Significance of overexpression of metallothionein in mouse urinary bladder focal lesions induced by treatment with N-butyl-N-(4-hydroxybutyl)-nitrosamine

Metallothionein (MT) is expressed in various types of human tumors, including transitional cell carcinomas of the urinary bladder, but its biological significance remains unclear. In the present study, the role of MT in urinary bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) treatment was investigated using C57BL/6 mice. One hundred 5-week-old male C57BL/6 mice were divided into two groups, which were given drinking water with or without 0.05% BBN throughout the experimental period. Subgroups of ten animals from each group were sacrificed at weeks 5, 10, 15, 20 and 25, and urinary bladder samples were examined immunohistochemically for MT, proliferating cell nuclear antigen (PCNA) and apoptosis. MT was found to be abundant in normal-looking mucosa, but decreased with progression from precancerous lesions to invasive carcinoma in the urinary bladder obtained from BBN-treated mice. Lesions could be divided into MT-positive and negative. There was a tendency for greater MT expression in PCNA-positive lesions, while apoptosis was rather associated with MT-negativity. These data suggest that the overexpression of MT may play a role in mouse urinary bladder carcinogenesis.     

Clinical efficacy of bisphosphonate therapy for bone metastasis from breast cancer

Bisphosphonates inhibit osteoclastic bone resorption and are being used as treatment for bone metastases from breast cancer. Intravenous bisphosphonate therapy can significantly reduce skeletal related events (SREs) when administered concurrently with chemotherapy or endocrine therapy. In addition, intravenous bisphosphonate monotherapy is also able to alleviate cancer induced bone pain, and to improve bone metastases in some patients. Oral bisphosphonates are not routinely used for the treatment of bone metastases due to their low bioavailability. However, minodronate, a bisphosphonate 100-fold more potent than pamidronate, is now in phase II clinical studies in Japan, and may alter the role of oral bisphosphonates in the treatment of bone metastasis from breast cancer. The ASCO guidelines recommend that patients with osteolytic bone metastases be treated not with bisphosphonate monotherapy, but with concurrent bisphosphonate and systemic therapy. In addition, it is also recommended that current standards of care for cancer pain, analgesics and radiotherapy, should not be replaced with bisphosphonate therapy.     

Quantitative determination,by real-time reverse transcription polymerase chain reaction,of aromatase mRNA in invasive ductal carcinoma of the breast

Background

Estrogen is a mitogenic factor that is implicated in the genesis and progression of breast cancer via its binding to estrogen receptor (ER)-α. Synthesis of estrogen in situ is believed to be catalyzed mainly by aromatase. Previous studies comparing the relative contributions from tumor cells and stromal cells to local estrogen synthesis, as assessed by immunohistochemical analysis, were quite controversial and no consistent relationship was found between the presence of aromatase and any clinicopathologic factor. In addition, previous studies into aromatase gene expression and clinicopathologic factors are limited.

Methods

We assessed the level of expression of aromatase mRNA, using quantitative real-time RT-PCR, in 162 cases of invasive ductal carcinoma of the breast. Associations between aromatase expression and different clinicopathologic factors were sought.

Results

It was found that aromatase mRNA was expressed at significantly higher levels in patients older than 50 years, in those without axillary lymph node involvement, in those with tumor size less than 2 cm, and in ER-α positive tumors. However, no relationship was found between aromatase mRNA expression and any other clinicopathologic factor, including histologic grade and progesterone receptor status. Patients with high levels of expression of aromatase mRNA tended to have a better prognosis than did those patients with low expression.

Conclusion

These findings imply that ER-α and aromatase may be coexpressed in endocrine responsive patients. They may also indicate that aromatase expression could be a marker of endocrine responsiveness, and it may have prognostic implications for breast cancer progression.

