Nasal-type NK/T cell lymphoma is an increasingly recognised disease entity of aggressive clinical behaviour. The objective of this study was to investigate clinical features and treatment outcomes in patients with nasal-type NK/T cell lymphoma. From January 1991 to December 2003, 26 patients diagnosed as nasal-type NK/T cell lymphoma were included in the analysis. One half of patients presented with poor performance status (ECOG X2); 46% of patients were categorised as high intermediate or high-risk group according to IPI; and 46% of patients were diagnosed at advanced stage. The median survival for 26 patients with nasal-type NK/T cell lymphoma was 7.4 months (95% CI, 0.1, 16.9). The treatment outcome of primary anthracycline-based chemotherapy was poor: 60% CR rate in localised disease and 0% CR rate in advanced disease. After a median follow-up of 24.4 months (range 3.1 -99.0) in patients with localised disease who had achieved a CR (range 29.6 -165.7), three patients (50.0%) developed disease recurrence at 6.1, 21.8, and 52.1 months, respectively, and all patients presented with locoregional failure. The predictive factors for poor survival were of age greater than 60, advanced stage and poor performance in multivariate analysis. In conclusion, Nasal-type NK/T cell lymphomas showed a poor response to the conventional anthracycline-based chemotherapy, and thus an investigation for an innovative therapy is urgently needed to improve survival in these patients.

As a more effective in vivo drug delivery system, several methods loading anti-cancer drugs to biodegradable and biocompatible nano-particles have been explored and developed. Supposedly due to the enhanced permeability and retention (EPR) effect, systemic administration of these nano-particles have been found to result in accumulation of nano-particles into solid tumors. In this study, we prepared nano-particles using polyethylene glycol (PEG)/poly-L-lactide (PLLA) diblock copolymer and loaded doxorubicin into these nano-particles (Nano-dox). The fabricated nano-particles exhibited sustained release kinetics of the drug in vitro. To follow the in vivo biodistribution of 200-350 nm sized nano-dox particles in tumor (syngenic renal cell adenocarcinoma: RENCA) bearing mouse, the carboxylfluorescenin diacetate succinimidyl ester (CFSE) was loaded into the nano-particles. Nano-dox accumulated preferentially in tumors; however, in terms of its anti-tumor efficacy, it did not show any marked benefits, compared to freely-administered doxorubicin. This result suggests the need to re-consider and evaluate what type of anti-cancer reagents we to be used in the ongoing efforts of coupling drug delivery system with tumor EPR effects.

We read with interest the comments raised by Gong et al.1 on our recently published study, 2 and appreciate these important and critical remarks.We agree that contamination is a potential important problem with polymerase chain reaction (PCR)-based work. To avoid the possibility of contamination, we confirmed our data before completion of our manuscript. We performed the PCR experiment using new experimental reagents at a different laboratory. We also repeated the PCR to detect the fusion using two different set of primers, the new primer set producing longer amplicons than the old primer set. All these efforts produced identical results, confirming that our samples were not contaminated by PCR amplicons.As the direct fusion of one exon of CTLA4 to an exon of CD28 is less likely than fusion breakpoints within the introns, we confirmed direct fusion of the two exons at the genomic DNA level with other experiments before submitting our manuscript. As shown in Figure 1, direct fusion of exon 3 of CTLA4 to exon 4 of CD28 was confirmed by PCR using primers from intron 2 of CTLA4 and the 3' region of CD28 using genomic DNA from formalin-fixed, paraffin-embedded samples. PCR products were validated by Sanger sequencing. DNA from normal blood was used as a control as well as no template controls. These data confirm that the fusion is present at the DNA level and is not the result of contamination.We also tried to perform fluorescent in situ hybridization experiments. However it was difficult to design probes which can distinguish the fusion segment because the CD28 and CTLA4 genes are located very close to each other. As shown in our manuscript 2 in Online Supplementary Figure S5, the result was not helpful for delineating the fusion signal from the normal signal.