary pulmonary hypertension over a mean (+/-SD) period of 16.7+/-5.2 months. Intravenous adenosine had a variable effect on pulmonary vascular resistance (mean reduction, 27 percent; range, 0 to 56; P<0.001). Epoprostenol therapy was initiated and the rate of infusion was increased by an average of 2.4 ng per kilogram of body weight per minute each month. Twenty-six of the 27 patients had improvement in symptoms and hemodynamic measures, and overall, pulmonary vascular resistance declined by 53 percent to 7.9+/-3.8 resistance units (P<0.001) at the time of restudy. The long-term effects of epoprostenol exceeded the short-term pulmonary vasodilator response to adenosine in all but one patient. Seven of the eight patients who had minimal pulmonary vasodilation in response to adenosine (mean reduction in resistance units, <20 percent) still had a significant reduction in pulmonary vascular resistance when treated with epoprostenol (mean, 39+/-14 percent; P=0.002). CONCLUSIONS: In primary pulmonary hypertension, long-term therapy with epoprostenol lowers pulmonary vascular resistance beyond the level achieved in the short term with intravenous adenosine. Epoprostenol appears to have sustained efficacy in this disorder.

Adult↗
PubMed2005

Catalytic subunit of human telomerase reverse transcriptase is an independent predictor of survival in patients undergoing curative resection of hepatic colorectal metastases: a multicenter analysis.

PURPOSE: To determine the role of the catalytic subunit of human telomerase reverse transcriptase (hTERT) in predicting survival after resection of hepatic colorectal metastases (CRM). PATIENTS AND METHODS: Two hundred one patients who underwent curative resection of hepatic CRM between 1990 and 2000 were identified from a multicenter database. The CRM were analyzed for hTERT nucleolar expression by standard immunohistochemical techniques. hTERT expression and known clinicopathologic factors of survival were examined. RESULTS: With a median follow-up of 80 months, 152 patients (75.6%) had died; the 5-year overall survival was 30.7%. On univariate analysis, number of metastases greater than two (P = .0005), extrahepatic disease (P = .0054), disease-free interval less than 12 months (P = .006), carcinoembryonic antigen level greater than 200 ng/mL (P = .0071), and positive hTERT nucleolar staining (P < .0001) were associated with decreased survival. On multivariate analysis, three factors independently predicted survival: number of metastases (relative risk [RR] = 1.74; P = .0011); disease-free interval (RR = 1.70; P = .0035); and positive hTERT nucleolar staining (RR = 2.03; P < .0001). Patients with none or one of these factors had a 5-year survival rate of 48%, whereas those with two or three of these factors had a 5-year survival of 15% (P < .0001). CONCLUSION: hTERT nucleolar expression is associated with worse survival after resection of hepatic CRM. hTERT expression in conjunction with number of hepatic metastases and disease-free interval may permit more accurate prediction of survival after resection of hepatic CRM.

Adult↗
PubMed2006

Increased detection rate and potential prognostic impact of disseminated tumor cells in patients undergoing endorectal ultrasound for rectal cancer.

BACKGROUND: Hematogenous tumor-cell dissemination during diagnostic and therapeutic procedures in patients with colorectal cancer has been demonstrated. OBJECTIVE: The aim of this study was to investigate the extent of disseminated tumor cells in blood samples of rectal cancer patients after endorectal ultrasound and to determine its prognostic relevance. MATERIALS AND METHODS: Peripheral venous blood samples from 45 patients with rectal cancer were taken before and after endorectal ultrasound. Blood samples were examined using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay to amplify cytokeratin 20 transcripts. Overall survival of the patients was calculated by the Kaplan-Meier method. RESULTS: Disseminated tumor cells were detected in peripheral blood samples of 17 of 45 (38%) patients before and after endorectal ultrasound. Circulating tumor cells were found in 11 of 45 (24%) patients only after endorectal ultrasound (p=0.006). There was a clear trend toward a worse prognosis in patients with tumor cells in blood samples after endorectal ultrasound, but this difference was not statistically significant. CONCLUSION: This study demonstrates significantly increased hematogenous tumor-cell dissemination after endorectal ultrasound in rectal cancer patients. Patients with tumor cells in blood samples after endorectal ultrasound tend to have a worse prognosis. The potential prognostic impact of this finding is presently unclear and has to be further validated in larger clinical trials.

Endoscopy, Gastrointestinal↗
PubMedDate not supplied

Resistance of cultured human skin fibroblasts from old and young donors to oxidative stress and their glutathione peroxidase activity.

