P53 Gene Mutations in Pituitary Carcinomas

Although p53 overexpression detected by immunohistochemistry has been reported in pituitary adenomas and carcinomas, genetic mutations in the p53 gene have not been previously detected in these tumors. We analyzed a series of eight pituitary adenomas and six pituitary carcinomas by immunohistochemistry, polymerase chain reaction amplification, and sequencing of p53 exon 5 through exon 8 for genetic mutations. Three carcinomas showed more than 20% expression of p53 protein in the tumor cells. One of these tumors with 60% overexpression of p53 protein had a mutation in codon 248, a common “hot spot” for p53 mutation, while the other carcinoma with 90% overexpression of p53 protein had a mutation in codon 135. All adenomas were negative for p53 mutations and had 15% of the cells expressing the p53 protein. Analysis of control tumors including four lung carcinomas with proven p53 mutations also had greater than 85% of the tumor cells overexpressing p53 protein. Two breast carcinoma cell lines with known p53 mutations, MBA-MD 231 and MBA-MD-486, also showed greater than 85% of the tumor cells overexpressing p53. These results show that p53 mutations are present in a subset of pituitary carcinomas and are usually associated with a high percentage of tumor cells overexpressing the p53 protein.     

CAPP-seq analysis of circulating tumor DNA from patients with EGFR T790M–positive lung cancer after osimertinib

International Journal of Clinical Oncology - We here applied cancer personalized profiling by deep sequencing (CAPP-seq) to analysis of circulating tumor DNA (ctDNA) to identify resistance...     

Effects of dietary supplementation with n-3 fatty acids compared with n-6 fatty acids on bronchial asthma

OBJECTIVE: The effects of perilla seed oil (n-3 fatty acids) on bronchial asthma were compared with the effects of corn oil (n-6 fatty acids) in relation to the pulmonary function and the generation of leukotriene B4 (LTB4) and C4 (LTC4) by leucocytes. METHODS AND SUBJECTS: 14 asthmatic subjects were divided randomly into two groups: one group (7 subjects) consumed perilla seed oil-rich supplementation and the other group (7 subjects) consumed corn oil-rich supplementation for 4 weeks. Generation of LTs by leucocytes and respiratory function were compared between the two groups. RESULTS: The generation of LTB4 and LTC4 by leucocytes tended to increase in subjects (N=7) with corn oil-rich supplementation, and decrease in subjects (N=7) with perilla seed oil-rich supplementation. Significant differences between the two groups were observed in the generation of LTB4 at 2 weeks (p<0.05) and LTC4 at 2 weeks (p<0.05) after dietary supplementation. Significant increases in the value of PEF (p<0.05), FVC (p<0.01), FEV(1.0) (p<0.05) and V(25) (p<0.05) were found in subjects who received perilla seed oil supplementation for 4 weeks. And significant differences in the value of FVC (p<0.05) and FEV(1.0) (p<0.05) were observed between the two groups after 4 weeks of dietary supplementation. CONCLUSION: These results suggest that perilla seed oil-rich supplementation is useful for the treatment of asthma in terms of suppression of LTB4 and LTC4 generation by leucocytes, and improvement of pulmonary function.     

Detection of angiotensin-converting enzyme gene insertion/deletion polymorphism from paraffin-embedded tissues: the Hisayama study.

Previous studies have suggested that archival materials from formalin-fixed paraffin-embedded blocks are unsuitable for most molecular techniques because the extracted DNA can be severely degraded. Therefore, the present study was designed to investigate the accuracy of genotyping for the insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene from paraffin-embedded tissues of autopsy cases from Hisayama Town, Japan. The genotype was determined using the double polymerase chain reaction method and to test the accuracy of the method, the polymorphism was investigated using paraffin-embedded tissues from 18 cases whose ACE genotypes (6 cases for each genotype) were known in advance from analysis of fresh-frozen tissue samples. Genotyping using paraffin-embedded tissues was then determined for 968 autopsy subjects. The genotype could be determined in 16 of the 18 test samples (88.9%) and there was no discrepancy with the results obtained from the fresh-frozen tissues. Of the 968 autopsy cases, the frequency of the DD, ID, and II genotypes was 12.4%, 47.3%, and 40.3%, respectively, a distribution that did not deviate from the Hardy-Weinberg equilibrium (chi(22df )= 0.67, p=0.72). These findings suggest the accuracy of the present method of ACE genotyping from paraffin-embedded tissues.     

