Long-term control of disseminated pleomorphic xanthoastrocytoma with anaplastic features by means of stereotactic irradiation

Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic neoplasm of the brain. Some PXAs are accompanied by anaplastic features and are difficult to manage because of frequent recurrences that lead to early death. No previous reports have demonstrated consistent efficacy of adjuvant radiotherapy or chemotherapy for this disease. We report a case of PXA with anaplastic features treated with stereotactic irradiation (STI) that resulted in long-term control of repeatedly recurring nodules throughout the neuraxis. A 47-year-old woman presented with an epileptic seizure due to a large tumor in the right frontal lobe. The tumor was resected and diagnosed as PXA with anaplastic features. Sixteen months later, a relapse at the primary site was noted and treated with stereotactic radiosurgery using Gamma Knife. Two years later, the patient developed a tumor nodule in the cervical spinal cord that histologically corresponded to a small-cell glioma with high cellularity and prominent MIB-1 (mindbomb homolog 1) labeling. In the following months, multiple nodular lesions appeared through-out the CNS, and STI was performed six times for eight intracranial lesions using Gamma Knife and twice using a linear accelerator, for three spinal cord lesions in total. All lesions treated with STI were well controlled, and the patient was free from symptomatic progression for 50 months. However, diffuse dissemination along the craniospinal axis eventually progressed, and she died 66 months after initial diagnosis. Autopsy showed that the nodules remained well demarcated from the surrounding nervous system tissue. STI may be an effective therapeutic tool for controlling nodular dissemination of PXA with anaplastic features.     

Aberrant promoter methylation in pleural fluid DNA for diagnosis of malignant pleural effusion

Accumulating evidence implicates epigenetic changes such as hypermethylation in carcinogenesis. We investigated whether DNA methylation of 5 tumor suppressor genes in pleural fluid samples could aid in diagnosis of malignant effusion. In samples from 47 patients with malignant pleural effusions and 34 with nonmalignant effusions, we used a methylation-specific polymerase chain reaction to detect aberrant hypermethylation of the promoters of the DNA repair gene O(6)-methylguanine-DNA methyltransferase (MGMT), p16(INK4a), ras association domain family 1A (RASSF1A), apoptosis-related genes, death-associated protein kinase (DAPK), and retinoic acid receptor beta (RARbeta). Promoter hypermethylation was associated with malignant effusion for MGMT (Odds ratio (OR) = infinity), p16(INK4a) (OR = infinity), RASSF1A (OR = 13.8; CI, 1.71-112), and RARbeta (OR = 3.17; CI, 1.10-9.11), but not for DAPK. Instead, DAPK methylation was associated with the length of smoking (p < 0.05). Patients with hypermethylation of MGMT, p16(INK4a), RASSF1A or RARbeta were 5.68 times more likely to have malignant effusions than patients without methylation (p = 0.008). Methylations per patient were more numerous for lung cancer than nonmalignant pulmonary disease (0.915 vs. 0.206, p < 0.001). Sensitivity, specificity, and positive predictive value of methylation in one or more genes for diagnosis of malignant effusion were 59.6%, 79.4%, and 80.0% respectively. In conclusion, aberrant promoter methylation of tumor suppressor genes in pleural fluid DNA could be a valuable diagnostic marker for malignant pleural effusion.     

α-Hydroperoxy diethyl peroxide, an unusual natural compound isolated from an ascidian (Phallusia mammillata): acute toxicity in DDY mice

α-Hydroperoxy diethyl peroxide, a novel compound found in the tunic of ascidians, has two peroxide moieties per molecule. Since ascidians are a widely served food item in Japan, human exposure to this compound potentially exists in the seafood preparation industries. No toxicological data have so far been published on this compound, and so we determined the intraperitoneal 6-day LD₅₀ in mice and conducted histopathological examinations. The 6-day LD₅₀, was found to be 199 with 95% confidence limits of 126–314 . Histopathological examination revealed necrosis induced in a variety of cells that had been directly exposed to the compound. These cells included hepatocytes, parenchymal pancreatic cells and fat cells. It is concluded that direct contact with this compound is likely to elicit cellular necrosis of various organs. The specific toxicological effects are probably dependent on the route of exposure.     

