Mental state as a possible independent prognostic variable for survival in patients with advanced lung carcinoma

BACKGROUND: Although psychologic factors have been reported to influence the progression of cancer, this theory remains controversial. A prospective study of patients with advanced lung carcinoma was performed to explore the influence of the patient's mental state on survival. METHODS: The patient's mental state was assessed with the Tokyo University Egogram. In a preliminary study, the egograms of long-term survivors (survival > 3 years) with TNM Stage IIIB or Stage IV lung carcinoma were compared with the egograms of consecutive, newly diagnosed lung carcinoma patients (controls). Next, in a prospective study, 123 patients with nonsmall cell lung carcinoma and 56 patients with small cell lung carcinoma (Stage IIIB or Stage IV; Eastern Cooperative Oncology Group performance status of 0 or 1) completed the egogram. Based on the results of the preliminary study, the subjects in the prospective study were divided into Group A (Free Child [FC] >or= 50th percentile and Adapted Child [AC] < 50th percentile) and Group B (FC < 50 percentile or AC >or= 50 percentile). The survival of the two groups was compared. The Cox proportional hazards model was used to determine the joint effect of the patient's mental state and other prognostic factors. RESULTS: In the preliminary study, the FC score of the long-term survivors was significantly higher and the AC score was significantly lower than those of the controls. In the prospective study, the survival of Group A was significantly longer than that of Group B both in the nonsmall cell lung carcinoma and small cell lung carcinoma patients (P = 0.002 and P = 0.005, respectively, by the log-rank test). Multivariate analysis demonstrated that after adjustment for clinical factors, being in Group A was a significant predictor of survival both in the nonsmall cell and small cell lung carcinoma patients. CONCLUSIONS: The results of the current study demonstrate that the mental state of the patient as assessed by the egogram may have prognostic significance in patients with advanced lung carcinoma.     

Effects of exposure of CHO-K1 cells to a 10-T static magnetic field

PURPOSE: To evaluate whether exposure to strong static magnetic fields (SMFs), of up to 10 T, affects the growth and cycle distribution of and the micronucleus formation in monolayered Chinese hamster ovary CHO-K1 cells. MATERIALS AND METHODS: The authors developed a system to expose cultured cells to strong SMFs immediately after the cells are seeded. Cell growth rate was evaluated according to cell number count. Cell cycle distribution experiments were performed by using flow cytometric analysis. In these experiments, the cells were exposed to SMFs for up to 4 days. The frequency of micronucleus formation with only SMF exposure at x-ray irradiation was analyzed at microscopic observation. RESULTS: Long-term exposure to a 10-T SMF for up to 4 days did not affect cell growth rate or cell cycle distribution. Exposure to SMFs alone did not affect micronucleus frequency. In x-ray-irradiated cells, exposure to a 1-T SMF did not affect micronucleus frequency, but exposure to a 10-T SMF resulted in a significant (P <.05) increase in micronucleus frequency. CONCLUSION: Strong (10-T) SMFs have no effect on cell growth, cell cycle distribution, or micronucleus frequency, but they may cause an increase in the micronucleus formation induced by 4-Gy x rays.     

Quantitative assessment of right ventricular structural abnormalities by right ventricular polar mapping of single photon emission computed tomogram

The identification of right ventricular (RV) abnormalities is clinically important in the evaluation of arrhythmogenic substrates in right ventricular-originated ventricular tachycardia (RVT). The purpose of this study was to determine the diagnostic benefit of quantitative analysis in RV single photon emission computed tomography (SPECT) imaging with (99m)Tc-tetrofosmin/sestamibi in patients with RVT. Thirty patients with RVT (15 with idiopathic RVT and 15 with arrhythmogenic right ventricular cardiomyopathy (ARVC)) were compared with 27 control subjects (including 11 with right bundle branch block) with regard to the semiquantitative RV uptake score in each of six segments and the quantitative RV extent score in polar coordinate map displays by SPECT imaging. The RV total score and RV extent score were compared with the RV global function. Perfusion abnormalities were more frequently detected (P = 0.0001) in the ARVC group (59/90, 65.6%) than in the idiopathic RVT group (4/90, 4.4%) or controls (1/162, 0.6%). The RV extent score in the ARVC group (53.0 +/- 24.8) was significantly higher than that in the idiopathic RVT group (8.4 +/- 10.1) or controls (1.2 +/- 4.9). The RV extent score correlated well with the regional RV perfusion score (P < 0.0001) and with the RV ejection fraction (P < 0.0001). Non-invasive RV perfusion mapping using a (99m)Tc-labelled tracer is useful for the quantitative evaluation of RV substrates in patients with ARVC.     

