Predictive Value of Tumor Mutation Burden in Immunotherapy for Lung Cancer / 中国肺癌杂志

The morbidity and mortality of lung cancer is the first in the world, immunotherapy has become a important treatment strategy in addition to chemotherapy, radiotherapy and targeted therapy. In recent years, the US Food and Drug Administration (FDA) has successively approved immunological checkpoint inhibitors as standard programs for non-small cell lung cancer (NSCLC) in second-line or first-line treatment. The National Comprehensive Cancer Network (NCCN) also recommends immunological checkpoint inhibitors as the standard treatment for small cell lung cancer (SCLC). Now, the treatment for lung cancer has entered the era of precision treatment, it is very important to select effective and reliable biomarker for the dominant populations of lung cancer to receive immunotherapy. A large number of researchs indicated that tumor mutation burden (TMB) may be an independent predicted biomarker for immunotherapy, but with limitations. This article reviewed the predictive value of TMB and its limitations in the field of immunotherapy for lung cancer.

Progression of diagnosis and treatment for adenosquamous lung carcinoma / 中华肿瘤杂志

Adenosquamous lung carcinoma (ASC) is an uncommon entity of the primary lung cancer, which is mixed by adenocarcinoma and squamous carcinoma cells. ASC not only possesses the malignant biological characteristics of adenocarcinoma and squamous cell carcinoma, but also exhibits special clinical features, such as the higher malignant degree and poorer prognosis. This paper is aimed to elaborate the research process of the pathological origin of ASC, the application of different diagnostic methods in ASC, various therapeutic strategies and its associated prognosis so as to help to develop the clinical strategies of ASC.

Combinational immunological checkpoint inhibitors for non-small cell lung cancer / 国际肿瘤学杂志

Immunological checkpoint inhibitors have become one of the major treatment options for patients with advanced non-small cell lung cancer (NSCLC).Despite patients with NSCLC show the superiority of standard chemotherapy in different disease settings,the response rate is still low in patients with high macromolecule selection for chemotherapy tolerance and gene mutation.This is related to the complexity and dynamics of known limited biomarkers and tumor microenvironment.Different methods of tumor cells to evade the immune system used to lay the foundation for the new combination strategy.Combination therapy not only improves the efficacy of treatment,but also makes the objective response rate improved significantly.

Progress of ALK gene inhibitors in the treatment of brain metastases from non-small cell lung cancer / 国际肿瘤学杂志

Anaplastic lymphoma kinase (ALK) rearrangement is one of the most potent carcinogenic genes in non-small cell lung cancer (NSCLC).The first-generation ALK inhibitor such as crizotinib is superior to chemotherapy for NSCLC patients with ALK rearrangement.At the same time,more and more studies have reported ALK inhibitors in brain metastases of NSCLC patients with intracranial efficiency.However,despite the initial clinical data of first-generation ALK inhibitors in the treatment of ALK-positive NSCLC with brain metastases,different degrees of recurrence of tumors after acquired resistance have posed new challenges for follow-up treatment of cancer patients.A new generation of ALK inhibitors,such as alectinib;ceritinib,AP26113 and PF-06463922 have emerged to solve this problem.

Efficacy of adjuvant therapy in 110 patients with N1 lymph node metastasis of esophageal squamous cell carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to evaluate the effect of postoperative adjuvant therapy on the survival in patients with N1 lymph node metastasis of esophageal squamous cell carcinoma (ESCC).</p><p><b>METHODS</b>110 patients with positive N1 lymph node metastasis of esophageal squamous carcinoma were included in this study. The surgery group included 46 cases and the postoperative adjuvant therapy group included 64 cases (24 cases in the adjuvant chemotherapy subgroup and 40 cases in the adjuvant concurrent chemoradiotherapy). The disease-free survival (DFS) and overall survival (OS) of the two groups were compared and the prognostic factors were analyzed by multivariate Cox model.</p><p><b>RESULTS</b>In the postoperative adjuvant therapy group, the DFS (16.8 months) and OS (21.3 months) were significantly prolonged compared with those in the surgery group (10.6 months, P=0.007) and (13.7 months, P=0.001), respectively. Postoperative adjuvant chemotherapy significantly extended the OS (31.1 months) of N1-positive patients compared with 13.7 months (P=0.002) in the surgery group. But there were no significant differences between the DFS in the two subgroups (16.3 and 16.8 months, P=0.346) and between the OS (23.4 and 21.3 months, P=0.491). Postoperative adjuvant therapy was an independent prognostic factor in the ESCC patients with N1 lymph node metastasis.</p><p><b>CONCLUSION</b>Postoperative adjuvant therapy can improve the prognosis and prolong the survival time in ESCC patients with positive N1 lymph node metastasis.</p>

Progress in treatment of acute kidney injure with adipose-derived mesenchymal stem cells / 中国医师杂志

Cell-based therapy and regenerative medicine offer a paradigm shift in regard to various diseases causing tissue or organ damage.Recently,many authors have focused their atte(n)tion on adipose-derived mesenchymal stem cells (ADMSCs) for their capacity to differentiate into many cell lineages.Acute kidney injury (AKI),as a common emergency,has high morbidity rate and relatively limited treatment.This review will summarize the mechanism of ADMSCs in treatment of acute kidney injury,and hope to lay a foundation for future research.