Dietary modification of metabolism and toxicity of chemical substances—with special reference to carbohydrate

Rats were fed various test diets only on the day before sacrifice or every day for 3 weeks prior to sacrifice in order to assess the effects of protein (casein), fat (a mixture of olive and corn oils) and carbohydrate (sucrose) on the liver mixed-function oxidase activity. The activity was determined by measuring metabolic rates of 8 volatile hydrocarbons, i.e., benzene, toluene, styrene, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethylene, and trichloroethylene. Contrary to the general belief, it was found that carbohydrate, not protein or fat, regulates the metabolism of these hydrocarbons: a diet which was deficient in carbohydrate remarkably enhanced the metabolism irrespective of protein and fat contents in the diet. This conclusion was confirmed by employing two types of diet, one in which the carbohydrate was replaced by an isocaloric amount of protein or fat (thus keeping total calories of each diet constant) and the other in which the carbohydrate content was varied with protein and fat contents fixed (total calories of each diet differed from others according to the carbohydrate content). In accordance with this, dietary carbohydrate intake also exerted a remarkable influence on the hepatotoxicity of carbon tetrachloride which needs to be metabolically activated to become cytotoxic: the smaller the intake, the more severe the liver injury.     

Protein expression pattern of collagen type XV in mouse cornea

Purpose To examine the alteration of protein expression pattern of collagen type XV in cornea during embryonic development and adult tissue repair. Collagen type XV is a basement membrane collagen of a subfamily of multiplexins (multiple triple helix domains and interruptions). Its COOH-terminal peptide has an anti-angiogenic effect and its distribution in avascular tissue of cornea is of interest.Methods Eyes of mouse embryos [day (E) 10.5–18.5] and healing adult mouse corneas following either débridement injury or incision were embedded in paraffin. Deparaffinized sections were processed for immunofluorescent staining with anti-collagen XV antibody.Results At E14.5 embryonic corneal epithelium, as well as fibroblasts in eyelids, began to express this collagen type very faintly, and at E18.5, besides corneal epithelial expression, epidermis, palpebral conjunctiva, and keratocytes started to express collagen type XV. In adult mouse cornea, collagen type XV was observed in basal and suprabasal epithelial cells and stroma, but not in the subepithelial basement membrane. Healing epithelial cells following débridement or incision injury down-regulated its protein expression.Conclusions Mouse embryonic corneal epithelium and keratocytes begin to express collagen type XV before birth. Healing murine corneal epithelium down-regulates collagen XV expression. The presence of collagen XV in corneal stroma may play a part in avascularity.     

Reference birthweight for multiple births in Japan

PURPOSE: Intrauterine growth curves of twins, that is, birth weights according to gestational age, were calculated from birth certificate data. METHODS: Multiple births were identified by birthplace, ages of the parents, gestational age, and year and month of birth. There were 49,240 twin births in Japan between 1988 and 1991. Of these, 32,232 livebirth-livebirth pairs, 679 livebirth-stillbirth pairs, and 278 stillbirth-livebirth pairs were included in this analysis. There were also 1894 triplet live births from 744 sets of triplets and 206 quadruplet live births analyzed. For all, access was made to the database of birth certificates in the form of magnetic tapes giving birthweights in hundred gram categories. RESULTS: For all gestational ages, median birthweights of males were ca. 0.05 kg-0.1 kg larger than female values. Compared to singleton births in Japan, median birthweights of twins remained ca. 0.15 kg smaller until gestational age of 34 weeks, the difference then increasing to ca. 0.5 kg at 42 weeks of gestation. As for birth order, mean birthweight of the first twin was larger than that of the second and the standard deviation was larger for the second. Birthweights of twins from multiparous mothers were greater than those from primiparous mothers. Among the multiple births, median birthweight for gestational age was found to be greatest in twins, lower in triplets and lowest in quadruplets. In triplets, the 50th centile for boys was 0.08 kg larger than for girls. DISCUSSION: With regard to perinatal growth, the fetus is affected more or less by the limitation of uterine expansion in the late gestational weeks. Reference birthweights for exclusive use for multiple births are different from that for singletons.     

