[Significance of expression of chemokine receptor and matrix metalloproteinase in small cell lung cancer].

OBJECTIVE: To explore the expressions of CXC chemokine receptor 4 (CXCR4) and matrix metalloproteinase-9 (MMP-9) and examine their correlations with metastasis and prognosis in small cell lung cancer (SCLC). METHODS: Immunohistochemistry was employed to detect the expressions of CXCR4 and MMP-9 in the tissue samples from 65 SCLC patients treated in Cancer Institute and Hospital Attached to Tianjin Medical University from January 2003 to October 2009. And their correlations with metastasis and prognosis were analyzed by Chi-square test and Kaplan-Meier method and Cox regression. RESULTS: The positive expression rates of CXCR4 and MMP-9 were 100.0% (65/65) and 87.7% (57/65) in SCLC tissues respectively. Significant difference of the expression rate of CXCR4 was found between patients undergoing bone metastasis or not (P = 0.004). But the differences were not significant between brain metastasis or not (P = 0.068) and lymph node metastasis or not (P = 0.085). A high expression rate of MMP-9 was significantly associated with pathological staging (P = 0.048). But the difference between lymph node metastasis or not was not significant (P = 0.085). Univariate analysis suggested that a high expression rate of CXCR4 was significantly correlated with the disease-free survival (DFS) of SCLC patients (P = 0.005). But a high expression rate of MMP-9 was not associated with DFS (P = 0.341). Multivariate analysis suggested that a high expression rate of CXCR4 was an independent prognostic factor for DFS in SCLC. CONCLUSIONS: The elevated levels of CXCR4 and MMP-9 are found in SCLC tissues. And the expression rate of CXCR4 may be correlated with bone metastasis, but the correlation is not notable for MMP-9. The expression rate of CXCR4 is an independent prognostic factor for DFS in SCLC.

Thoracic radiotherapy (TRT) improved survival in both oligo- and polymetastatic extensive stage small cell lung cancer.

There has been no previous study on the efficacy of the thoracic radiotherapy (TRT) in oligometastatic or polymetastatic extensive stage small-cell lung cancer (ES-SCLC) to the overall survival (OS). In a group of 270 ES-SCLC cases retrospective study, 78 patients (28.9%) had oligometastases and 192 (71.1%) had polymetastases, among which 51 oligometastatic patients (65.4%) and 93 polymetastatic patients (51.6%) received TRT. Propensity score matching (PSM) was utilized. The 2-year OS, progression free survival (PFS) and local control (LC) in oligometastatic and polymetastatic patients were 22.8% and 4.5% (p < 0.001), 12.0% and 3.8% (p < 0.001), and 36.7% and 6.1% (p < 0.001), respectively. The 2-year OS in oligometastatic patients with the chemotherapy + radiotherapy and chemotherapy alone were 25.2% and 12.7% (p = 0.002), in contrast to 10.0% and 6.8% (p = 0.030) in polymetastatic patients. The estimated hazard ratios for survival were 2.9 and 1.7 for both oligometastatic and polymetastatic patients with radiotherapy. The polymetastatic group has a lower LC (6.1% v.s. 36.7%, (p < 0.001)), due to polymetastases patients receiving involved-sites radiotherapy with low dose schemas. TRT improved OS of patients with oligometastases and polymetastases. Our study demonstrated that aggressive TRT might be a suitable addition of chemotherapy when treating ES-SCLC patients with oligometastases and polymetastases.

Receipt of thoracic radiation therapy and radiotherapy dose are correlated with outcomes in a retrospective study of three hundred and six patients with extensive stage small-cell lung cancer.