Clinical value of NLR combined with PSA in the early diagnosis of prostate carcinoma / 中国基层医药

Objective To discuss the significance of the application of neutrophil to lymphocyte ratio (NLR)combined with prostate specific antigen (PSA)in early diagnosis of prostate carcinoma.Methods 120 cases with surgery treatment of prostate carcinoma were selected as study group,and 120 healthy people were selected as control groups.The NLR and PSA were tested to diagnose the prostate carcinoma.The critical value of NLR in diagnosing prostate carcinoma was evaluated by ROC curves,and the advantages of combination of NLR and PSA were judged. Results By using ROC curves to evaluate the NLR in diagnosis,the critical value was 2.75.The susceptibility, specificity,Youden index,correct index were 0.79,0.85,0.65,0.72.The susceptibility,specificity,positive predictive value,negative predictive value,correct index of NLR combined with PSA in diagnosing the prostate carcinoma were 0.85,0.83,5.00,0.18,0.68.Conclusion The application of NLR has higher susceptibility and specificity to diagnose prostate carcinoma.NLR combined with PSA can improve the susceptibility and specificity of early diagnosis of prostate carcinoma.

Relationship between the efficacy of gemcitabine/cisplatin adjuvant chemotherapy and RRM1 protein expression in postoperative NSCLC patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The purpose of this study was to investigate the relationship between the expression of ribonucleotide reductase subunit M1 (RRM1) protein and the efficacy of gemcitabine/cisplatin (GP) adjuvant chemotherapy in postoperative non-small cell lung cancer (NSCLC) patients.</p><p><b>METHODS</b>A total of 68 patients with NSCLC after radical surgery were included in this study. The expression of RRM1 protein in tumor specimens was assayed by streptavidin-peroxidase (SP) immunohistochemistry retrospectively. Correlation between the expression of RRM1 protein and the efficacy of GP chemotherapy was analyzed. Disease-free survival rate was taken as the main outcome measure.</p><p><b>RESULTS</b>Among the 68 patients, 31 cases had recurrence or metastasis. The expression rate of RRM1 was 54.4%. The 1-year and 3-year disease-free survival rates were 82.7% and 61.5% for patients with RRM1-negative expression, and 78.1% and 36.8% for patients with RRM1-posivive expression, respectively (P = 0.044). In the subgroup analysis of stage IB cases, the 1-year and 3-year disease-free survival rates were 100% and 82.3% for patients with RRM1-negative expression, and 84.5% and 24.6% for patients with RRM1-positive expression, respectively (P = 0.047). In the analysis of squamous cell carcinoma subgroup, the 1-year and 3-year disease-free survival rates were 92.3% and 83.7% for patients with RRM1-negative expression, and 83.1% and 43.9% for patients with RRM1-posivive expression, respectively (P = 0.005). Univariate analysis and multivariate analysis indicated that smoking history, pathological type, clinical stage and expression of RRM1 significantly influenced the therapeutic efficacy (P < 0.05).</p><p><b>CONCLUSIONS</b>RRM1 protein may be a valuable predictive factor for gemcitabine/cisplatin adjuvant chemotherapy in NSCLC patients.</p>

Pathological features of 59 cases of resected lung adenosquamous carcinoma impact on patient survival / 中华胸心血管外科杂志

Objective To explore the pathological features affecting the prognosis by observing lung adenosquamous carcinoma overall survival after surgical treatment.Methods Totally 59 cases of lung ASC from 2531 surgically treated lung cancer patients in the First Hospital of Jilin University,from January 2000 to June 2012,were retrospectively analyzed to study their clinical characteristics,survival condition and the related factors influencing the prognosis.Using log-rank test and Cox multiple factors analysis for statistical analysis.Results (1) The 59 patients with ASC were mostly the male patients (62.7％).The median age was 57.2 years.Median survival time was 409 days(13.6 months).1-,3-,5-year survival rates were 59.9 ％,36.4％ and 31.2 ％.(2) Among the 59 patients (52 cases of pathological specimens),11 cases were EGFR mutation positive,positive rate was 21.2％,2 cases of patients were KRAS mutations positive,positive rate was 3.8％ ;(3) Single factor and multiple factors analysis showed that the pathological subtype,adjuvant treatment,pleural invasion and tumor stage were associated with prognosis as independent factors (P ＜ 0.05).Conclusion Compared with the simplex lung squamous carcinoma and lung adenocarcinoma,lung adenosquamous carcinoma has poorer prognosis.Early diagnosis and given comprehensive treatment were the keys to prolong its survival.

