ABSTRACT
Next-generation sequencing has allowed identification of millions of somatic mutations in human cancer cells. A key challenge in interpreting cancer genomes is to distinguish drivers of cancer development among available genetic mutations. To address this issue, we present the first web-based application, consensus cancer driver gene caller (C), to identify the consensus driver genes using six different complementary strategies, i.e., frequency-based, machine learning-based, functional bias-based, clustering-based, statistics model-based, and network-based strategies. This application allows users to specify customized operations when calling driver genes, and provides solid statistical evaluations and interpretable visualizations on the integration results. C is implemented in Python and is freely available for public use at http://drivergene.rwebox.com/c3.
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the efficacy of short-term intermittent prophylactic use of a recombinant human thrombopoietin (rhTPO) in chemotherapy-induced severe thrombocytopenia in lung cancer patients.</p><p><b>METHODS</b>24 advanced non-small cell lung cancer (NSCLC) patients who experienced severe thrombocytopenia in the last chemotherapy cycle received prophylactic rhTPO treatment in the next chemotherapy cycle (prophylactic treated cycle, PTC). rhTPO was given subcutaneously 300 U×kg(-1)×d(-1) on days 2, 4, 6, and 9 after the initiation of chemotherapy. Platelet count was monitored and compared with that in the previous treatment cycle (control cycle, CC).</p><p><b>RESULTS</b>The lowest platelet count in the prophylactic rhTPO cycle was significantly higher than that in control cycle [(56 ± 16) × 10(9)/L vs. (28 ± 13) × 10(9)/L, P < 0.001]. The duration of thrombocytopenia was also shortened by the prophylactic rhTPO [(8 ± 2) d vs. (12 ± 3) d, P < 0.001]. The area under curve (AUC) of platelet count (21 days) was significantly increased [(3517 ± 685) × 10(9)/L vs. (2063 ± 436) × 10(9)/L, P < 0.001]. The time to platelet nadir and peak was not affected.</p><p><b>CONCLUSION</b>Prophylactic use of rhTPO can attenuate the severity and shorten the duration of chemotherapy-induced thrombocytopenia in lung cancer patients.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Adenocarcinoma , Blood , Drug Therapy , Pathology , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Area Under Curve , Carboplatin , Cisplatin , Deoxycytidine , Dizziness , Fever , Lung Neoplasms , Blood , Drug Therapy , Pathology , Neoplasm Staging , Platelet Count , Recombinant Proteins , Therapeutic Uses , Thrombocytopenia , Blood , Drug Therapy , Thrombopoietin , Therapeutic UsesABSTRACT
<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) in treatment for chemotherapy-induced thrombocytopenia in patients with lung cancer.</p><p><b>METHODS</b>Fifty-one lung cancer patients with platelet count < 100 x 10(9)/L after chemotherapy were enrolled into this study. They were divided into three groups: mild, moderate and severe thrombocytopenia groups according to the platelet count. rhTPO was subcutaneously administered at a dosage of 300 microg kg(-1) d(-1) until the platelet count >or= 100 x 10(9)/L or absolute value of platelet count >or= 50 x 10(9)/L. Laboratory tests included routine blood count, serum biochemistry, and blood coagulation test.</p><p><b>RESULTS</b>The duration of the chemotherapy-induced thrombocytopenia was significantly shorter in the mild group than that in the moderate and severe groups (P < 0.01). After administration of rhTPO, the time of declined platelet count beginning to recover was also significantly shorter in the mild group than that in the moderate and severe groups (P < 0.01). There was a statistically significant difference in platelet transfusion needed among the three groups (P < 0.01). However, no significant difference was found among the three groups in the time of rhTPO treatment (P > 0.05) and platelet count improvement (P > 0.05).</p><p><b>CONCLUSION</b>Recombinant human thrombopoietin can be effectively and safely administered to deal with grade III/IV chemotherapy-induced thrombocytopenia in lung cancer patients with mild adverse effects.</p>