Allelic loss on 17p13 (TP53) and allelic loss on 3p21 in early squamous cell carcinoma of the lung

Roentgenographically occult bronchogenic squamous cell carcinomas are early lung cancers that localize in the bronchial wall, and are thought to be a good model to elucidate the carcinogenesis of lung cancer. In the present study, we analyzed the incidence of allelic losses on chromosome regions 3p21 and 17p13 in 40 cases of roentgenographically occult bronchogenic squamous cell carcinomas, using three microsatellite dinucleotide polymorphic markers. We also investigated the relationship between such allelic loss and the clinicopathological findings of those cases. These chromosome regions showed frequent losses. Moreover, the incidence of loss on 17p13 increased gradually along with the advance of the depth of invasion, while the incidence of loss on 3p21 increased along with the advancing length of the longitudinal extension. These results suggested that these chromosome regions play different roles in lung cancer progression, i.e., the 3p21 chromosome region was related to the longitudinal extension of the carcinoma while the 17p13 (p53) region was related to the depth of invasion. Received: July 13, 1999 / Accepted: March 24, 2000     

Effects of N-acetylcysteine, quercetin, and phytic acid on spontaneous hepatic and renal lesions in LEC rats

The effects of anti-oxidants were examined in Long-Evans Cinnamon (LEC) rats, which develop acute hepatic injury, and subsequent hepatic and renal tumors due to accumulation of excess Cu. The rats, at the age of 15 weeks, were supplied a diet containing either 1% of N-acetylcysteine (NAC), quercetin (QC), or phytic acid (PA), or basal diet alone. At weeks 2 and 6 posttreatment, animals were sacrificed for collection of blood and tissue samples. In the NAC-treated group, the development of hepatic and renal lesions was dramatically reduced. In addition, accumulation of Cu and Fe in the liver was suppressed. Acrolein-modified protein, a new marker for lipid peroxidation, was not detected in the liver or kidney of NAC treated rats, even though deposition was evident in control. Neither QC nor PA affected the development of spontaneous hepatic lesions. These results indicate that oxidative stress was reduced by NAC in the liver and kidney, and suggest that Cu and Fe may be involved in the generation of oxidative stress in the liver. In addition, it was suggested that the different effects of the anti-oxidants on lesion development in LEC rats might be related to different mechanisms of action with regard to oxidative stress.     

Factors associated with serum high mobility group box 1 (HMGB1) levels in a general population

High mobility group box 1 (HMGB1), a nonhistone chromatin-associated protein, is implicated as a mediator of both infectious and non-infectious inflammatory conditions. Clinical research on this protein in humans just has begun; serum HMGB1 was reported to be elevated in a small number of critically ill patients suffering from sepsis. However, the kinetics, distribution and factors associated with circulating HMGB1 are unknown in a general population. In this study, we examined these issues in a large population of healthy subjects. Fasting blood samples were obtained from 626 subjects (237 males and 389 females). HMGB1 levels showed a skewed distribution with a mean of 1.65 ± 0.04 ng/ml. Multiple stepwise regression analyses found that white blood cell (WBC) counts (P = .016) and the soluble form of receptor for advanced glycation end products (sRAGE; P < .001, inversely), which is also known to be a receptor for HMGB1, were independently associated with HMGB1 levels. We demonstrated for the first time that circulating HMGB1 levels were inversely associated with sRAGE levels in a general population. Because RAGE is involved in HMGB1 signaling, our present study suggests that sRAGE may capture and eliminate circulating HMGB1 in humans.     

Effect of unilateral testicular rupture on histopathology and germ cell delayed-type hypersensitivity in C3H/He and A/J mice

Contralateral orchitis induced by unilateral testicular injury has been reported as sympathetic orchitis in men and experimental animals. In mice, experimental sympathetic orchitis (ESO) was first demonstrated in the C3H/He strain after experimental testicular trauma. Delayed-typed hypersensitivity (DTH) to testicular germ cells is induced by testicular trauma and treatment with cyclophosphamide before the trauma further enhances anti-testicular germ cell DTH. In the present study we investigated ESO induction with or without cyclophosphamide pretreatment in two murine strains, C3H/He and A/J mice, that are susceptible to testicular autoimmunity. The results show that traumatized testes undergo early degeneration of the seminiferous epithelium followed by neutrophilic inflammation and later fibrosis with little lymphocytic infiltration, in both murine strains. In the contralateral testes, ESO characterized by both lymphocytic inflammation and spermatogenic disturbance was induced in both strains. However, the incidence and severity of ESO in A/J mice tended to be higher than in C3H/He mice. In contrast, cyclophosphamide pretreatment significantly augmented both pathological stages of ESO and anti-testicular germ cell DTH in C3H/He mice, while those in A/J mice were fully developed by testicular rupture alone and were not further augmented by cyclophosphamide pretreatment. We conclude that A/J mice are more sensitive to trauma-induced testicular autoimmunity than C3H/He mice.     

Validation of the pepsinogen test method for gastric cancer screening using a follow-up study

Background  

Serum pepsinogen (PG) measurement has been used for gastric cancer screening since the 1990s. However, there are no reports comparing the screening validity of the PG test method with that of conventional X-ray examination directly in the same population, using a follow-up study.