Apoptosis, necrosis and cell proliferation-inhibition by cyclosporine A in U937 cells (a human monocytic cell line).

The immunosuppressive drug cyclosporine A (CsA) has been used in both organ transplantation and the treatment of autoimmune disorders. However, the drug causes adverse effects in the kidney, liver and nervous system, characterized by cellular loss in the affected area. Apoptosis has been shown to play a role in CsA-induced cytotoxicity. Because permeabilization of the mitochondrial membrane is a common criterion in most apoptotic settings in vertebrate cells, here we evaluated whether CsA causes loss of mitochondrial function in the pathway leading to cellular cytotoxicity. We found that CsA caused a concentration- and time-dependent loss of cell viability in the U937 cell line. Treatment of cells at a dose of 10 microM CsA resulted in G0/G1 arrest with a concurrent decrease in the number of cells in the S and G2/M phases of the cell cycle. In mechanistic studies related to the loss of viability, treating cells with 10 microM CsA for 24 h resulted in both DNA fragmentation and an increase of annexin-V-positive cells. CsA treatment also increased activity of the cysteine protease caspase-3, decreased the mitochondrial membrane potential and induced the release of cytochrome c into the cytosol. Furthermore, CsA treatment increased the number of cells in the sub-G0/G1 peak, indicative of a reduction in DNA, although this increase was not observed when cells were pre-treated with a broad caspase inhibitor. In the study, we also found that a higher dose of CsA induces LDH release when the cells were incubated for a longer period. Taken together, these data suggest that the mode of cell death induced by CsA is dose- and time-dependent. Short-term incubation with lower doses of CsA arrests cell growth; this arrest overlaps with the occurrence of apoptosis and then with necrosis after longer treatment periods with higher doses of CsA.     

The enzymatic basis for the conversion of nonfucosylated to fucosylated alpha-fetoprotein by acyclic retinoid treatment in human hepatoma cells: activation of alpha1-6 fucosyltransferase.

The purpose of the present study was to investigate the mechanism by which nonfucosylated alpha-fetoprotein (AFP) is converted to fucosylated AFP in human hepatoma cell lines exposed to acyclic retinoid (AR), an effective drug for the secondary prevention of hepatocellular carcinoma. AR treatment (100 microM) of HepG2 and Hep3B cells significantly increased the activity and mRNA levels of alpha1-6 fucosyltransferase (alpha1-6 FucT), the enzyme responsible for the fucosylation of AFP, leading to an increase in fucosylated glycoproteins as evidenced by lectin binding measurements. Lectin immunoelectrophoresis of AFP obtained from culture media indicated that the relative percentage of nonfucosylated AFP (L1 fraction) was decreased and alpha1-6 fucosylated AFP (L3 fraction) was increased in these hepatoma cell lines after treatment with AR. The total AFP levels were, however, markedly suppressed by AR treatment, and therefore the absolute L3 fraction on the basis of the total AFP present was extremely low. These results demonstrate that AR enhances the conversion of the L1 to the L3 fraction due to the activation of alpha1-6 FucT in human hepatoma cell lines despite clinical outcome with AR treatment and the L3 fraction of AFP. Even though the dramatic decrease in AFP is the limiting factor in the synthesis of the L3 fraction and, therefore, the absolute value of fucosylated AFP is extremely low, the conversion from L1 to L3 as judged by lectin immunoelectrophoresis represents a good marker for the progress of AR treatment.     

FDG accumulation in aortic walls

A 65-year-old woman with no symptoms underwent whole-body F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for cancer screening. FDG accumulation was detected incidentally in her arterial walls, including the aortic wall. She had no history of inflammatory or cardiovascular disease. Although accumulation of FDG is well recognized in the aortic wall when vasculitis is present, this patient showed no symptoms of active vasculitis during the 22-month follow-up period after the PET study. The aortic wall might be a site where FDG accumulates physiologically in elderly persons.     

