FOLFOX/XELOX plus cetuximab administered weekly versus biweekly as a first-line treatment for patients with KRAS/RAS wild-type metastatic colorectal cancer: a retro-spective study / 中国肿瘤临床

To compare the efficacy and safety of cetuximab biweekly regimen with those of standard weekly regimen as a first-line therapy of KRAS/RAS wild-type metastatic colorectal cancer. Methods: Patients who received weekly or biweekly administra-tion of cetuximab plus FOLFOX/XELOX as a first-line therapy from July 2010 to December 2017 in Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively screened for eligibility. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and frequencies of adverse events (AEs) between the two groups were compared. Results: Of 152 eligible patients, 55 were in the biweekly group and 43 were in the weekly group. The biweekly group had significantly higher ORR than the weekly group (76.3% vs. 54.8%, P=0.025). Median PFS in the biweekly and weekly groups were 10.3 and 8.8 months, respectively (P=0.288), and the median OS were 33.5 and 27.4 months, respectively (P=0.563). The two groups showed no significant difference in PFS and OS. For overall AEs, the biweekly group presented significantly more stomatitis (32.7% vs. 14.0% , P=0.032) and tended to show substantially more acne-like rash (80.0% vs. 62.8%, P=0.058) and leukopenia and/or neutropenia (72.7% vs. 55.8%, P=0.081). The frequency of 3/4 grade acne-like rash in the biweekly and weekly groups were 18.2% and 7.0%, respectively (P=0.105). The frequency of all grade 3/4 AEs between the two groups showed no significant difference (P>0.05). Conclusions: Biweekly regimen of cetuximab plus FOLFOX/XE-LOX had similar efficacy and higher ORR compared with those of standard weekly regimen. Cetuximab administered biweekly may be an optional choice in clinical practice, with close attention paid to increased frequency of certain AEs.

Application of circulating tumor DNA in endocrine therapy resistance of breast cancer / 国际肿瘤学杂志

Although most hormone-receptor positive breast cancer patients initially respond to endocrine treatment,they will eventually acquire resistance to endocrine therapy.Therefore,during clinical treatment,it is of great importance to continuously monitor for resistant mutations.Circulating tumor DNA (ctDNA) has become more prevalent because it is non-invasive,convenient,rapid,and can quickly assess the overall situation of the tumor.With the maturity of next-generation sequencing (NGS) and droplet digital polymerase chain reaction (ddPCR),the establishment of endocrine treatment resistance mutation monitoring system has become possible.

Advances in the treatment for HER2-positive advanced gastric cancer / 中国肿瘤临床

The addition of HER2-targeted therapy has markedly improved the survival and prognosis of patients with advanced gastric cancer. Inhibiting the HER2 signaling pathway has become the backbone treatment for advanced HER2-positive gastric cancer in the first-line setting. TOGA trial established trastuzumab in combination with cisplatin and 5-flurouracil as the standard first-line treat-ment. In the post-TOGA era, combinations of trastuzumab with other chemotherapy agents were proven to be effective as both the second-line treatment and the conversion treatment. Such combinations are promising in the neoadjuvant treatment for locally ad-vanced gastric cancer. Research focuses on the development of novel anti-HER2 agents in combination with agents targeting against other signal pathways. Real-time monitoring of the gene expression profile is the key to discovering the mechanism of trastuzumab re-sistance. The preliminary results of existing clinical trials have shown potential to overcome resistance to trastuzumab. In this review, we summarized the treatment advancement for HER2 positive gastric cancer and the direction for future development, thereby provid-ing guidance on clinical practice.

Family physician integrated health care plan and payment system in Taiwan Province / 中国卫生政策研究

Under National Health Insurance system ( NHI) , Taiwan implemented “Family Physician Integrat-ed Health care Plan” by focusing on the key functions of primary medical institutions and family physicians. This plan had continuously strengthened the family physician system and the quality of integrated health care provision. Taiwan’s achievements and experiences were valuable for Mainland China. This paper first introduced the health sys-tem and health care provision system of primary medical institutions in Taiwan from the aspects of financing, pay-ment, health care delivery system structure, and market-capture institutions. Then, we made a comprehensive intro-duction on the policy objectives, organization structures, operation system, service schemes and health insurance pay-ment system of this plan. Finally we proposed the suggestion for integrated health care provision system in Mainland China. It is of vital importance that government should design the integrated service provision system by focusing on the key functions of family physicians. It is also of equal significance that the health administrative departments should cooperate with health insurance administrative departments to gain sufficient policy and funding resources for the plan’s successful implementation.

