A novel peptide (Thx) homing to non-small cell lung cancer identified by ex vivo phage display.

AIM: To identify linear peptide homing to non-small cell lung cancer (NSCLC) tumor cells using ex vivo phage display method. MATERIALS AND METHODS: Twenty-six clinical patient samples were used to identify linear homing peptide, which was exposed to NSCLC cell cultures and control cell lines to determine cell binding affinity and cell localization. Also, ex vivo biodistribution was analyzed using tumor-bearing mice. RESULTS: The panning yielded peptide enrichment with a core motif (A)/SRXPXXX. Based on this, an amino acid sequence, ARRPKLD, was selected for characterization and named Thx-peptide. The in vitro binding properties of Thx-peptide demonstrated selectivity toward NSCLC. Internalization assays showed that Thx-Alexa and fluorescein conjugates were located in a subset of perinuclearly located lysosomes of tumor cells. Thx-peptide appeared with fluorescein-labeled peptide and peptide-DTPA-chelator complex in adenocarcinoma xenografts in mice. CONCLUSION: Thx shows promise for targeted imaging and drug delivery.

Proliferative and anti-apoptotic activity of esophageal mucosa in gastroesophageal reflux disease is not affected by fundoplication: a 4-year follow-up study.

BACKGROUND: The role of fundoplication in the prevention of esophageal adenocarcinoma is controversial. Development of cancer is associated with proliferation and anti-apoptosis, for which little data exist regarding their response to fundoplication. METHODS: Ki-67 and Bcl-2 expression was assessed in the esophagogastric junction (EGJ) and the distal and proximal esophagus of 20 patients with gastroesophageal reflux disease (GERD) treated by fundoplication and in 7 controls. Endoscopy was performed preoperatively and 6 (20 patients) and 48 months (16 patients) postoperatively. RESULTS: There were positive correlations between Ki-67 and Bcl-2 levels in the EGJ (p > 0.001) and in the distal (p = 0.001) and proximal esophagus (p = 0.013). Compared to the preoperative level, Ki-67 expression was elevated in the distal (p = 0.012) and proximal (p = 0.007) esophagus at 48 months. In addition, compared to control values, Ki-67 expression was lower at the 6-month follow-up in the EGJ (p = 0.037) and the proximal esophagus (p = 0.003), and higher at the 48-month follow-up in the distal esophagus (p = 0.002). Compared to control values, Bcl-2 was lower at 6 months in the EGJ (p = 0.038). CONCLUSIONS: Proliferative activity after fundoplication increased in the long term in the distal esophagus despite a normal fundic wrap and healing of GERD.

The expression of 8-hydroxydeoxyguanosine in oesophageal tissues and tumours.

PURPOSE: The most common marker of oxidative DNA damage is 8-hydroxydeoxyguanosine (8-OHdG), which is linked with several malignancies. In the present study we investigated whether DNA damage linked to oxidative stress (as 8-OHdG) is present in Barrett's mucosa with or without associated adenocarcinoma or high-grade dysplasia and in normal controls' squamous mucosa. EXPERIMENTAL DESIGN: We measured 8-OHdG in 51 patients (13 Barrett's metaplasia, six Barrett's oesophagus with high-grade dysplasia, 18 adenocarcinoma of the distal oesophagus/oesophagogastric junction and 14 normal controls). The amount of DNA damage was determined by high-performance liquid chromatography in oesophagus samples obtained either from endoscopy or as samples from surgery. The median 8-OHdG concentration was expressed as the ratio of 8-OHdG per 10(5) deoxyguanosine. RESULTS: Analysis revealed that 8-OHdG was present in both Barrett's metaplasia with and without dysplasia as well as in adenocarcinoma of the oesophagus/oesophagogastric junction. Although the study group was small the amount of 8-OHdG was significantly increased in the distal oesophagus both in Barrett's epithelium 1.26 (0.08-29.47) and in high-grade dysplasia 1.35 (1.04-1.65) as well as in adenocarcinoma of oesophagus/oesophagogastric junction 1.08 (0.59-1.94) compared to controls 0.06 (0-4.08) (p=0.002, p=0.012, p=0.001, respectively). Barrett's patients had no significant difference in 8-OHdG levels between their distal and proximal oesophageal samples. CONCLUSIONS: Our results show the presence of oxidative DNA damage in the distal oesophagus of patients with Barrett's oesophagus and adenocarcinoma of the oesophagus/oesophagogastric junction. This may have a connection to carcinogenesis in Barrett's oesophagus.