BACKGROUND: The importance of the thoracic radiation therapy (TRT) dose has not been clearly defined in extensive stage small-cell lung cancer (ES-SCLC) and it is unclear whether improved TRT dose translates into a survival benefit. METHODS: 306 patients with ES-SCLC were retrospectively reviewed, of which 170 received IMRT/CRT fractionation RT after ChT, and 136 received chemotherapy (ChT) alone. We adopted the time-adjusted BED (tBED) for effective dose fractionation calculation. Due to the nonrandomized nature of this study, we compared the ChT+RT with ChT groups that matched on possible confounding variables. RESULTS: Patients achieved 2-year OS, PFS and LC rates of 19.7%, 10.7% and 28.4%, respectively. After propensity score matching, (113 cases for each group), the rates of OS, PFS and LC at 2 years were 21.4%, 7.7% and 34.5% for ChT+TRT, and 10.3% (p<0.001), 4.6% (p<0.001) and 6.3% for ChT only (p<0.001), respectively. Among propensity score matching patients, 56 cases for each group received the high dose (tBED>50 Gy) TRT and received low dose (tBED≤50 Gy) TRT. Two-year OS, PFS and LC rates were 32.3%, 15.3% and 47.1% for the high dose compared with 17.0% (p<0.001), 12.9% (p=0.097) and 34.7% (p=0.029) for low dose radiotherapy. CONCLUSIONS: TRT added to ChT improved ES-SCLC patient OS. High dose TRT improved OS over lower doses. Our results suggest that high-dose thoracic radiation therapy may be a reasonable consideration in select patients with ES-SCLC.

Characterization of polymorphic microsatellite markers in Pinus armandii (Pinaceae), an endemic conifer species to China.

PREMISE OF THE STUDY: Pinus armandii (Pinaceae) is an important conifer tree species in central and southwestern China, and it plays a key role in the local forest ecosystems. To investigate its population genetics and design effective conservation strategies, we characterized 18 polymorphic microsatellite markers for this species. METHODS AND RESULTS: Eighteen novel polymorphic and 16 monomorphic microsatellite loci of P. armandii were isolated using Illumina MiSeq technology. The number of alleles per locus ranged from two to five. The expected heterozygosity ranged from 0.061 to 0.609 with an average of 0.384, and the observed heterozygosity ranged from 0.063 to 0.947 with an average of 0.436. Seventeen loci could be successfully transferred to five related Pinus species (P. koraiensis, P. griffithii, P. sibirica, P. pumila, and P. bungeana). CONCLUSIONS: These novel microsatellites could potentially be used to investigate the population genetics of P. armandii and related species.

[Expression of aurora-A kinase in human lung cancer cell lines PG, A549, and NCI-H460].

BACKGROUND & OBJECTIVE: Recent researches found that Aurora-A overexpresses in various malignancies. This study was to detect the expression of Aurora-A in lung cancer cell lines PG (highly-metastatic giant cell lung cancer), A549 (lung adenocarcinoma), and NCI-H460 (large cell lung cancer) and explore its correlation to DNA content, provide a theoretical basis for screening tumor marker and molecular therapeutic target of lung cancer. METHODS: mRNA and protein levels of Aurora-A in PG, A549, and NCI-H460 cells were detected by reverse transcription-polymerase chain reaction(RT-PCR) and Western blot. Flow cytometry was used to analyze DNA contents in cell cycles of PG, A549, and NCI-H460 cells. RESULTS: mRNA level of Aurora-A was 1.14 in PG cells, 1.16 in A549 cells, and 0.84 in NCI-H460 cells, respectively; protein level of Aurora-A was 8.96 in PG cells, 21.13 in A549 cells, and 6.43 in NCI-H460 cells, respectively. The proportion of cells with tetraploid DNA was 19.88% in PG cells, 14.97% in A549 cells, and 10.6% in NCI-H460 cells, respectively (P<0.01); the proportion of cells with polyploid DNA was 2.66% in PG cells, 3.59% in A549 cells, and 2.30% in NCI-H460 cells, respectively. CONCLUSION: Aurora-A is overexpressed in the 3 lung cancer cell lines, but the mRNA levels are different.