Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells.

Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof) on murine (CT26) and human (HT29) colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 10(9) CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells). In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 10(9) CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain.

Biomarkers of head and neck cancer, tools or a gordian knot?

Head and neck tumors comprise a wide spectrum of heterogeneous neoplasms for which biomarkers are needed to aid in earlier diagnosis, risk assessment and therapy response. Personalized medicine based on predictive markers linked to drug response, it is hoped, will lead to improvements in outcomes and avoidance of unnecessary treatment in carcinoma of the head and neck. Because of the heterogeneity of head and neck tumors, the integration of multiple selected markers in association with the histopathologic features is advocated for risk assessment. Validation of each biomarker in the context of clinical trials will be required before a specific marker can be incorporated into daily practice. Furthermore, we will give evidence that some proteins implicated in cell-cell interaction, such as CD44 may be involved in the multiple mechanism of the development and progression of laryngeal lesions and may help to predict the risk of transformation of the benign or precancerous lesions to cancer.

Pleomorphic hepatocellular carcinoma following consumption of hypericum perforatum in alcoholic cirrhosis.

Hepatocellular carcinoma (HCC) often develops in patients with underlying liver disease, yet HCC with syncytial giant cells (SGCs) is extremely rare. Herein, we report a 55-year-old man with a 6-year history of alcoholic cirrhosis who during his regular checkup presented with marked elevation of alpha-fetoprotein. Clinical examination and imaging analyses revealed a tumor-like lesion in segment 4 of the liver, which was removed by limited wedge resection. Histological analysis by hematoxylin and eosin staining indicated pleomorphic and atypical nodules, with some SGCs, embedded within the boundaries of the neoplastic lesion. The adjacent liver parenchyma showed microvesicular steatosis, pericellular fibrosis, and moderate hemosiderin accumulation (grade 2, as determined by Prussian blue iron stain) in hepatocytes and Kupffer cells but no copper accumulation (as determined by orcein stain). Immunohistochemical analysis showed hepatocyte antigen-positive staining for the neoplastic cells and SGCs. The diagnosis was made for cirrhosis-related HCC with SGCs. The previous reports of pleomorphic HCC have featured osteoclast-like (i.e., mesenchymal type) giant cells, making this case of epithelial type giant cells very rare. The patient's 6-month history of hypericum perforatum/St John's wort self-medication may have prompted the cirrhosis or HCC progression or the unusual SGC manifestation.

Short-term ventricular restraint attenuates post-infarction remodeling in rats.

BACKGROUND/OBJECTIVES: Left ventricular restraint attenuates post-infarction remodeling, but may be associated with unfavorable long-term histological response. We hypothesized that beneficial effects can be obtained with short-term restraint during the early post-infarction period; for this purpose, we evaluated a biodegradable scaffold in the in vivo rat model and compared it with epicardial hydrogel application. METHODS: A total of 230 Wistar rats (358 ± 7 g) were studied. Implantation was performed with and without prior myocardial infarction, induced by permanent coronary artery ligation. Diastolic filling was evaluated by left ventricular pressure recordings after scaffold implantation. Degradation rates and inflammatory/foreign body response were studied at 3, 7 and 15 days post-ligation. Remodeling indices were evaluated by echocardiography 15 days post-ligation. RESULTS: No differences were found in diastolic pressure. Biodegradability was ~50% by 7 days and 100% by 15 days for both materials. Likewise, inflammatory/foreign body response peaked at 3 days post-implant, with subsequent remission, but fibroblastic reaction was more pronounced after scaffold than after hydrogel implantation. Post-ligation, ejection fraction was higher in the scaffold (40.0 ± 1.5%) or hydrogel groups (37.0 ± 1.3%), compared to controls (30.6 ± 1.9%). Wall tension index was lower with either biomaterial, but left ventricular end-diastolic diameter was shorter (p=0.044) and sphericity was attenuated (p=0.029) after scaffold, compared to hydrogel implantation. CONCLUSIONS: Both biomaterials showed a favorable histological response and attenuated remodeling, but epicardial restraint produced better results compared to hydrogel alone. The latter approach merits further investigation due to the ease of implantation.