180. The role of surgery in management of limited disease (LD) small cell lung cancer (SCLC), a retrospective comparative study

To asses the role of surgery in SCLC we performed a retrospective analysis of survival in two groups of LD patients (pts) treated between 1982 and 1995. In one group (67 pts) complete resection was followed by chemotherapy, the other (67 pts) was treated with conventional nonsurgical management. In all operated pts the diagnosis of SCLC was established only after the examination of surgical specimen. The non-surgical group was selected using “pair-matched case-control” methodology out of 176 LD pts potentially suitable for surgery (i. e. no pleural effusion or other local advancement, no supraclavicular lymph node involvement, good PS) but treated with non-surgical approach. Total series included 109 males and 25 females, 20 T1 and 114 T2 disease, 51 N0, 43 N1 and 40 N2 disease. In the surgical group 23 pts received prophylactic cranial irradiation and in the non-surgical group 39 pts received thoracic irradiation. The most important prognostic factors were well balanced between both groups. Median survival in pts treated with and without surgery was 22 months and 11 months, respectively (p<0.001). The two-year and five-year survival rates were 43% and 27% in the surgical group, and 17% and 4% in the non-surgical group. Significantly longer survival in pts treated with surgery was found in all T and N categories except N2 disease. Local relapse was more frequent in pts treated with conventional management (55%) then in surgical group (15%, p<0.001). Distant relapse rates were similar in both groups (36% and 40%, respectively). The most common site of metastases in the entire series was CNS followed by liver, lymph nodes, bones, lungs and skin. We conclude, that surgery may have a positive impact on survival of LD SCLC pts, thus a randomized study is warranted to address this issue

Does chemotherapy-induced leukopenia predict a response in small cell lung cancer?

The correlation between chemotherapy-induced toxicity and treatment outcome in cancer patients has not been studied thoroughly. Our aim was to evaluate whether there is any relationship between chemotherapy-induced leukopenia and response to treatment in small-cell lung cancer (SCLC). Data derived from records of 228 patients treated within two prospective multicentre phase II studies were analysed. In the first study (101 patients) chemotherapy included vincristine, epirubicin and cyclophosphamide and, in the second (127 patients), cyclophosphamide, etoposide and epirubicin; both regimens were given every 3 weeks. In the present analysis, the correlation between treatment outcome (response rate and survival) and highest scores of leukopenia within the first two and up to the fourth chemotherapy cycle, respectively, was evaluated. The objective response rate for the entire group was 66%; 53% in patients whose white blood cells remained normal and 85% in those who developed leukopenia within the first two cycles (P = 0.000). In multifactorial analysis, also including other treatment- and patient-related factors, independent correlation with response to chemotherapy was found for leukopenia (P = 0.001), chemotherapy regimen (P = 0.002) and the combined relative dose intensity (P = 0.018), but not for patient sex, age, performance status, pre-study weight loss, extent of disease and initial white blood cell count. Leukopenia within the first two cycles of chemotherapy was not correlated with survival, whereas such correlation for leukopenia occurring up to the fourth cycle was at the borderline level (P = 0.06). These findings suggest a relationship between chemotherapy-induced leukopenia and tumour response in SCLC

Autopsy findings in small cell lung cancer

The objective of this study was to assess the pattern of autopsy findings in 174 small cell lung cancer patients treated between 1971 and 1991 at seven Polish medical centres. Eighty-nine autopsied patients were previously treated with different chemotherapy regimens including 32 patients who also received chest irradiation, 74 received only supportive care and for 11 patients the data on treatment were not available. The age range at diagnosis was 28-81 years (median 57); there were 39 females (22%) and 135 males (78%). Seventy-two patients had limited disease at the time of diagnosis, 86 - extensive disease and in 16 the disease extent was not determined. The primary tumor and/or metastases in regional lymph nodes were present in 157 autopsies (90%). There was a significant difference in the rate of locoregional disease found at autopsy in patients given chemotherapy and in those who received only supportive care (85% and 100%, respectively; p = 0.01). Chest radiation therapy given in limited disease as an adjunct to chemotherapy did not decrease the rate of persistent locoregional disease (primary tumor in the chest was found in 92% of irradiated and in 96% of nonirradiated patients). Locoregional tumor deposit only was found in 28 (16%). Distant metastases were distributed in 143 patients (82%) and were found in 25 different locations, most frequently in liver (49%), suprarenal glands (25%), peripheral lymph nodes (21%), kidneys (18%), brain (17%) and pancreas (12%). In 3 patients no tumor foci were found. The number of organs involved varied between 0 and 10 (median 3). The number of involved organs was not dependent on the disease extent at the time of diagnosis and on the type of treatment

Membrane-Less Biofuel Cell Based on Cellobiose Dehydrogenase (Anode)/Laccase (Cathode) Wired via Specific Os-Redox Polymers

A membrane-free biofuel cell (BFC) is reported based on enzymes wired to graphite electrodes by means of Os-complex modified redox polymers. For the anode cellobiose dehydrogenase (CDH) is used as a biocatalyst whereas for the cathode a laccase was applied. This laccase is a high-potential laccase and hence able to reduce O-2 to H2O at a formal potential higher than +500 mV versus Ag/AgCl. In order to establish efficient electrochemical contact between the enzymes and graphite electrodes electrodeposition polymers containing Os-complex with specifically designed monomer compositions and formal potentials of the coordinatively bound Os-complex were synthesised and used to wire the enzymes to the electrodes. The newly designed CDH/Os-redox polymer anode was characterised at different pH values and optimised with respect to the nature of the polymer and the enzyme-to-polymer ratio. The resulting BFC was evaluated running on beta-lactose as a fuel and air/O-2 as an oxidising agent. The power output, the maximum current density and the electromotor force (E-emf) were found to be affected by the pH value, resulting in a maximum power output of 1.9 mu W cm(-2) reached at pH 4.3, a maximum current density of about 13 mu A cm(-2) at pH 3.5, and the highest E-emf approaching 600 mV at pH 4.0

White Spot Syndrome Virus IE1 and WSV056 Modulate the G(1)/S Transition by Binding to the Host Retinoblastoma Protein

National Basic Research Program of China (973 Program) [2012CB114401]; National Natural Science Foundation of China [40976100]; China Agriculture Research System [CARS-47]DNA viruses often target cellular proteins to modulate host cell cycles and facilitate viral genome replication. However, whether proliferation of white spot syndrome virus (WSSV) requires regulation of the host cell cycle remains unclear. In the present study, we show that two WSSV paralogs, IE1 and WSV056, can interact with Litopenaeus vannamei retinoblastoma (Rb)-like protein (lv-RBL) through the conserved LxCxE motif. Further investigation revealed that IE1 and WSV056 could also bind to Drosophila retinoblastoma family protein 1 (RBF1) in a manner similar to how they bind to lv-RBL. Using the Drosophila RBF-E2F pathway as a model system, we demonstrated that both IE1 and WSV056 could sequester RBF1 from Drosophila E2F transcription factor 1 (E2F1) and subsequently activate E2F1 to stimulate the G(1)/S transition. Our findings provide the first evidence that WSSV may regulate cell cycle progression by targeting the Rb-E2F pathway