Clinical analysis of extraction methods of impacted mandibular third molars 486 cases report / 中国基层医药

Objective To investigate the indication of turbine technique or hammer and chisel technique removral of impacted mandibular third molars.Methods 486 impacted mandibular third molars patients were randomly divided into two treatment groups.One group received turbine technigue of 199 cases.while another group received hammer and chisel technique of 287 cases.Both the duration of operation and complications were compared.Results The average duration of the operation with turbine technique was(10 ～ 45)min,while with hammer and chisel technique was(12 ～ 90)min,respectively(P ＜ 0.05)in the removal of impacted mandibalar third molars.there were significant differences between two groups.The standardized rate of complication with tubine tehnique was 28.8％,while with hammer and clisel technique was 55.1％ in the remoral of impacted mandibular third molars.Conclusion Extraction of impacted mandi-bular third molars with air turbine hand piece could reduce complication during operation,and risperidone showed better results.It is worth for clinical use.

Effects of ST2325 on HER2/neu tyrosine kinase signal pathway and on cell cycle arrest in breast cancer BT474 cells / 中国药理学通报

Aim The aim of this study is to determine effect of ST2325 on HER2/neu tyrosine kinase signal pathway and cell cycle in breast cancer BT474 cells. Methods Protein expression was detected with immunoblot analysis. Cell cycle distribution was examined using flow cytometry.Results ST2325 inhibited tyrosine phosphorylation of HER-2/neu in a dose-dependent manner with half maximal inhibition occurring at a concentration of 8.7 ?mol?L -1 without reduced HER-2/neu receptor protein expression. Activation of MAPK and AKT, downstream molecules of HER-2/neu-mediated signal transduction pathway was inhibited following exposure to ST2325. After BT474 cells were treated with different concentrations of ST2325 for 24 h, the results of flow cytometry analysis showed cell cycle arrest in G 1 phase. Western blot assay showed up-regulation of p27 protein expression and decrease of hyperphosphorylated Rb and cyclin D1 protein expression.Conclusions ST2325 inhibits HER2 tyrosine kinase phosphorylation and induces G 1 arrest in BT474 cells. Cell cycle arrest in G 1 is associated with p27 up-regulation, decrease of cyclin D1 protein and hyperphosphorylated Rb.

Rapid tissue microarray assay of p16 protein expression for different stage nasopharyngeal carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To effectively screen p16 protein expression of different clinical stage nasopharyngeal carcinoma (NPC) by constructing and applying high-throughput tissue microarray/tissue chip.</p><p><b>METHODS</b>A series of tissue chips were prepared by using tissue arrayer with samples from different clinical stage NPC tumors and noncancerous nasopharynx tissue. Specimens from 259 cases of nasopharyngeal lesions were detected immunohistochemically on a tissue chip for p16 protein expression and the correlation of p16 protein expression to clinical stage of NPC was analyzed statistically.</p><p><b>RESULTS</b>p16 protein expression was detected in all 18 histologically normal nasopharyngeal epithelia. No p16 protein was detected in 3 of 3 (100%) stage I NPC, 38 of 44 (86.3%) stage II NPC, 59 of 68 (86.8%) stage III NPC, 23 of 28 (82.1%) stage IV NPC, 87 of 98 (88.8%) unclear stage NPC. The efficiency of p16 protein expression in NPC tissues was significantly lower than that in normal nasopharyngeal epithelia (chi(2) = 82.58, P < 0.001), and there was no apparent relationship between p16 protein expression and clinical stages (chi(2) = 0.09, P = 0.769).</p><p><b>CONCLUSIONS</b>The frequent deletion of p16 protein in NPC suggests that p16 gene has an important role in the development and progression of NPC. The consistency of p16 protein deletion in different stages of NPC suggests that the deletion of p16 protein is an early event in the development of NPC, and it is feasible to utilize tissue microarray for a rapid, economic and accurate screening of clinical tissue specimens on a large scale.</p>

