The Impact of Bevacizumab (Avastin) on Survival in Metastatic Solid Tumors - A Meta-Analysis and Systematic Review

<div><h3>Purpose</h3><p>To evaluate the effect of Bevacizumab in combination with chemotherapy on overall survival of patients with metastatic solid tumors.</p> <h3>Design</h3><p>A systematic literature search to identify randomized trials comparing chemotherapy with and without Bevacizumab in metastatic cancer. The primary end point was overall survival (OS) and the secondary end points were progression free survival (PFS) and toxicity. A meta-analysis was performed for each tumor type and for the combination of all tumors.</p> <h3>Results</h3><p>24 randomized trials with 8 different types of malignancies were included in this meta-analysis. Patients treated with Bevacizumab had an OS benefit, hazard ratio (HR) 0.89 (95% CI 0.84–0.93, P<0.00001 I²-4%). The combined analysis showed a PFS benefit with a HR 0.71 (95% CI 0.68–0.74, P<0.00001, I²-54%). The toxicity analysis showed a statistically significant increase in fatal adverse events (FAEs) in the Bevacizumab treatment arm, risk ratio (RR) 1.47 (95% CI 1.1–1.98). A separate analysis of the lung cancer trials showed an increased risk of fatal pulmonary hemorrhage with a RR of 5.65 (95% CI 1.26–25.26). The risk of G3–4 adverse events was increased: RR 1.2 (95% CI 1.15–1.24).</p> <h3>Conclusion</h3><p>in this combined analysis Bevacizumab improved OS (with little heterogeneity) and PFS. These results should be considered in the light of lack of markers predictive of response and the increased severe and fatal toxicity seen with Bevacizumab treatment.</p> </div

An insight into the assembly and organization of Photosystem <span style="mso-bidi-font-weight:bold">I complex in thylakoid membranes of the thermophilic cyanobacterium, <i style="mso-bidi-font-style:normal">Mastigocladus laminosus</i> </span>

405-417The present study characterizes the assembly and organization of Photosystem I (PSI) complex, and its individual subuni ts into the thylakoid membranes of the thermophilic cyanobacterium, Mastigocladus laminosus. PSI is a multiprotein complex that contains peripheral as well as integral subunits. Hence. it serves as a suitable model system for understanding the formation and organization of membrane protein complexes. In the present study, two peripheral cytosol facing subunits of PSI. namely, PsaD and PsaE were overexpressed in E. coli and used for assembly studies. The gene encoding PsaK, an integral membrane spanning subunit of PSI, was cloned and the deduced amino acid sequence revealed PsaK to have two transmembrane α-helices. The characterization of the in vitro assembly of the peripheral subunits. PsaD and PsaE, as well as or the integral subunit, PsaK, was performed by incubating each subunit with thylakoids isolated from Mostigocladus laminosus. All three subunits studied were found to assemble into the thylakoids in a spontaneous mechanism, showing no requirement for eytosolic factors or NTP's (nucleotide 5'-triphosphate). Nevertheless. further characterization of the assembly of PsaK revealed its membrane integration to be most efficient at 55°C.   The associations and protein-protein interactions between different subunits within the assembled PSI complex were directly quantified by measurements performed using the BIACORE technology. The preliminary results indicated the existence of specific interaction between PsaD and PsaE. and revealed a very high binding affinity between PsaD and the PSI electron acceptor ferridoxin (Kd = 5.8 10-11 M). PsaE has exhibited a much lower binding affinity for ferridoxin (Kd = 3.1 10-11 M). thereby supporting the possibility of PsaE being one of the subunits responsible for the dissociation of ferridoxin from the PSI complex. </span

Trials protocols & data summary.

<p>Trials protocols & data summary.</p

Progression free survival.

<p>Progression free survival.</p

Toxicity analysis.

<p>Toxicity analysis.</p

Trial selection.

<p>Trial selection.</p

Progression free survival and overall survival in 2nd line metastatic breast cancer.

<p>Progression free survival and overall survival in 2nd line metastatic breast cancer.</p