Disease-associated CIAS1 mutations induce monocyte death, revealing low-level mosaicism in mutation-negative cryopyrin-associated periodic syndrome patients

Cryopyrin-associated periodic syndrome (CAPS) is a spectrum of systemic autoinflammatory disorders in which the majority of patients have mutations in the cold-induced autoinflammatory syndrome (CIAS)1 gene. Despite having indistinguishable clinical features, some patients lack CIAS1 mutations by conventional nucleotide sequencing. We recently reported a CAPS patient with mosaicism of mutant CIAS1, and raised the possibility that CIAS1 mutations were overlooked in "mutation-negative" patients, due to a low frequency of mosaicism. To determine whether there were latent mutant cells in "mutation-negative" patients, we sought to identify mutation-associated biologic phenotypes of patients' monocytes. We found that lipopolysaccharide selectively induced necrosis-like cell death in monocytes bearing CIAS1 mutations. Monocyte death correlated with CIAS1 up-regulation, was dependent on cathepsin B, and was independent of caspase-1. Cell death was intrinsic to CIAS1-mutated monocytes, was not mediated by the inflammatory milieu, and was independent of disease severity or anti-IL-1 therapy. By collecting dying monocytes after lipopolysaccharide treatment, we succeeded in enriching CIAS1-mutant monocytes and identifying low-level CIAS1-mosaicism in 3 of 4 "mutation-negative" CAPS patients. Our findings reveal a novel effect of CIAS1 mutations in promoting necrosis-like cell death, and demonstrate that CIAS1 mosaicism plays an important role in mutation-negative CAPS patients.     

Role of central nicotinic and β-adrenergic receptors in the onset and further development of tail-tremor induced by repeated nicotine administration to rats

The effects of nicotinic and β-adrenergic receptor antagonists on tail-tremor induced by repeated nicotine administration were investigated in rats. The daily administration of nicotine (0.5mg/kg/day, s.c.) for 8 days resulted in an augmentation of tail-tremor. However, repeated administration of dimethyl phenyl piperazinium iodide (1mg/kg/day, s.c.) for 8 days did not cause tail-tremor. Mecamylamine (0.5mg/kg, i.p), administered before the nicotine injection on each day, abolished the tail-tremor. After discontinuation of the mecamylamine treatment, nicotine injections caused tail-tremor augmentation. Propranolol (20mg/kg, i.p.), administered before the nicotine on each day, suppressed the appearance of tail-tremor. After the discontinuation of propranolol treatment, the degree of tail-tremor induced by a single injection of nicotine on day 9 was much greater in the propranolol-treated group than in the saline-treated control group. Neither carteolol (20mg/kg, i.p.) nor metoprolol (20mg/kg, i.p.) treatment showed such effects. Intraspinal injection of 6-hydroxydopamine markedly enhanced the tail-tremor induced on the first day of nicotine injection. This effect became more intense on subsequent administration of nicotine. The enhanced tail-tremor following 6-hydroxydopamine treatment was abolished by mecamylamine (0.5 and 1mg/kg, i.p.), and was suppressed by propranolol (5–20mg/kg, s.c.) in a dose-dependent manner. These results suggest that central nicotinic receptors are essential for the onset and for the further development of tail-tremor induced by the repeated administration of nicotine, and that β₂-adrenoceptors are associated with the tremor mechanism. Moreover, spinal noradrenergic mechanisms may be involved in the manifestation of this phenomenon. Received: 18 June 1996 / Accepted: 15 December 1996     

Stomach-preserving gastric bypass for unresectable pancreatic cancer

From 1992 to 1995, we treated 25 patients who had unresectable pancreatic cancer witha stomach-preserving gastric bypass (SPGB). After as much of the stomach as possible was preserved, it was bypassed to the jejunum by end-to-side anastomosis. During the same period, five patients underwent other types ofbypasses while 47similar patients did not undergo gastric bypass. Althoughthe mean operative time for SPGB was significantly longer than for other types of bypass,the mean intraoperative blood loss was similar. Operative morbidity with SPGB was 28%, and there were no operative deaths. In patients undergoing SPGB, the incidence of delayed gastric emptying was high (24%), but the comfort index (ratio of duration of good palliation to duration of survival) exceeded 50% when metastases wereeither regional or systemic but limited. The comfort index of patients undergoing other types of bypass or not undergoing bypass was less than 40%. However,the patients with extensive systemic metastases survived less than 100 days and the comfort index was less than 30%for all treatment groups. Our resultsthus suggest that SPGB is safe and effective for patients witheither regional metastases or limited systemic metastases.     

Prediction of prognosis in open-heart-surgery by regional difference in leg surface temperature.

Change of the surface temperature of the leg during open-heart-surgery was determined in five patients, in whom either side of the femoral artery was ligated for cannulation. While the surface temperature at the patella was least influenced, that at the ankle paralleled closely the changes in the core body temperature and blood supply to the leg. Their difference (P-A difference) was studied to see if they can be used to predict prognosis of patients undergoing open-heart surgery. The P-A difference was followed for several hours after the open-heart surgery. It was marked positive when the surface temperature at the patella was higher than that at the ankle. Total of 54 patients were studied. Only one out of 29 patients with negative P-A difference succumbed. This is in sharp contrast to the 25 remaining patients with positive P-A difference, from whom as many as 12 died. In addition, the postoperative course of the 13 survivors from the latter group was more eventful. Since P-A difference seemed to indicate accurately cardiac output by reflecting the state of the peripheral circulation, it can be used as a useful parameter in prediction of the prognosis in open-heart surgery.