Reference values for urinary steroids in Japanese newborn infants: gas chromatography/mass spectrometry in selected ion monitoring

Urinary steroid profile analysis using gas chromatography/mass spectrometry (GC/MS) has been reported for the diagnosis of abnormal steroidogenesis in newborn infants with some success. We tried to establish the reference values of 63 urinary steroids in Japanese newborn infant, using GC/MS in selected ion monitoring (SIM) that utilizes two characteristic mass ions for each steroid for definitive identification. We studied 36 healthy full-term newborn infants (1-56 days of age) on spot urine samples to define the reference values (mg/g creatinine, median and 10-90 percentile range) and to investigate the possible difference between daytime and nighttime levels. We also studied 23 healthy adult females (20-24 years of age) on 24-hour-urine for the comparison of the reference values of newborn infants. Fifty metabolites of DHEA, pregnenolone, 17-hydroxypregnenolone, androstenedione, progesterone, 17-hydroxyprogesterone, 21-deoxycortisone, corticosterone, 18-hydroxycorticosterone, aldosterone, 18-hydroxycortisol, 11-deoxycortisol, cortisone, cortisol, and estrogen in each infant were measurable without interference, but 13 metabolites of 11-hydroxyandrostenedione, pregnenolone, 11-deoxycorticosterone, corticosterone, 11-dehydrocorticosterone, 21-deoxycortisol, 11-deoxycortisol and cortisol were unmeasurable in each infant due to the interference of fetal cortex steroids as confirmed by abnormal peak area ratios of two mass ions. All 63 metabolites in each control adult were measurable without interference. 16alpha-, 16beta-, and 15beta-hydroxy metabolites of 3beta-hydroxy-5-en-steroids, and 6beta-, 18-hydroxy and 11-oxo-metabolites of corticosteroids were significantly higher in full-term newborn infants than those in adults as previously reported. Urinary steroids showed little circadian variation in the newborn infants, indicating that spot urine can substitute for 24-hour urine.     

Blockade of Rho/Rho-associated coiled coil-forming kinase signaling can prevent progression of hepatocellular carcinoma in matrix metalloproteinase-dependent manner

Aim:  There is growing evidence that the Rho/Rho-associated coiled coil-forming kinase (ROCK) signaling pathway is upregulated in tumors and plays a key role in cancer invasion and metastasis. Our aim was to test the anticancer effects of Rho/ROCK inhibitor, Y-27632, including possible mechanisms in a highly-metastasizing hepatocellular carcinoma (HCC) mouse model on its secretion of matrix metalloproteinase (MMP) and tumor progression.
Methods:  Following orthotopic implantation of CBO140C12 HCC tumor fragments into the liver of mice, the mice were randomly assigned to a Y-27632-treated group or control group. After treatment for 4 weeks, specimens were obtained to evaluate tumor size, metastases, and immunohistochemical findings. In vitro , we examined the effects of Y-27632 and RhoC siRNA on MMP-2 and -9 expressions, invasiveness, and apoptosis in cultured tumor cells.
Results:  Both RhoA and RhoC were upregulated in HCC-bearing livers, and Y-27632 significantly inhibited not only tumor growth and intrahepatic metastasis ( P  < 0.05), but also tumoral MMP-9 expression. Moreover, Y-27632 treatment resulted in large necrotic areas in tumors. In vitro , Y-27632 and RhoC siRNA reduced MMP-2 and -9 expressions, as well as the chemotactic migration of tumor cells dose-dependently, and increased apoptosis eight times.
Conclusion:  Y-27632 suppresses progression and limits the intrahepatic metastasis of established HCC. This could be linked to the decreased MMP expression and induction of apoptosis in tumor cells. Rho signaling may prove to be a productive target in anticancer therapy.     

