Resistance of Copenhagen rats to chemical induction of glutathione S- transferase 7-7-positive liver foci

Copenhagen (Cop) rats are completely resistant to the chemical induction of mammary adenocarcinomas, but their susceptibility to hepatocarcinogenesis is virtually unknown. Rat liver is a well- characterized and easily manipulated tissue in which to study carcinogenesis. Therefore, if Cop rats are resistant to hepatocarcinogenesis, studies into resistance mechanisms may be feasible. Male Cop and F344 rats, 7-8 weeks old, were initiated using either N-nitrosodiethylamine (DEN) (200 mg/kg, i.p.) or a two-thirds partial hepatectomy (PH) followed by N-methyl-N-nitrosourea (MNU) (60 mg/kg, i.p.). The rats were then promoted using a modified resistant hepatocyte (RH) protocol (a combination of four doses of 2- acetylaminofluorene (2-AAF) and a single dose of CCl4 that provides a selective mitotic stimulus for initiated cells). Six weeks after initiation the rats were killed and liver sections were stained for glutathione S-transferase 7-7 (GST 7-7), a marker for putative preneoplastic hepatocytes. Cop rats were found to be highly resistant, having a approximately 9- and approximately 27-fold smaller percentage of liver area occupied by GST 7-7-positive foci than susceptible F344 rats following initiation by DEN and MNU respectively. Furthermore, gross liver nodules did not form in any of the Cop rats, whereas all F344 rat livers contained nodules. Hepatic necrosis caused by DEN during initiation, and CCl4 during promotion is necessary to stimulate compensatory hepatocyte division. We demonstrated that these agents do indeed increase serum transaminase levels and produce histologic evidence of necrosis in Cop rats. In order for liver foci to grow rapidly in the RH protocol, the surrounding normal hepatocytes must be mito-inhibited by 2-AAF. We found that the degree of mito-inhibition of normal hepatocytes by 2-AAF is the same in Cop and F344 rats. These results show that the Cop rat is highly resistant to the chemical induction of putative preneoplastic liver foci and nodules.      

Desmoplastic fibroma of the proximal ulna

A young man presented with desmoplastic fibroma in the proximal ulna. This rare tumour was treated by curettage and bone grafting.     

Trends in the incidence rates of tonsil and base of tongue cancer in England, 1985�C2006

INTRODUCTION

The aim of this study was to investigate whether incidence rates of tonsil and base of tongue cancer in England are increasing using data from the UK cancer registry.

SUBJECTS AND METHODS

Cancer registrations for oral cavity and oropharynx cancer from 1985–2006 in England were obtained from the National Cancer Information Service. Population estimates were obtained from the Office for National Statistics. Age-adjusted incidence rates and age-specific incidence rates were calculated. The sexes were considered separately as incidence rates are known to differ significantly between men and women. Linear regression was performed to establish whether there was a relationship between incidence rates and time.

RESULTS

There has been an increase in all oral cavity and oropharyngeal cancer in the study period. Linear regression analysis suggests that approximately 90% of the variance in age-adjusted incidence rates for men and women for tonsil, base of tongue and other oral cavity cancer is explained by the passage of time. For other oropharyngeal cancer, the variance is 62% and 46% in men and women, respectively. The estimated annual percentage change from 1985 to 2006 in age-adjusted incidence rates for tonsil and base of tongue cancer is 5.7% and 6.7% for men, and 4.3% and 6.5% for women, respectively.

CONCLUSIONS

This study confirms a wide-spread clinical impression that there has been an increase in age-adjusted incidence rates, between 1985 and 2006, in all oral cavity cancer in England. The age range 40–69 years has seen the biggest increases in age-specific incidence rates for tonsil and base of tongue cancer. This reflects the findings of similar studies in other countries.     

Inhibiting the complement system does not reduce injury in renal ischemia reperfusion.

The complex pathogenesis of ischemia reperfusion injury (IRI) includes endothelial expression of adhesion molecules, leukocyte recruitment and activation, reactive oxygen species production, and apoptotic and necrotic cell death. A role for complement in IRI of different organs, including kidney, has been proposed on the basis of results of experiments that used pharmacologic inhibitors as well as animals that were deficient in individual complement proteins. Here, renal IRI in mice was examined. Animals that were deficient in C3 had partial protection from IRI induced by 27.5 min of bilateral renal ischemia, followed by 20 h of reperfusion (blood urea nitrogen [BUN] values, 46.6 +/- 6.9 and 68.4 +/- 7.9 mg/dl in C3 -/- and C3 +/+ mice; n = 7 and 8, respectively; P = 0.033). Given the reduction in IRI in C3 -/- mice, it was investigated, by use of the rodent C3 convertase inhibitor CR1-related gene/protein y-Ig (Crry-Ig), whether exogenous administration of a complement inhibitor could lessen renal injury. Despite the use of Crry-Ig in high doses, there was no significant reduction of injury induced by 20 to 30 min of ischemia followed by up to 30 h of reperfusion. Histologic examination revealed acute tubular necrosis and neutrophilic infiltration, both of which correlated significantly with BUN values (P < 0.001). Of interest, C3 deposition around renal tubules was significantly less in animals with IRI, compared with that in unmanipulated controls (P < 0.001). In Crry-Ig-treated animals, C3 deposition was inversely proportional to BUN values (r = -0.63; P < 0.001), which presumably indicates that severe vascular IRI allowed access of the 160 kD Crry-Ig to the interstitium. Thus, renal IRI in mice may have a partial complement dependence, yet pharmacologic inhibition of the complement system does not seem to be effective, likely because of the presence of other mediator systems that operate in parallel.     

Pineal germinoma: MR imaging

Magnetic resonance (MR) imaging characteristics of pineal germinomas are described in seven patients imaged with MR and computed tomography (CT). In patients with symptoms of an enlarging process in the quadrigeminal plate cistern, MR imaging was as sensitive as CT scanning in detecting the mass. MR imaging did not detect a normal-sized, calcified neoplastic gland. Germinoma, germinoma with embryonal cell carcinoma elements, and pineoblastoma demonstrated different MR signal characteristics. Although direct coronal and sagittal MR images were useful in defining the relationship of the tumor to the posterior third ventricle, Sylvian aqueduct, and vein of Galen, the ease, rapidity, and sensitivity of CT scanning suggest that CT should remain the modality of choice for initial evaluation and screening of the pineal region, especially in the younger pediatric population, in whom detection of calcification may provide the only clue of an abnormality.     

Osteopetrosis: MR characteristics at 1.5 T

Four patients with proved osteopetrosis (three with the infantile malignant form and one with the benign form) were examined with magnetic resonance imaging at 1.5 T. All patients were studied in the coronal and sagittal planes using both short and long repetition time/echo time sequences. The infantile malignant form was characterized by a complete lack of signal from the marrow alternating with a signal intensity equivalent to that of the intervertebral disks, resulting in a "stepladder" appearance. In the benign form or after successful marrow transplantation in the infantile malignant form, intermediate or high signal intensity in the vertebrae was noted, suggesting the presence of some marrow elements.