Design and synthesis of the potent,orally available,brain-penetrable arylpyrazole class of neuropeptide Y5 receptor antagonists

Novel arylpyrazole derivatives were synthesized and evaluated as neuropeptide Y (NPY) Y5 receptor antagonists. Compound (-)-7, which features a novel chiral 2,3-dihydro-1H-cyclopenta[a]naphthalene moiety, showed good binding affinity and antagonistic activity for the Y5 receptor. After intracerebroventricular administration in SD rats, (-)-7 significantly inhibited food intake that was induced by the centrally administered Y5-preferring agonist, bovine pancreatic polypeptide, but had only a negligible effect on NPY-induced feeding.     

Active smoking, passive smoking, and breast cancer risk: findings from the Japan Collaborative Cohort Study for Evaluation of Cancer Risk

Background

Evidence is lacking regarding the relationship between cigarette smoking and breast cancer in Japanese women. We examined the association between breast cancer incidence and active and passive smoking in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk.

Methods

Our study comprised 34,401 women aged 40-79 years who had not been diagnosed previously with breast cancer and who provided information on smoking status at baseline (1988-1990). The subjects were followed from enrollment until December 31, 2001. Cox proportional-hazards models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between breast cancer incidence and tobacco smoke.

Results

During 271,412 person-years of follow-up, we identified 208 incident cases of breast cancer. Active smoking did not increase the risk of breast cancer, with a HR for current smokers of 0.67 (95% CI: 0.32-1.38). Furthermore, an increased risk of breast cancer was not observed in current smokers who smoked a greater number of cigarettes each day. Overall, passive smoking at home or in public spaces was also not associated with an increased risk of breast cancer among nonsmokers. Women who reported passive smoking during childhood had a statistically insignificant increase in risk (HR: 1.24; 95% CI: 0.84-1.85), compared with those who had not been exposed during this time.

Conclusion

Smoking may not be associated with an increased risk of breast cancer in this cohort of Japanese women.Key words: Smoking, Breast Neoplasms, Risk, Cohort Studies     

The relation between superoxide dismutase in cancer tissue and clinico pathological features in breast cancer

The localization of Cu/Zn- and Mn-superoxide dismutase (SOD) in breast cancer tissue (12 papillotubular carcinomas, 21 solid-tubular carcinomas, 16 scirrhous carcinomas, 1 medullary carcinoma, 1 secreting carcinoma, 1 lobular carcinoma, 1 Paget's disease) was investigated via an immunohistochemical technique using antihuman Cu/Zn- and Mn-SOD antibodies in 10%formalin fixed-paraffin embedded thin sections. Both SODs stained strongly in the normal breast gland, but not clearly in many cancer tissues. Furthermore, Cu/Zn-SOD stained more strongly in well differentiated tubular carcinomas than in poorly differentiated tubular carcinomas. It tended to stain less in tumors which recurred or had a poor outcome, and in tumors with a diploid pattern on DNA flow cytometry. Mn-SOD staining was similar to that of Cu/Zn-SOD, but no significant differences among subgroups was found, since the incidence of positively staining tumors was too small in all groups. The intensity of SOD staining seems to change in relation to cell proliferation and differentiation in breast carcinoma, and may be a prognostic indicator, since SOD decreased in poorly differentiated carcinoma and in tumors which developed distant metastasis. Thus, the localization of SOD in breast cancer tissue can provide useful information for cancer treatment.