Prostatakarzinom: Familiäres Risiko überschätzt?

Eine positive Familienanamnese gilt als starker Risikofaktor für ein Prostatakarzinom, da bei direkten Anverwandten der Patienten überproportional häufig ebenfalls ein Prostatakarzinom festgestellt wird. Doch der vermeintliche Zusammenhang täuscht und ist wohl zumindest teilweise durch einen Bias bei den epidemiologischen Erhebungen bedingt. Das legt eine Untersuchung von Ola Bratt et al. aus Helsingborg (J Natl Cancer Inst 2010; 102: 1–8) nahe.

Does severity of underlying chronic liver disease (CLD) affect treatment outcome of hepatocellular carcinoma (HCC) patients undergoing systemic chemotherapy (CT)?

e15513 Background: HCC is a common cause of morbidity and mortality. CT has been one of the treatments offered to patients (pts) who are not candidate of curative surgery. Treatment of HCC could be complicated by underlying CLD. In this study, we aimed to assess pre-CT severity of CLD on treatment outcome of HCC pts who were entered into our previously reported phase III prospective randomized CT study (J Natl Cancer Inst 2005). Methods: The severity of CLD for each pt was arbitrary assessed by adopting the Child-Pugh's classification. Patients’ characteristics were compared. Treatment outcomes in terms of responses, survival and treatment-related toxicities (NCI CTC) were compared. Results: 160 were Child's A; 28 were Child's B. Proportion of pts with cirrhosis (45% vs 71%, P=0.01) and pre-CT bilirubin level (11 vs. 15 umol/l, p=0.02) were significantly higher, while age (52 vs 45 yrs, p=0.05) and albumin level (35 vs 30 g/l, p<0.0001) were significantly lower among Child's B pts. For Child's A and B pts: the median no. of CT cycles received were 4.0 vs 2.5 (p=0.01), the response rates were 17% vs 8.3% (p=0.28), the median survival were 21 vs 10.7 months (p= 0.002). When toxicity during CT were compared, Child's B pts had significantly higher rate of grade 3/4 neutropenia (0.6% vs. 7.1%, p=0.05), hyperbilirubinaemia (11.9% vs. 28.6%, p=0.02), hyponatremia (3.1% vs. 3.6%, p=0.001) and gastrointestinal bleeding (3.1% vs. 17.9%, p=0.001). Conclusions: Child's B HCC pts experienced increased treatment-related toxicities during CT. This has probably led to a shorter duration of CT and a lower response rate to CT. Their shorter survival could also be attributed to the severity of underlying CLD. Future trials on systemic therapy in HCC patients may need to consider stratifying patients according to severity of CLD. No significant financial relationships to disclose.

Glutathione S-transferases of mouse lung. Selective binding of benzo[a]pyrene metabolites by the subunits which are preferentially induced by t-butylated hydroxyanisole

Six isoenzymes of glutathione S-transferase (GST) present in mouse lung have been purified and characterized. GST I (pI 9.8) is a dimer of Mr-26,500 subunits and GST II is a heterodimer of Mr-26,500 and -22,000 subunits, and GST III (pI 7.9) and IV (pI 6.4) are dimers of Mr-24,500 subunits. GST V (pI 5.7) is a heterodimer of Mr-24,500 and -23,000 subunits, whereas GST VI (pI 4.9) is a dimer of Mr-23,000 subunits. Immunological studies indicate that the Mr-24,500 subunits present in GST III (pI 7.9) are distinct from those present in GST IV (pI 6.4) and V (pI 5.7). Structural and immunological studies provide evidence that at least five distinct types of subunits in their different binary combinations give rise to various GST isoenzymes of mouse lung. These isoenzymes express varying degrees of catalytic activities towards a wide range of electrophilic substrates including benzo[a]pyrene 7,8-oxide and benzo[a]pyrene 4,5-oxide. The dietary antioxidant t-butylated hydroxyanisole (BHA) preferentially induces GST II and III. Also, these two isoenzymes selectively bind benzo[a]pyrene (B[a]P) metabolites, indicating that they play an important physiological role in the detoxification of B[a]P metabolites. The preferential induction of the GST isoenzymes involved in the detoxification of activated B[a]P metabolites indicates that the anti-neoplastic activity of BHA against B[a]P-induced neoplasia in mouse lung [Wattenberg (1973) J. Natl. Cancer Inst. 50, 1541-1544] may be due to the enhanced detoxification of B[a]P metabolites.

Short-term, high-efficiency expression of transfected DNA

We have achieved high-efficiency uptake and expression of foreign DNA in mouse Ltk- cells by modifying the DEAE-dextran-mediated transfection method of McCutchan and Pagano (J. Natl. Cancer Inst. 42:351-357, 1968) to include an initial incubation at elevated pH followed by a shock treatment with dimethyl sulfoxide. Up to 80% of mouse Ltk- cells transfected with the herpes simplex virus thymidine kinase gene expressed thymidine kinase as measured by autoradiography.