     

Virtual pancreatoscopy of pancreatic cancer

BACKGROUND/AIMS: Virtual endoscopy is a new method of diagnosis using computer processing of three-dimensional images data sets. However, there are few reports about the clinical application of virtual endoscopy for the pancreas. In this study, we evaluated the feasibility of surface-rendered magnetic resonance virtual endoscopy for pancreatic cancer. METHODOLOGY: Twenty-six cases of pancreatic cancer were studied. Fifteen patients had pancreatic head cancer, 7 had pancreatic body cancer, and 4 had pancreatic tail cancer. Twelve patients underwent surgical resection of the pancreas. Magnetic resonance imaging data were acquired with a 1.5-T clinical imager (Signal.5; GE Medical Systems, USA). We used a multislab single-shot fast spin-echo sequence. Section thickness was between 2 and 3 mm in the coronal plane. Three-dimensional reconstructed images and virtual endoscopic images were generated with Advantage Windows by GE. RESULTS: Virtual endoscopic images could be generated in 20 patients with pancreatic cancer (76.9%). In these cases, we were able to observe the inner surface of the pancreatic duct and the stricture from not only the pancreatic head but also the pancreatic tail. Clear virtual images could not be generated in 6 cases. We were able to divide the 20 cases in which images could be generated into groups according to the appearance of the stricture. The edge of the stricture appeared to be protruding in 4 cases (15.4%), and appeared to be polygonal in 13 cases (50.0%). In 3 cases, we recognized the existence of a stricture, but the detail of the stricture was unclear. CONCLUSIONS: Virtual endoscopy caused minimal discomfort compared to real endoscopic examination, and it can access cystic lesions and the pancreatic duct behind the stricture. It is concluded that virtual endoscopy for pancreatic cancer has potential clinical utility.     

Successful Laparoscopic Right Gastroepiploic Aneurysmectomy: Report of a Case

A 75-year-old woman presented with a pulsatile, movable mass, about 5cm in diameter, in her lower abdomen. Abdominal ultrasonography revealed a circular mass with a variable hypo- and isoechoic border and a hypoechoic center. Color Doppler echography showed blood flow in the hypoechoic center, which was strongly enhanced on contrast-enhanced computed tomography. Based on these findings, we diagnosed a splanchnic artery aneurysm; however, celiac arteriography, performed twice, could not definitively identify it. An operation was performed under the tentative diagnosis of an aneurysm of the superior mesenteric artery or the gastroepiploic artery. On laparoscopic exploration, a globe-shaped mass, about 5cm in diameter, was found in the right side of the greater omentum, which was diagnosed as an aneurysm of the right gastroepiploic artery. We resected the aneurysm laparoscopically and the patient had an uneventful postoperative course. Thus, laparoscopic surgery was effective for this patient who required no vascular reconstruction.     

Differential contribution of three mitogen-activated protein kinases to PDGF-BB-induced mesangial cell proliferation and gene expression

This study examined the role of mitogen-activated protein (MAP) kinase in PDGF-BB-induced proliferation and gene expression of human mesangial cells (MC). PDGF-BB stimulation of MC increased mRNA for transforming growth factor-beta1 (TGF-beta1), monocyte chemoattractant protein-1 (MCP-1), and plasminogen activator inhibitor-1 (PAI-1) and increased the cell numbers. To inhibit activation of extracellular signal-regulated kinase (ERK), c-Jun amino-terminal kinase (JNK), and p38, MC were infected with recombinant adenovirus containing dominant-negative mutants of ERK, JNK, and p38 (Ad-DN-ERK, Ad-DN-JNK, Ad-DN-p38, respectively), respectively. Infection of MC with Ad-DN-ERK or Ad-DN-JNK inhibited PDGF-BB-induced increase in [(3)H]thymidine incorporation and cell numbers, whereas Ad-DN-p38 did not. Ad-DN-ERK inhibited MCP-1 and PAI-1 mRNA expression in MC, but not TGF-beta1. Ad-DN-JNK and Ad-DN-p38 inhibited TGF-beta1 and MCP-1 mRNA expression, but not PAI-1. The inhibition of activator protein-1 (AP-1) in MC, by adenovirus containing dominant-negative mutant of c-Jun (Ad-DN-c-Jun), inhibited PDGF-BB-induced cell proliferation and TGF-beta1, MCP-1, and PAI-1 expressions. Furthermore, Ad-DN-JNK or Ad-DN-p38, but not Ad-DN-ERK, attenuated PDGF-BB-induced AP-1 activation in MC, indicating the involvement of JNK and p38 in AP-1 activation. Our results indicated that ERK and JNK, but not p38, participated in PDGF-BB-induced MC proliferation. PDGF-BB-induced expression of TGF-beta1 was mediated by JNK and p38, MCP-1 expression was through ERK, JNK, and p38, whereas PAI-1 expression was due to only ERK. AP-1 activation, which was partially due to JNK and p38 activations, was involved in MC proliferation and these three gene expressions. Thus, three MAP kinases seem to contribute to progression of glomerular disease via different molecular mechanisms.     