BACKGROUND: It has been suggested that oxidative stress is involved in the aging process and that the resistance of animals to oxidative stress may decrease with advancing aging. However, there are only a limited number of reports of studies on the relationship between aging and resistance to oxidative stress. OBJECTIVE: The aim of this work is to examine the relationship between the resistance of human skin fibroblasts to oxidative stress and donor age, and the relevance of antioxidant enzyme activities to this resistance. METHODS: Percent cell survival was determined by the trypan blue exclusion test and the neutral red method. Superoxide dismutase activity was assayed by the method of Oyanagi, catalase activity by the method of Aebi, and glutathione peroxidase activity by the method of Flohé and Günzler. Reduced glutathione concentration was measured by the method of Griffith. Antioxidant enzyme mRNA levels were estimated by reverse transcription polymerase chain reactions (RT-PCR). RESULTS: The percent survivals of cultured human skin fibroblasts, derived from young and old donors (referred to as young and old cells, respectively), under oxidative stress from hydrogen peroxide, linoleic acid hydroperoxide, or ultraviolet light B were examined. Old cells were more resistant to such oxidative stress than young cells. The activity of glutathione peroxidase was higher by 46.1% in old cells than in young cells, although there was no difference between their relative glutathione peroxidase mRNA levels. Further, there was no difference between their activities of copper/zinc superoxide dismutase, manganese superoxide dismutase, or catalase. However, the relative mRNA levels of copper/zinc superoxide dismutase and manganese superoxide dismutase were lower by 13.9 and 20.9% in old cells than in young cells, respectively, while there was no difference between the levels of catalase. CONCLUSIONS: These results suggest that old cells are more resistant to oxidative stress than young cells, presumably because of an increase in cellular glutathione peroxidase activity.

Adult↗
PubMed1982

Mutability of bacteriophage M13 by ultraviolet light: role of pyrimidine dimers.

The role of pyrimidine dimers in mutagenesis by ultraviolet light was examined by measuring the UV-induced reversion of six different bacteriophage M13 amber mutants for which the neighboring DNA sequences are known. The mutational response at amber (TAG) codons preceded by a guanine or adenine (where no pyrimidine dimer can be formed) were compared with those preceded by thymine or cytosine (where dimer formation is possible). Equivalent levels of UV-induced mutagenesis were observed at both kinds of sites. This observation demonstrates that there is no requirement for a pyrimidine dimer directly at the site of UV-induced mutation in this single-stranded DNA phage. UV irradiation of the phage was also performed in the presence of Ag+ ions, which specifically sensitize the DNA to dimer formation. The two methods of irradiation, when compared at equal survival levels (and presumably equal dimer frequencies), produced equivalent frequencies of reversion of the amber phage. We believe these results indicate that while the presence of pyrimidine dimers may be a prerequisite for UV mutagenesis, the actual mutagenic event can occur at a site some distance removed from a dimer.

Base Sequence↗
PubMed2004

[A clinical study on the extended reverse digital artery island flap].

OBJECTIVE: To investigate the feasibility and clinical effect of the extended reverse digital artery island flap including dorsal digital nerve. METHODS: Since 2001, 7 cases of pulp and digital palm defects were repaired by the extended reverse digital artery island flap including dorsal digital nerve. RESULTS: All the flaps survived. Follow-up showed satisfactory results functionally and cosmetically with 2-PD of 6-9 mm. CONCLUSIONS: The extended reverse digital artery island flap is a safe and feasible and an effective method for repair of finger pulp defects.

Adolescent↗
PubMed1998

Relation between microsatellite instability and N-ras mutation and duration of disease free survival in patients with acute leukemia.

BACKGROUND: Microsatellite instability (MIN) appears to be a novel molecular mechanism in carcinogenesis and is believed to reflect multiple replication errors. The authors analyzed MIN in de novo acute leukemia and its association with expression of the human MSH3 (hMSH3) gene and point mutations of the N-ras gene. The relation between MIN and disease free survival also was examined. METHODS: The authors studied 43 cases of de novo acute leukemia for MIN at 5 loci. They also examined expression of the hMSH3 gene using the reverse transcriptase-polymerase chain reaction method. DNA taken from 36 cases at diagnosis was examined for N-ras mutations. The Kaplan-Meier method was used to estimate patients' disease free survival. RESULTS: MIN at 1 locus was found in 7 of the 43 cases (16%) (MIN positive [MIN+] group). There was no correlation between MIN+ and decreased hMSH3 gene expression. Four of the 7 MIN+ cases (57%) had a mutation of the N-ras gene compared with only 1 of the 29 MIN- cases (3%). A correlation between N-ras mutations and MIN was detected (P < 0.003). The MIN+ patients had a shorter disease free survival than the MIN- patients (P < 0.03). CONCLUSIONS: MIN may be associated with N-ras mutation in some cases of de novo acute leukemia and influence the duration of disease free survival.

Acute Disease↗
PubMed1998

A randomized, controlled, double-blind study comparing the survival benefit of four different reverse transcriptase inhibitor therapies (three-drug, two-drug, and alternating drug) for the treatment of advanced AIDS. AIDS Clinical Trial Group 193A Study Team.

