Laryngeal Transplantation in 2005: A Review

There is no good surgical, medical or prosthetic solution to the problems faced by those with a larynx whose function is irreversibly damaged by tumor or trauma. Over the past 10 years, the pace of research designed to establish laryngeal transplantation as a therapeutic option for these persons has increased steadily. The biggest milestone in this field was the world's first true laryngeal transplant performed in Cleveland, Ohio in 1998. The recipient's graft continues to function well, in many respects, even after 7 years. However, it has also highlighted the remaining barriers to full-scale clinical trials. Stimulated by these observations, several groups have accumulated data which point to answers to some of the outstanding questions surrounding functional reinnervation and immunomodulation. This review seeks to outline the progress achieved in this field by 2005 and to point the way forward for laryngeal transplantation research in the 21st century.     

Characterization of cell death events induced by anti-neoplastic drugs cisplatin, paclitaxel and 5-fluorouracil on human hepatoma cell lines: Possible mechanisms of cell resistance.

Two different hepatoma cell lines were incubated for 48h with chemotherapeutic drugs cisplatin, paclitaxel and 5-FU to determine their ability to induce cytotoxicity and DNA fragmentation as well as to modify the expression of some cell death-related genes that could be involved in the resistance to therapy. We observed that cisplatin and paclitaxel induced cytotoxicity, but significant differences between both cell lines, were found only in the case of paclitaxel. At 48h, apoptosis was clearly present in Hep3B cells treated with cisplatin and HepG2 cells treated with paclitaxel. 5-FU induced cytotoxicity in both cell lines but only at higher concentrations than the other two drugs, triggering apoptosis and necrosis in HepG2 cells and only necrosis in Hep3B. When a time course was performed for the first 8h of treatment to elucidate the initial mechanism of cell death responsible for DNA fragmentation, we observed that 5-FU in Hep3B, and cisplatin in both cell lines, induces primary necrosis, whereas at the concentration tested here, paclitaxel clearly triggers apoptosis in both cell lines. HepG2 cells were weakly sensitive to 5-FU in the first 8h of treatment, so the primary mechanism of cell death was not clear, but results seem to indicate that it could be apoptosis. At 48h, Bax was not up-regulated with any of the treatments, whereas cisplatin was able to induce Bcl-xL down-regulation in both cell lines. Treatment with 5-FU also down-regulated Bcl-xL in HepG2 cells. We also measured variations in the expression of survivin, an inhibitor of apoptosis that has also been involved in mitototic catastrophe. Hep3B cells seem to show an increase in protein levels with all treatments. Exposure to paclitaxel resulted in the highest effect. In the case of HepG2 cells, there was a decrease in survivin expression when cells were treated with 5FU and paclitaxel, both treatments showing complete loss of the protein. Using an antibody that recognizes unprocessed caspase-3, we observed that the enzyme was assumingly activated in HepG2 cells treated with 5FU and paclitaxel, but only weakly after treatment with cisplatin. Hep3B cells did not show activation since the levels of the pro-enzyme remained the same as that in the control. In conclusion, the three drugs tested in this study could induce cell death, with paclitaxel being more effective inducing apoptosis. 5FU was only effective at high doses and its mechanism seems to be primarily related to necrosis in Hep3B and probably apoptosis in HepG2. Cisplatin mechanism of cell death is probably mediated by the decrease in anti-apoptotic protein Bcl-xL whereas paclitaxel and 5FU are decreasing the apoptosis inhibitor survivin. According to pro-enzyme levels, caspase-3 was only activated in HepG2 cells, whereas in the case of Hep3B cells the mechanisms of toxicity appear to be caspase-3-independent at the time and concentrations tested in this study. The resistance of Hep3B cells to death induced by chemotherapy could be related to an increase in the expression of IAP survivin, which can decrease cell response to the treatment or even switch the type of death from apoptosis to another kind, making therapy less efficient.     

Choices in oncology: factors that influence patients' treatment preference

Medical treatment of cancer often entails a trade-off between outcomes of two different attributes: quality of life (QOL) and length of life (LL). This process of weighing advantages and disadvantages seems to be influenced by different factors. The main purposes of this study were (a) to investigate the relative importance of different factors on the trade-off and (b) to explore the relationship between these importance ratings and personal characteristics. We asked 199 patients with cancer to indicate to what degree they consider a number of factors to be of importance if they had to choose between two treatment modallties that differ in their expected outcomes concerning QOL and LL. The seven factors were their age at the time of decision, having a partner, having children, inability to work due to side-effects of the treatment, the nature of the side-effects, disease-related life expectancy and baseline QOL. The results indicate that six of the seven factors were of considerable to great importance when a treatment choice had to be made. The negative effects of treatment on the ability to work did not seem to be a very important consideration. Patient age and education were positively associated with importance ratings.Supported by the Dutch Cancer Society (Project IKW 90-13).     

A rare case of nasopharyngeal angiofibroma in an elderly female

Nasopharyngeal angiofibromas occur predominantly in males in their puberty and adolescence; the incidence in other age groups and in women is exceptional. This report describes a case of a 57-year-old woman with nasopharyngeal angiofibroma presenting typical radiological findings in computed tomography, MR imaging and angiography. The tumour was successfully removed and histopathological examination confirmed the diagnosis. In 6 years follow-up the patient is free of symptoms.     

Ultraviolet Laser-Induced Fluorescence Spectroscopy Diagnosis of Human Stomach Malignant Tissues

To evaluate the potential of laser-induced autofluorescence spectroscopy for the detection of premalignant lesions of human stomach, fluorescence properties of stomach tissues have been investigated in vitro and in vivo. A specially made optical fibre probe and the multichannel fluorescence collection system have been used successfully in our research. Paper received 26 June 1997; accepted in revised form 31 October 1997.     

Experimental models of colorectal cancer

PURPOSE: A review ofin vivo andin vitro models of colorectal cancer is presented. METHODS: A retrospective literature review was performed with reference to CD-ROM Medline and Index Medicus. RESULTS: A comparison of the advantages and disadvantages of the models is presented in addition to a summary of individual model methodology and applications. CONCLUSIONS: Such models are a useful adjunct for surgical research in colorectal oncology.Mr. Banerjee is in receipt of support from the Yorkshire Cancer Research Organization.