Comparison of image reconstruction algorithms in myocardial perfusion scintigraphy

The purpose of this study was to compare the clinical utility of two image reconstruction algorithms in myocardial perfusion SPECT (single-photon emission computed tomography): filtered back-projection (FBP) and ordered subset expectation maximization (OSEM). A rest/stress one-day protocol with 99mTc-MIBI or tetrofosmin was performed on 102 consecutive patients who underwent coronary angiography. After SPECT data acquisition, images were reconstructed with FBP and OSEM algorithms. We assessed diagnostic performance (sensitivity, specificity and accuracy) in detecting coronary artery stenosis and evaluated regional tracer uptake with a 4-point scoring system. Although there were no significant differences in diagnostic performance between FBP and OSEM reconstruction, the OSEM method yielded higher uptake in the RCA area than the FBP method by reducing the count-loss artifact due to hepatic uptake of the tracers. In addition, regional uptake in the LCX area was significantly lower in the OSEM image than in the FBP image; this phenomenon was observed mainly in patients with coronary stenosis and/or infarction in the LCX territory. In conclusion, OSEM and FBP offered comparable diagnostic performance in stress myocardial perfusion SPECT. The OSEM method contributed to reduction of the count-loss artifact in inferior and posterior walls and to easy recognition of hypoperfusion in the LCX area.     

Excision of a choledochal cyst and simultaneous hepatic lateral segmentectomy

We treated a 4-year-old girl with a choledochal cyst (CC) with bilateral intrahepatic involvement. A severe stricture between the enormously dilated left intrahepatic bile duct and the dilated common hepatic duct was found; this necessitated prophylactic hepatic lateral segmentectomy together with excision of the CC to avoid possible stone formation in the cystically dilated left intrahepatic duct. The choice of the combined procedures was based upon long-term results of other patients in our experience. This is the first such procedure to be reported.     

Application of positron emission tomography imaging to cancer screening

Whole-body positron emission tomography (PET) with(18)F-fluorodeoxyglucose (FDG) is a diagnostic modality that can noninvasively survey the entire body and sensitively detect various cancers. In this study, we examined the potential application of whole-body PET for cancer screening in asymptomatic individuals. PET was performed in conjunction with conventional examinations including physical examination, laboratory study, ultrasonography and chest computed tomography. Between September 1994 and March 1999, 3165 asymptomatic individuals participated in 5575 screening sessions (2017 men and 1148 women; mean +/- SD age, 52.2+/-10.4 years). Follow-up periods were no less than 10 months. PET results were compared with the screening outcomes. Within 1 year after screening, malignant tumours were discovered in 67 of the 3165 participants (2.1%). PET findings were true-positive in 36 of the 67 cancers (54%). Most of the 36 patients underwent potentially curative surgery; thus a wide variety of cancers were detected by PET at potentially curable stages. However, PET findings were false-negative in 31 of the 67 patients (46%). 14 of these 31 (45%) were of urological origin. FDG PET imaging has the potential to detect a wide variety of cancers at potentially curable stages. However, PET imaging is not suited to screening test of general population because PET examination involves substantial cost.     

Comparison of methotrexate resistance conferred by a mutated dihydrofolate reductase (DHFR) cDNA in two different retroviral vectors

We previously reported the protection of hematopoietic cells from methotrexate (MTX) toxicity using an N2-based double copy vector containing serine 31 (S31)-mutated dihydrofolate reductase (DHFR) (DC/SV6S31). To examine whether the use of SFG-based dicistronic vectors will lead to improvement in gene transfer over the DC/SV6 vector, we compared the protection provided by MTX to NIH3T3 cells and hematopoietic progenitor cells infected with these retroviral constructs containing the S31 variant DHFR cDNA. In NIH3T3 cells, the 50% effective dose values of MTX conferred by the SFG vector were 8-fold higher than those obtained with the DC/SV6 vector. DHFR mRNA levels were 22-fold and 38-fold higher than that seen for the DC/SV6 vector according to Northern blot and real-time polymerase chain reaction analysis, respectively. However, DHFR protein expression and DHFR enzyme activity were only 1.5-fold and 2-fold higher in the SFG vector, respectively, indicating that the mRNA from the SFG vector is translated less efficiently than the mRNA generated from the DC/SV6 vector. Furthermore, the degree of MTX protection conferred by each vector in both mouse and human hematopoietic cells was the same. These results indicate that the in vitro transduction efficiency and transgene expression of human DHFR in hematopoietic progenitor cells is equally conferred by both vectors.