OBJECTIVE: The primary objective was to compare the effects of dual or triple combinations of HIV-1 reverse transcriptase inhibitors with respect to survival. The time to new HIV disease progression or death, toxicities, the change in CD4 cells, and plasma HIV-1 RNA concentrations in a subset of study subjects were evaluated. DESIGN: This was a multicenter randomized, double-blind, placebo-controlled study. SETTING: The study was conducted among 42 adult AIDS Clinical Trials Group sites and 7 National Hemophilia Foundation centers. PATIENTS: 1313 HIV-infected patients with CD4 counts < or = 50 cells/mm3 participated in this study, which was conducted from June 1993 to June 1996. INTERVENTION: Patients were randomized to one of four daily regimens containing 600 mg of zidovudine: zidovudine alternating monthly with 400 mg didanosine; zidovudine plus 2.25 mg of zalcitabine; zidovudine plus 400 mg of didanosine; or zidovudine plus 400 mg of didanosine plus 400 mg of nevirapine (triple therapy). MAIN OUTCOME MEASURES: The main outcome was survival (i.e., time to death). RESULTS: A significant difference in survival time was found between the four treatment groups, favoring those assigned to triple therapy (p = .02). A significant difference was also found in the delay of disease progression or death among the four treatment arms favoring the group assigned to triple therapy (p = .002). Baseline CD4 cell counts and plasma HIV-1 RNA concentrations as well as changes of CD4 counts at week 8 predicted survival for subjects in the virology substudy. CONCLUSIONS: In the pre-protease inhibitor era, a combination of triple reverse transcriptase inhibitors prolonged life and delayed disease progression in AIDS patients with advanced immune suppression.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Effect of highly active antiretroviral therapy on survival in patients with AIDS-associated pulmonary Kaposi's sarcoma treated with chemotherapy.

PURPOSE: Kaposi's sarcoma (KS) is the most common AIDS-related malignancy. Pulmonary involvement by KS (PKS) has carried a poor prognosis with median reported survival ranging from 3 to 10 months. We studied whether the introduction of highly active antiretroviral therapy (HAART; triple antiretroviral therapy including a protease inhibitor and two reverse transcriptase inhibitors) has been associated with improved survival for AIDS patients with PKS. PATIENTS AND METHODS: A retrospective study was performed of 37 consecutive patients with PKS and human immunodeficiency virus infection in the tumor registry at a large municipal hospital in New York City between 1994 to 1997. There were 16 patients from 1994 to 1995 (pre-HAART period) and 21 patients from 1996 to 1997 (post-HAART period). The primary end point was survival, which was defined as time from start of chemotherapy until death from any cause. RESULTS: Patients were analyzed by the date of diagnosis (pre- v post-HAART period) and whether or not they received HAART. Kaplan-Meier analysis showed significantly better survival in patients diagnosed in the post-HAART period (P =.0025). Additional Kaplan-Meier analysis indicated that patients on HAART had substantially better survival (P <.0001). Cox multivariate analyses showed that HAART therapy was associated with a reduced risk of death (hazard ratio = 0.09; 95% confidence interval, 0.03 to 0.69). CONCLUSION: In patients with AIDS-associated PKS and undergoing chemotherapy, administration of HAART was associated with increased survival.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Levosimendan reversing low output syndrome after heart transplantation.

After heart transplantation primary graft failure is a major cause of early mortality. Treatment options include inotropes and mechanical assist devices. Developing better methods would impact on patients' short- and long-term survival. We present a case of primary graft failure manifested as cardiogenic shock unresponsive to catecholamines and a phosphodiesterase inhibitor. Reversal of low output syndrome was achieved with a new type of inotropic agent, levosimendan, leading to the later complete recovery.

Cardiotonic Agents↗
PubMed2004

Prognostic model of pulmonary adenocarcinoma by expression profiling of eight genes as determined by quantitative real-time reverse transcriptase polymerase chain reaction.

PURPOSE: Recently, several expression-profiling experiments have shown that adenocarcinoma can be classified into subgroups that also reflect patient survival. In this study, we examined the expression patterns of 44 genes selected by these studies to test whether their expression patterns were relevant to prognosis in our cohort as well, and to create a prognostic model applicable to clinical practice. PATIENTS AND METHODS: Expression levels were determined in 85 adenocarcinoma patients by quantitative reverse transcriptase polymerase chain reaction. Cluster analysis was performed, and a prognostic model was created by the proportional hazards model using a stepwise method. RESULTS: Hierarchical clustering divided the cases into three major groups, and group B, comprising 21 cases, had significantly poor survival (P =.0297). Next, we tried to identify a smaller number of genes of particular predictive value, and eight genes (PTK7, CIT, SCNN1A, PGES, ERO1L, ZWINT, and two ESTs) were selected. We then calculated a risk index that was defined as a linear combination of gene expression values weighted by their estimated regression coefficients. The risk index was a significant independent prognostic factor (P =.0021) by multivariate analysis. Furthermore, the robustness of this model was confirmed using an independent set of 21 patients (P =.0085). CONCLUSION: By analyzing a reasonably small number of genes, patients with adenocarcinoma could be stratified according to their prognosis. The prognostic model could be applicable to future decisions concerning treatment.

Adenocarcinoma↗