Analysis of therapeutic effect and prognosis in patients with metastatic colorectal cancer and different K-ras status / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the correlation of clinical effect and prognosis between patients with metastatic colorectal cancer (mCRC) and different K-ras status.</p><p><b>METHODS</b>The clinical characteristics, chemotherapeutic regimens and survival of 153 mCRC patients with different K-ras status were analyzed retrospectively.</p><p><b>RESULTS</b>The median overall survival (OS) in patients without K-ras mutation were 31.7 months, significantly longer than 21.3 months in the patients with K-ras mutation (P = 0.037). The median progression-free survival (PFS) and OS in patients who received chemotherapy followed by anti-EGFR antibody treatment were 11.5 and 39.3 months, respectively, significantly longer as compared with the PFS and OS in those received chemotherapy in combination with anti-EGFR antibody concomitantly (5.7, P = 0.02, and 28.7 months, P = 0.034, respectively).</p><p><b>CONCLUSIONS</b>K-ras status is a prognostic biomarker for mCRC patients treated with anti-EGFR antibody. The combination settings of anti-EGFR in combination with chemotherapy may improve survival of mCRC patients with wild-type K-ras status.</p>

Correlation analysis between abundance of K-ras mutation in plasma free DNA and its correlation with clinical outcome and prognosis in patients with metastatic colorectal cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To detect K-ras gene mutations in plasma free DNA by peptide nucleic acid clamp PCR assay (PNA-PCR) and nested primer PCR, and to analyze the correlation between K-ras mutations and prognosis in patients with metastatic colorectal cancer (mCRC).</p><p><b>METHODS</b>Peripheral blood was collected and free DNA was extracted from plasma in 106 patients with mCRC. Nested primer PCR and PNA-PCR were used to detect K-ras gene mutation in the plasma free DNA. The patients were divided into three groups by K-ras status: wild-type group (wild-type determined by both methods), low mutation group (mutation by PNA-PCR method, wild-type by nested primer PCR method) and high mutation group (mutation by two methods). The correlation between K-ras mutations and prognosis was analyzed.</p><p><b>RESULTS</b>The mutation rate of K-ras in tumor tissues of the 106 patients was 40.6%. The Mutation rate of K-ras in plasma free DNA detected by PNA-PCR was 31.1%, significantly higher than that of 15.1% detected by nested primer PCR (P = 0.006). The consistent rate of the K-ras status in plasma free DNA detected by PNA-PCR and that in tumor tissue detected by traditional method was up to 83.0%. The median overall survival (OS) of patients of the wild type, low mutation and high mutation groups was 23.5 months, 17.3 months and 13.9 months, respectively (P = 0.002). The median progression-free survival (PFS) of the K-ras wild-type, low mutation and high mutation groups with first-line chemotherapy was 6.8 months, 6.1 months and 3.2 months, respectively (P = 0.002), and the median OS of them were 23.0 months, 15.5 months and 13.9 months, respectively (P = 0.036). The overall response rate (ORR) was improved in the K-ras wide-type patients who received cetuximab combined with chemotherapy as first-line therapy (75.0% vs. 23.4%, P = 0.058). Cetuximab combined with in second-line therapy chemotherapy led to a significant improvement in disease control rate (DCR) ( 100% vs. 35.7%, P < 0.001) as compared with those of chemotherapy alone. COX regression model showed that K-ras status detected by PNA-PCR, ECOG PS, number of surgery and initially metastatic site were independent factors for prognosis.</p><p><b>CONCLUSIONS</b>PNA-PCR for the detection of K-ras mutation in plasma free DNA can be used to substitute the traditional method for detection of K-ras mutation in tumor tissues. The abundance of K-ras mutation in plasma free DNA is an independent prognostic factor for patients with metastatic colorectal cancer.</p>

Expression of Osterix mRNA and protein levels in cultured human periodontal ligament cells after mechanical stimulation / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To examine the expression of Osterix (Osx) mRNA and protein after application of mechanical force on human periodontal ligament cells (HPDLCs), and to investigate the role of Osx in orthodontic alveolar bone remodeling.</p><p><b>METHODS</b>HPDLCs were isolated and cultured in vitro with explant method. Approximately 2.5 x 10(5) cells were seeded onto six-well cell culture plates and then were exposed to centrifugal force for 1, 2, 4, 6, 8 or 12 h at 631 r x min(-1). The expression of Osx mRNA and protein was measured by reverse transcription-polymerase chain raction (RT-PCR) and Western blot respectively. Immunofluorescence assay was used to detect the expression and subcellular At the initial time point, Osx mRNA had a weak exlocalization of Osx protein by green fluorescence.</p><p><b>RESULTS</b>pression and protein was not detected. Under the mechanical stimulation, both mRNA and protein levels of Osx were upregulated in a time-dependent manner. Furthermore, Osx protein was translocated gradually from the cytosol into the cell nuclei.</p><p><b>CONCLUSION</b>The expression and activation of Osx were enhanced by mechanical stress in HPDLCs, which indicates that Osx may play an important role in HPDLCs osteogenic differentiation and periodontal tissue remodeling induced by mechanical stress.</p>