High frequency loss of heterozygosity on the long arms of chromosomes 13 and 14 in nasopharyngeal carcinoma in Southern China / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the loss of heterozygosity (LOH) on chromosomal arms 13q and 14q in nasopharyngeal carcinoma (NPC) using 21 microsatellite polymorphic markers and to study whether there is a correlation between LOH and clinicopathologic parameters and/or Epstein-Barr virus (EBV) infection in NPC.</p><p><b>METHODS</b>Sixty cases of NPC were studied using polymerase chain reaction based microsatellite analysis with genescan and genotyping techniques.</p><p><b>RESULTS</b>LOH was detected on 13q in 78% of NPC tumors, high frequency LOH loci (more than 30%) clustered to 13q12.3-q14.3 and 13q32. On chromosome 14q, LOH was detected in 80% of NPC tumors; high frequency LOH loci clustered to 14q11-q13, 14q21-q24 and 14q32. High frequency LOH at 13q31-q32 correlated with a lower level of EBV infection; LOH on chromosome 14q was closely associated with poor differentiation of NPC tumor cells.</p><p><b>CONCLUSION</b>Our results suggest that in NPC, LOH on chromosome 13q and 14q are common genetic events, and putative tumor suppressor genes (TSG) residing in these regions may be involved in tumorigenesis.</p>

Differentially expressed gene in nasopharyngeal carcinoma cell lines with various metastatic potentialities / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate gene expression profile in nasopharyngeaL carcinoma (NPC) cell lines with different metastatic potentialities, in order to identify new candidate genes related to the development, progress and metastasis of NPC.</p><p><b>METHODS</b>The mRNA expressions of high metastatic NPC cell line 5-8F, tumorigenic but nonmetastatic NPC cell line 6-10B and non-tumorigenic NPC cell line 13-9B (3 sublines of SUNE-1) were investigated by cDNA microarray containing 14 000 cDNA clones. The alterations in gene expression levels were confirmed by reverse-transcription PCR.</p><p><b>RESULTS</b>There were 82 differentially expressed genes comparing 5-8F and 13-9B; 38 differentially expressed genes comparing 6-10B and 13-9B; 54 comparing 5-8F and 6-10B. There were 12 common differentially expressed genes comparing 6-10B, 5-8F and 13-9B; 14 common differentially expressed genes comparing 5-8F and 13-9B, 6-10B. The expressions of the above genes were involved in metabolism, transcription, differentiation, apoptosis and signal transduction.</p><p><b>CONCLUSION</b>The gene expression profile in nasopharyngeal carcinoma cell lines is an important index in the search of new candidate genes related to NPC.</p>

Effect of ST2325 on cell cycle in erbB2-overexpressing breast cancer MDA-MB-453m1 cells and its mechanism / 中国癌症杂志

Purpose：Effect of ST2325 on cell cycle in erbB2-overexpressing MDA-MB-453m1 cells and its mechanism was investigated.Methods：Cell cycle distribution was examined using flow cytometry. The protein expression was detected with Western blot analysis.Results：Under concentrations of 0,6.25,12.5,25.0,50.0,100 μmol/L，the percentrages of G0/G1 in MDA-MB-453m1 were 48.62%, 48.83%, 49.59%, 52.18%, 61.0%,83.96%; the percentages of S were 33.34%, 33.16%, 32.78%,30.77%,25.62%,7.08%;the percentages of G2M were 18.04%, 18.01%,17.63%,17.05%,13.38%,8.96%.After MDA-MB-453m1 cells were treated with different concentrations of ST2325 for 24 hours, Western blot assay showed up-regulation of p27 protein expression and decrease of hyperphosphorylated Rb and cyclin D1 protein expression .Activation of MAPK and AKT in MDA-MB-453m1 was markedly inhibited by ST2325.Conclusions：ST2325 induces G1 arrest in erbB2-overexpressing MDA-MB-453m1 cancer cells. G1 arrest is associated with p27 upregulation,decrease of cyclinD1 protein and hyperphosphorylated Rb.