Barrett's oesophageal adenocarcinoma encompasses tumour‐initiating cells that do not express common cancer stem cell markers

Accumulating evidence has suggested that tumours have a hierarchical organization in which only the cancer stem cells (CSCs) have tumour‐initiating properties. Several surface antigens have been employed to isolate CSCs from various malignancies, although not from oesophageal adenocarcinoma (EA). We tested whether Barrett's oesophagus (BE) and EA might serve as a model for the CSC concept. In vivo assays were performed by transplantation of serially diluted bulk EA cells into NOD‐SCID mice to establish the presence and frequency of tumour‐initiating cells. These were found to be present as ca. 1 in 64 000 cells. The transplanted tumours fully recapitulated the primary lesions. Subsequently, a panel of previously established CSC markers was employed for immunohistochemistry. CD24, CD29 and CD44 showed heterogeneous staining in EA. Nuclear β‐catenin accumulation increased during progression from metaplasia to dysplasia and was often observed in the basal compartment with CD24 and CD29 staining. However, the overall staining patterns were not such to clearly point out specific candidate markers. Accordingly, all markers were employed to sort the corresponding subpopulations of cancer cells and transplant them at low multiplicities in NOD‐SCID mice. No increased tumour‐initiating capacity of sorted EA cells was observed upon transplantation. These results indicate that tumour‐initiating cells are present in EA, thus reflecting a hierarchical organization. However, antibodies directed against novel surface antigens are needed to detect subpopulations enriched for CSCs in EA by transplantation assays. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Chemopreventive efficacy of piperine in 7,12-dimethyl benz [a] anthracene (DMBA)-induced hamster buccal pouch carcinogenesis: An FT-IR study

The present study is designed to investigate the effect of piperine in modifying the carcinogenic process, as well as biochemical alterations at the molecular level during DMBA-induced hamster buccal pouch carcinogenesis by FT-IR spectroscopy. Specific changes were noticed in the FT-IR spectral features of DMBA-induced hamster buccal pouch carcinoma. These alterations include structural changes of proteins and possible increase of its content, an increase in the nuclear-to-cytoplasm ratio, an increase in the relative amount of DNA, an enhancement in the phosphorylation of proteins, a loss of hydrogen bonding of the C–OH groups in the amino acid residues of proteins and diminished lipid peroxidation which were accompanied by a significant reduction in the relative amount of lipids compared to untreated control animals. Administration of piperine significantly increased the levels of lipid peroxidation and decreased the levels of proteins and nucleic acid content that were found to increase in oral cancer bearing animals. In conclusion, the results of the present study suggest that piperine may exert its chemopreventive effect by modulating the biochemical changes at the molecular level during DMBA-induced hamster buccal pouch carcinogenesis which can be detected using FT-IR spectroscopic technique.     

Comparison of Diaton transpalpebral tonometer with applanation tonometry in keratoconus

AIM: To investigate the added value of using a Diaton transpalpebral tonometer (DT) to measure IOP in keratoconus. Most type of tonometers use corneal applanation or biomechanical resistance to measure intraocular pressure (IOP); however, these factors can be altered by keratoconus. Specifically, we examined whether DT can detect false-negative low Goldmann applanation tonometry (AT) measurements. METHODS: Patients with keratoconus were recruited from our tertiary academic treatment center. Measurements included AT and DT (in random order) and Scheimpflug imaging. An age- and gender-matched group of control subjects with no history of corneal disease or glaucoma was also recruited. RESULTS: In total, 130 eyes from 66 participants were assessed. In the keratoconus group, mean AT was 11.0 ± 2.6, mean DT 11.2±5.5 (P=0.729), and the two measures were correlated significantly (P=0.006, R=0.323). However, a Bland-Altman plot revealed a wide distribution and poor agreement between both measurements. Previous corneal crosslinking, corneal pachymetry, and Krumeich classification had no effect on measured IOP. CONCLUSION: Measurements obtained using a Diaton tonometer are not affected by corneal biomechanics; however, its poor agreement with Goldmann AT values calls into question the added value of using a Diaton tonometer to measure IOP in keratoconus.