Unruptured intracranial aneurysms in haemodialysis patients

SUMMARY:   While the mortality rate of subarachnoid haemorrhage is very high in haemodialysis (HD) patients, the prevalence of unruptured intracranial aneurysms in HD patients has not yet been elucidated. We performed cerebral magnetic resonance angiography (MRA) on 123 HD patients who did not have symptomatic cerebrovascular disease, and on 52 control subjects. On the basis of these images, the prevalence of unruptured intracranial aneurysms was evaluated. Unruptured aneurysms were found in three HD patients (2.4%). There were no aneurysms found in the healthy control group. There was no significant difference in the prevalence of unruptured aneurysms between HD patients and healthy controls. Therefore, the incidence of intracranial aneurysms is not associated with chronic renal failure.     

Leigh syndrome associated with West syndrome

Leigh syndrome (LS) (sub-acute necrotizing encephalomyelopathy) is characterized by symmetric brain lesions occurring mainly in the basal ganglia and associated with variable clinical manifestations such as hypotonia, psychomotor retardation, and feeding difficulties. Patients with LS may develop seizures. Only three patients with LS have been identified in the literature as having West syndrome (WS). We have seen 12 children with LS in the past 20 years, and noticed that as many as five of them developed WS. This report discusses five LS children with WS, comparing them with seven LS children without WS. In all five patients, infantile spasms developed after LS had become evident, in addition to other type(s) of seizures. The onset of LS in all the patients with WS was before 10 months of age. Although not statistically proven, early onset of LS, spasticity, nystagmus, apnea, poor feeding, and cardiac problems seemed to be associated with the development of WS. We were not able to conclude that certain types of symptoms or examination results of patients with LS indicated the development of WS. The association of LS with WS did not markedly influence the prognoses of the children. WS may not be a rare complication of LS, especially in infants under 12 months of age. This report is the first review of LS associated with WS.     

Primary progressive aphasia: diagnosis, varieties, evolution.

A referred cohort of 67 clinically defined PPA patients were compared to 99 AD patients with formal language and nonverbal cognitive tests in a case control design. Language fluency was determined at the first and last follow up visits. Quantitation of sulcal and ventricular atrophy on MRI was carried out in 46 PPA and 53 AD patients. Most PPA patients (57%) are relatively fluent when first examined. Visuospatial and memory functions are initially preserved. Aphemic, stuttering, "pure motor" presentation, or agrammatic aphasia are seen less frequently. Later most PPAs become logopenic and nonfluent, even those with semantic aphasia (dementia). In contrast, AD patients were more fluent and had relatively lower comprehension, but better overall language performance. MRI showed significant left sided atrophy in most PPA patients. Subsequent to PPA, 25 patients developed behavioral manifestations of frontotemporal dementia and 15 the corticobasal degeneration syndrome, indicating the substantial clinical overlap of these conditions. Language testing, particularly fluency scores supported by neuroimaging are helpful differentiating PPA from AD. The fluent-nonfluent dichotomy in PPA is mostly stage related. The aphemic-logopenic-agrammatic and semantic distinction is useful, but the outcomes converge.