Experimental study of a novel thermotherapy for hepatocellular carcinoma using a magnesium ferrite complex powder that produces heat under a magnetic field

BACKGROUND/AIMS: The anti-cancerous effect on hepatocellular carcinoma of a newly established form of thermotherapy, which uses an implant heating system, was evaluated. As a new material for application in hyperthermia, the authors developed a powder type Mg-ferrite complex that produces heat under a relatively low-power magnetic field. METHODOLOGY: This material suspended in Lipiodol was injected into tumors on the backs of mice that consisted of human hepatocellular carcinoma cells. Hyperthermia was performed by directing a magnetic charge on tumor-bearing mice that contained the Mg-ferrite complex. The temperature of the tumor was kept at 42-43 degrees C, while the magnetic field power ranged from 50 to 80G. RESULTS: A 10-min hyperthermia treatment was insufficiently effective against tumor growth. Systemic injection of doxorubicin (ADM) before hyperthermia appeared to enhance the anti-cancerous effect, but the difference was little and did not reach a statistically significant level (repeated measure analysis of variance). The anticancerous effect of hyperthermia for 15 minutes, in contrast, was marked. The nodules had almost completely disappeared by the end of the experiment. CONCLUSIONS: In conclusion, it is suggested that hyperthermotherapy using this newly developed Mg-ferrite complex might become an option for low-invasive therapy for advanced hepatocellular carcinoma in humans.     

Endobronchial lipoma: review of 64 cases reported in Japan

BACKGROUND: Several recent studies discuss bronchoscopic techniques for treating endobronchial lipoma, an extremely rare benign tumor. OBJECTIVES: To describe the epidemiology of endobronchial lipoma and to propose appropriate therapeutic policies for treating this tumor. METHODS: We reviewed 64 cases of endobronchial lipoma: 33 cases previously reported in 30 different articles, and 31 case reports presented at thoracic meetings in Japan. RESULTS: Of the 64 patients included in this study (50 male and 14 female; mean age, 60 years), 40 patients had endobronchial lipoma in the right lung and 23 patients had it in the left lung. The overwhelming majority of the tumors (n = 61) were found in the first three subdivisions of the tracheobronchial tree. Forty-eight patients (75%) were symptomatic, and their symptoms included cough, sputum, hemoptysis, elevated temperature, and dyspnea. Additionally, abnormal radiographic findings were reported for 51 patients (80%): 18 patients had atelectasis, 14 patients had infiltration or consolidation, 6 patients showed volume loss of the lung, and mass shadow was identified in 9 patients, and another abnormality including pleural effusion was found in 4 patients. Forty patients underwent surgical resection: 4 pneumonectomies, 24 lobectomies, 8 bilobectomies, and 4 resections by bronchotomy. Bronchoscopic resection was carried out in 17 cases: 7 cases by Nd-YAG laser, 5 cases by electrosurgical snaring forceps, and another 5 cases with a combined therapy using both procedures. CONCLUSIONS: Bronchoscopic resection should be considered as the first choice of treatment for endobronchial lipoma; however, surgical therapy is indicated for patients who show the possibility of a complicated malignant tumor, who have destructive peripheral lung disease, who have extrabronchial growth, or who may have technical difficulties during the bronchoscopic procedure.     

A novel mutation Lys273Glu in the cardiac troponin T gene shows high degree of penetrance and transition from hypertrophic to dilated cardiomyopathy.

Familial hypertrophic cardiomyopathy (HC) can be caused by mutations in 9 different genes encoding sarcomere proteins expressed in cardiac muscle. To date, only 13 different mutations in the cardiac troponin T (cTnT) gene have been reported to cause HC. Clinical characteristics and prognosis associated with mutations of this gene have not been well characterized owing to the small size and composition of affected families. The aim of this study was to determine the characteristic phenotype of patients with HC caused by a novel cTnT gene mutation, Lys273Glu. Two hundred Japanese probands with HC were screened for mutations in the cTnT gene. The Lys273Glu missense mutation was present in 9 persons from 2 unrelated pedigrees. They exhibited different cardiac morphologies: 1 had a dilated cardiomyopathy-like feature, 7 had left ventricular hypertrophy with normal left ventricular systolic function, and the 6 of them had asymmetric septal hypertrophy. A 1-year-old boy was not evaluated with echocardiography. The mean maximum wall thickness was 18.0 +/- 5.5 mm (range 8 to 24). There were 7 histories of sudden death in 1 of the 2 families. The Lys273Glu substitution in the cTnT gene shows a high degree of penetrance (100% in persons aged >20 years), a high incidence of sudden death, and a partial transition from hypertrophic to dilated cardiomyopathy. Because the location of a mutation appears to influence the development of a phenotype, we suggest that the precise definition of the disease-causing mutation can provide important prognostic information about affected members.