Time To Progress Research Articles

Relationship between Expression of beta-tubulin-III Plus Stathmin in Advanced Non-Small Cell Lung Cancer and its Sensitivity to Venorelbine Chemotherapy.

Vinorelbine plus cisplatin/carboplatin (NP) is one of the standard combination chemotherapy regimen for advanced non-small cell lung cancer (NSCLC). The aim of this study is to investigate the relationship between expression of Stathmin and beta-tubulin-III in NSCLC biopsies and sensitivity to Vinorelbine, which would provide a basis of the proper medicine choice for the patients' tailored chemotherapy. Western blot was used to investigate the expression of Stathmin and beta-tubulin-III protein in the biopsies from stage IIIB-IV NSCLC patients. All the cases were divided into 4 groups according to the level of the two proteins, of which L represented both protein expressed lowly, B showed beta-tubulin-III lowly expressed group, while S showed Stathmin lowly, and H represented both protein highly expressed. At the same time, all the patients accepted NP chemotherapy for 2 or 4 cycles according to the responses to this regimen. The responses rate (RR), media survival time (MST), time to progress (TTP) were observed. A total of 90 stage IIIB-IV NSCLC patients were divided into 4 groups, 22 in L group, 23 in B and S group while 22 in H group respectively. The RR of the groups were 68.2%, 26.1%, 30.4% and 22.7% respectively. There were statistically significant differences between L group and other 3 groups (P <0.05). The MST were 377, 305, 321 and 271 days respectively, and the TTP were 240, 182, 190 and 166 days in the 4 groups. Statistically significant differences between L group and other 3 groups (P <0.05) can be seen in both MST and TTP. The expression of beta-tubulin-III and Stathmin in advanced NSCLC biopsies had relationship with the sensitivity to NP chemotherapy regimen in the patients. Cases with high level of these two proteins would have poor responses to this cytotoxic drug.

Intratumoral injection of dendritic cells in combination with local hyperthermia induces systemic antitumor effect in patients with advanced melanoma

Dendritic cells (DC) are potent antigen-presenting cells that can present tumor antigens chaperoned by heat shock proteins (HSPs), while local hyperthermia (LHT) can increase the expression of HSPs. In this study, we determine if intratumoral injection of immature DC after LHT (LHT+IT-DC) induces systemic antitumor immunity in patients with advanced melanoma, and investigate the potential immunological mechanisms involved in the treatments. Patients were randomly assigned to intratumoral administration of autologous immature DC triweekly, with (LHT+IT-DC, arm A, n = 9) or without (IT-DC, arm B, n = 9) LHT. Our results showed that there were no grade 3/4 toxicities. The time to progress (TTP) of arm A was 5 months, significantly longer than that in arm B (2 months, p < 0.05). However, the overall survival time had no statistical difference (13 months vs. 6 months, p > 0.05) between the 2 groups. Our ELISPOT assay showed a significantly increased melanoma-specific IFN-gamma production in arm A, suggesting that LHT+IT-DC was more effective in the induction of cytotoxic T lymphocytes (CTL) than IT-DC alone. Furthermore, we detected an increased HSPs expression 4 hr after the first LHT, an enhanced Th1/Th2 chemokines production 24 hr after the first LHT+IT-DC treatment, a promoted migration of DC to afferent lymph nodes, and a decreased infiltration of regulatory T cells (CD4(+)CD25(+)) and an increased infiltration of active CTL (CD8(+)CD28(+)) 48 hr after the third DC injection in arm A patients. Therefore, LHT+IT-DC can induce effective specific antitumor immunity and facilitate a Th1-polarized immune response in patients with advanced melanoma.

K-ras and EGFR mutations in 24 Chinese patients with non-small-cell lung cancer (NSCLC) treated with gefitinib

17109 Background: It was previously reported that K-ras mutations could behave as a resistance marker for response to gefitinib while EGFR mutations make NSCLC more responsive to this medication. And it is known that Asians and Westerners have different responses to gefitinib. Therefore, we are to identify the mutational status of K-ras and EGFR in the group of Chinese patients with NSCLC especially adenocarcinoma treated with gefitinib to find some helpful information. Methods: Genomic DNA was extracted from tumor specimens, including liquid nitrogen frozen tumor, paraffin blocks and fine needle biopsies from 24 patients with advanced NSCLC, who failed at least one platinum-based regimen, treated with gefitinib. Nested polymerase chain reaction products of codons 12, 13, 59, and 61 of K-ras and exon 18 through 21 of EGFR were directly sequenced at least twice. Results: Patients’ age ranges from 24 to 71 years (54.8 ± 10.2). Male/female was 14/10. Thirteen patients were smokers and 11 were non-smokers. Eighteen were adenocarcinomas, 2 were bronchioloalveolar carcinomas, 2 were squamous cell carcinomas and 2 were large cell carcinomas. The disease control (CR+PR+SD) rate was 79.2% (19/24) and the objective response (CR+PR) rate was 50.0% (12/24). No K-ras gene mutation was found in all patients. Fifteen patients (62.5%, 15/24) harbored EGFR mutations, which were delE746-A750 (8), delE746-A751 (1), delE746-A751insA (1), L861Q (1), L858R (5) and A871G (1). Two patients had double mutations (delE746-A750 and L858R). The disease control rate for wild type and mutant EGFR were 66.7% (6/9) and 86.7% (13/15), and the objective response rate were 33.3% (3/9) and 60.0% (9/15). Median time to progress (TTP) for wild type and mutant EGFR were 439 days (SE 249.8) and 367 days (SE 108.8). However, no statistically significant differences were found between these two groups regarding the response rates and TTP. Conclusions: K-ras mutation may occur at a low frequency in Chinese NSCLC groups despite the pathology, status of smoking, gender and EGFR mutations. And the relationship between the response to gefitinib and K-ras mutation might still remain to be determined at least in Chinese NSCLC. And the role of EGFR mutations in prediction of response to gefitinib should be further studied. No significant financial relationships to disclose.