ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the value of normalization window of tumor vasculature (NWTV) in patients with unresectable gastric cancer undergoing neoadjuvant chemotherapy.</p><p><b>METHODS</b>From October 2010 to March 2011, 93 patients with unresectable advanced or locally advanced gastric carcinoma were prospectively collected and randomly divided to Group A(n=30), Group B(n=29), and Group C(n=34). Group A received FOLFOX4 as conventional neoadjuvant chemotherapy. Group B received FOLFOX4 plus bevacizumab. The treatment was adjusted in Group C according to the hypothesis of NWTV with neoadjuvant chemotherapy delivered 5 days after bevacizumab treatment. The efficacy, drug toxicity and clinical outcome were assessed and compared between the three groups.</p><p><b>RESULTS</b>There were no significant differences among the 3 groups in demographics(P>0.05). All the patients completed the neoadjuvant chemotherapy. Efficacy and toxicity between the three groups were comparable(P>0.05). The rates of tumor downstaging in the three groups were 56.7%(17/30), 72.4%(21/29), 85.3%(29/34), respectively, with a significantly lower downstaging rate in Group C as compared to Group A(P<0.05). R0 resection rates were 23.3%(7/30), 27.6%(8/29), 52.9% (18/34), respectively, with significantly higher R0 resection rate in Group C as compared to Group A and Group B(All P<0.05). There was no perioperative death in this cohort. Postoperative complications were comparable among the 3 groups(P>0.05).</p><p><b>CONCLUSIONS</b>Anti-angiogenesis agent can improve the efficacy of neoadjuvant chemotherapy in unresectable gastric cancer. Furthermore, administration according to NWTV may achieve better outcomes.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Antibodies, Monoclonal, Humanized , Therapeutic Uses , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Bevacizumab , Fluorouracil , Therapeutic Uses , Leucovorin , Therapeutic Uses , Neoadjuvant Therapy , Neovascularization, Pathologic , Drug Therapy , Organoplatinum Compounds , Therapeutic Uses , Prospective Studies , Stomach Neoplasms , Drug Therapy , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To evaluate the antitumor efficacy of Ad-TD-RFP for human nasopharyngeal carcinoma cells (C666-1) in vitro and in vivo.</p><p><b>METHODS</b>The oncolytic effects of Ad-TD-RFP and control virus dl11520 on C666-1 cells were determined by cytotoxicity assay (MTS assay). Viral replication of Ad-TD-RFP and dl11520 was detected at different time points (24 h, 48 h, 72 h and 96 h) by tissue culture infective dose (TCID(50)) in C666-1 cells implanted subcutaneously into the flank in each of BALB/c nude mice. The xenografts were injected intratumorally with Ad-TD-RFP or dl1520 to investigate their effects on tumor growth.</p><p><b>RESULTS</b>The concentration for 50% of maximal effect (EC(50)) values of Ad-TD-RFP and dl1520 were (107.6 ± 3.2) pt/cell and (174.1 ± 4.0) pt/cell, respectively (t = 22.6, P < 0.001). The Ad-TD-RFP replication was 3-14 folds more than dl1520 replication at four time points (24 h, 48 h, 72 h and 96 h) in C666-1 cells (t values were 33.6, 23.4, 20.8 and 17.3, respectively, P < 0.001). The average tumor volumes of PBS group, dl1520 group and Ad-TD-RFP group were (1765.5 ± 713.9) mm(3), (1036.9 ± 623.8) mm(3), and (420.8 ± 238.7) mm(3), respectively (F = 12.0, P < 0.05) on day 67 after treatment.</p><p><b>CONCLUSIONS</b>The antitumour efficacy of the novel oncolytic adenovirus Ad-TD-RFP for human nasopharyngeal carcinoma C666-1 cells is superior to that of dl1520 in vitro and in vivo. The outcome of this study provides an experimental basis for the treatment of human nasopharyngeal carcinoma by viral gene therapy.</p>