Inoperable adenocarcinoma of the oesophagogastric junction: a comparative clinical study of laser coagulation versus self-expanding metallic stents with special reference to cost analysis.

AIMS: Neither clinical nor financial comparisons yet exist between self-expanding metallic stents (SEMS) and laser therapy, concentrating on the treatment of obstructive adenocarcinomas of the oesophagogastric junction. The aim of our study was to compare the relative lifetime costs and clinical results of the Nd:YAG laser to those of SEMS as alternative forms of primary palliation of dysphagia for adenocarcinoma near the oesophagogastric junction. METHODS: Fifty-two patients with distal oesophageal or oesophagogastric adenocarcinomas underwent palliative treatment for dysphagia: 32 treated with laser therapy and 20 with SEMS in this retrospective study. The clinical outcome and real cumulative costs as physical units and in financial terms were analysed for these study groups. RESULTS: Although patients palliated with SEMS underwent fewer procedures (1.9+/-1.6 vs 3.4+/-4.0, P=0.0048) and spent less time in endoscopic theatre (38+/-25min vs 118+/-152min, P=0.0048), they spent as many days in hospital (12.9 vs 15.1, P=0.370) and required as high overall costs for therapy (5360 EUR vs 5450 EUR, P=0.679) as those treated with laser therapy. In addition, they had higher morbidity rates (30 vs 6.3%, P=0.043), hospital mortality (20 vs 3.1%, P=0.066), and 30-day mortality (40 vs 3.1%, P=0.0011) than did patients with laser therapy, with no evidence of SEMS being the more effective treatment modality. CONCLUSIONS: In patients with adenocarcinoma at the distal oesophagus or at the oesophagogastric junction, laser therapy palliates dysphagia effectively with lower morbidity and mortality rates and without increased costs or hospital stays than does use of self-expanding metallic stents.

The epidemiology of oesophageal adenocarcinoma: has the cancer of gastric cardia an influence on the rising incidence of oesophageal adenocarcinoma?

BACKGROUND: Owing to overgrowth and definitional problems in classification, the cancer of gastric cardia may affect significantly the epidemiological analysis of oesophageal adenocarcinoma. The purpose of the present study was to evaluate the changes in the incidence of all the adenocarcinomas near the gastrooesophageal junction. METHODS: Trends in the incidence rates of adenocarcinoma of the oesophagus and the gastric cardia were described through the Finnish Cancer Registry. The annual age-standardized incidence rates during 1976-95 were analysed by a linear regression technique. RESULTS: The total incidence of oesophageal carcinoma remained around 3.5/100,000 in men, and decreased from 2.8 to 1.3/100,000 in women. The incidence of oesophageal adenocarcinoma increased from 0.28 to 0.77/100,000 (nearly 300%) in males, and from 0.08 to 0.11 per 100,000 in females. There were no significant changes with time in the incidence rate of gastric cardia cancer in either sex. Combined gastric cardia and oesophageal adenocarcinoma incidence rates remained stable in women, and increased slightly, but significantly, from 2.4 to 2.9/100,000 in men. CONCLUSION: Oesophageal adenocarcinoma has increased significantly in men in Finland, but the combined incidence of cancers of the gastro-oesophageal junction has increased only slightly. To overcome the difficulties in classification of oesophageal adenocarcinoma and the cancer of gastric cardia in the epidemiological studies, the focus should be on all adenocarcinomas at or near the oesophagogastric junction.

Subacute primary Candida lung abscess.

A case of primary subacute Candida lung abscess is described. The most reliable way to diagnose a rare pulmonary disease is to perform an open lung biopsy. A review of the literature suggests that the diagnosis of a primary subacute abscess due to Candida albicans in vivo is unique.