No abstract

The trace element selenium is discussed as a chemopreventive agent in colorectal carcinogenesis. Selenocysteine-containing proteins, so-called selenoproteins, represent potential molecular targets for nutritive selenium supplementation. Due to their antioxidative potential, the selenoproteins gastrointestinal glutathione peroxidase (GI-GPx) and selenoprotein P (SePP) are considered to provide protection against reactive oxygen species (ROS), thereby reducing DNA damage and preventing development of colon cancer. GI-GPx and SePP are abundantly expressed in normal colon mucosa. Recently, we demonstrated both reduced SePP expression and increased GI-GPx expression in colorectal adenomas. In this study, we investigated the expression of SePP and GI-GPx in colorectal cancers compared with corresponding normal mucosa. Further, the occurrence of genetic alterations within the SePP and GI-GPx genes was analyzed. We observed a significant reduction or loss of SePP mRNA expression in colon cancers, whereas GI-GPx mRNA and protein expression varied between different tumor samples. In addition, we identified novel polymorphisms within the SePP and GI-GPx genes with so far unknown relevance for protein function. Our results argue against a general decrease of selenoprotein expression in colorectal carcinogenesis but imply specific differential regulation of expression of individual selenoproteins.

Only limited data are available on selective serotonin re-uptake inhibitor (SSRI) prophylaxis for antiviral re-treatment in hepatitis C patients with previous interferon-induced major depressive episodes. Therefore, we investigated the efficacy and safety of secondary SSRI prophylaxis in these patients. In a prospective and longitudinal study, repeated psychometric testing (Hospital Anxiety and Depression Scale) was performed before, during, and after antiviral re-treatment. Chronic hepatitis C virus (HCV)-infected patients, who had been psychometrically monitored during an unsuccessful previous antiviral therapy, and had developed major depression were included. Interferon re-therapy with SSRI prophylaxis was started (n = 8). The reference group was comprised of HCV patients without a history of interferon-associated depression and also a group who were previously unsuccessfully treated with interferon and were re-treated without SSRI prophylaxis (n = 9). All patients receiving SSRI prophylaxis were able to complete interferon re-therapy as scheduled. As in the first therapeutic course, depression scores were significantly elevated during re-treatment also (P < 0.001). Depression scores were significantly lower (P =0.036) during interferon re-therapy with SSRI prophylaxis. Reference group subjects showed similar depression scores during first therapy and re-therapy (P > 0.05). In conclusion, hepatitis C patients with a history of interferon-induced major depression can be successfully re-treated with peginterferon/ribavirin and concomitant SSRI prophylaxis. In these patients, SSRI prophylaxis is safe and efficacious and should be considered, if antiviral re-therapy is indicated.

Reactivation of chronic hepatitis B in patients receiving cytotoxic treatment for non-Hodgkin's lymphoma is well documented. We report a case of a patient with chronic hepatitis B who was treated by chemotherapy because of non-Hodgkin's lymphoma. After the second cycle of chemotherapy she developed a severe flare-up of hepatitis B. Liver biopsy revealed highly active hepatitis and confluent necroses. Within 3 weeks, the patient recovered spontaneously. Prophylactic treatment with lamivudine (Epivir,Glaxo-Wellcome, 150 mg b.i.d.) led to a decrease of HBV-DNA below the detection limit. Further chemotherapy was administered and autologous stem cell transplantation was successfully performed without another reactivation of hepatitis B. Antiviral treatment was stopped 16 weeks after stem cell retransfusion. So far, no further flare-up of hepatitis B has occurred and the patient's lymphoma has not relapsed. Thus, the case described here indicates a possible role of lamivudine in preventing hepatitis B flare-up during antineoplastic chemotherapy. We suggest that lamivudine be considered for prophylaxis against fulminant hepatitis in patients with chronic HBV infection undergoing high-dose antineoplastic therapy.

Our results suggest that in addition to classical LOH, cnLOH is an important mutational event in relation to the carcinogenesis of MSS and MSI tumors, causing the inactivation of a tumor suppressor gene without copy number alteration of the respective region; this is crucial for the development of MSI tumors and for some chromosomal regions in MSS tumors.