Acetylated myocyte enhancer factor-2D can promote T cell apoptosis by regulating the expression of Nur77 / 中国组织工程研究

AIM: Nur77 expression can lead to T cell apoptosis, and it is activated by the second messenger calcium. The calcium-responsive elements in the Nur77 promoter are two putative binding sites for the transcription factor, myocyte enhancer factor-2D (MEF2D). In this study, we explored whether MEF2D could be acetylated in Nur77-induced T cell apoptosis and whether MEF2D acetylation was affected by the regulation of Nur77 expression. METHODS: The experiment was performed at Department of Hematology-Oncology in the First Hospital of Jilin University from November 2006 to September 2007. ①Escherichia coli DH5?and plasmid pcDNA3 were held by the Research Center in the First Hospital of Jilin University. Plasmids pET32M, Flag-p300 and pSilencerTM-p300 RNAi were gifts from Professor Zhengguo Wu from Hong Kong University of Science and Technology. Plasmid NFATp was contributed by Yun Chen from Harvard University. Jurkat cells were provided by Department of Hematology- Oncology in the First Hospital of Jilin University. ②The full-length Nur77 gene, generated by PCR, and the Nur77-dependent luciferase reporter gene were subcloned into plasmid pcDNA. The variant sequences of MEF2D (1-514, 1-121, 1-300, 301-514) and the MEF2D (4KR) lysine-to-arginine mutants, at lysine sites K245/K250/K267/K279, had the Flag epitope at their amino termini. All of the above plasmids were constructed in bacterial expression vectors and the constructed clones were verified by sequencing and then transfected with liposome DMRIE-C. ③The impact of p300 on the trans-activation function of Nur77, mediated by MEF2D, was detected by luciferase reporter assays after Nur77-dependent reporter gene was transfected together with MEF2D, p300 or NFATp into Jurkat cells. In vivo acetylation of endogenous MEF2D and whether acetylation of MEF2D was affected by blocking the expression of p300 were detected by immunoprecipitation. The acetylated sites of MEF2D were detected by acetylation assays in vitro. The impacts of both MEF2D acetylation defects on trans-activation of Nur77 and on apoptosis of T cells induced by Nur77 were detected by luciferase reporter assays and flow cytometry, respectively. RESULTS: ①Although the dimeric complex of MEF2D and NFATp could not induce the transcription of Nur77, significant transcription was achieved with the ternary complex of p300, NFAT and MEF2D. The dimeric complex of p300 and MEF2D could also significantly induce Nur77transcription.②MEF2D was acetylated after the calcium signaling pathway was activated by PMA/Iono. The acetylation level of MEF2D was markedly reduced when p300 expression was blocked by p300 RNAi. ③The simultaneous mutation of K245/K250/K267/K279 lysine sites largely prevented the acetylation of MEF2D, which demonstrated that K245/K250/K267/K279 lysine sites in vitro were the major sites of MEF2D acetylation. ④The MEF2D acetylation defect increased by 2.48 fold the transcription f of Nur77, when compared with vacant vector. But compared with wild type MEF2D, transcription of Nur77 was decreased by 70.4%. ⑤When compared with vacant vector, Nur77 expression could increase total T cell apoptosis of early and late periods from 4.3% up to 16.3%; the co-expression of wild type MEF2D and Nur77 could further increase total T cells apoptosis of early and late periods from 16.3% to 31.0%. However, the co-expression of acetylation defective MEF2D mutant and Nur77 significantly decreased total T cells apoptosis of early and late periods from 16.3% to 9.2%. CONCLUSION : p300 has a major impact on the transactivation function of Nur77 mediated by MEF2D. MEF2D could be acetylated in Nur77-induced T cell apoptosis and acetylated MEF2D could promote T cell apoptosis by upregulating the transcription function of Nur77.

Expression in yeasts and activity of recombinant GST-hunian soluble fibroblast growth factor receptor 1 fusion protein / 中国免疫学杂志

Objective: To express recombinant human soluble fibroblast growth factor receptor 1 ( sFGFR1) and study its antagonistic activity on FGF. Methods: Human sFGFR1 cDNA, isolated from human lung fibroblast cells with RT-PCR was confirmed by DNA sequencing and cloned into pYEX4T-1 yeast expression vector. The recombinant sFGFR1 was expressed in DY150 yeast cells and the product was identified by SDS-PAGE and Western blot. The activity of recombinant sFGFR1 was detected in N1H3T3 proliferation inhibition assay. Results: GSF-sFGFR1 fusion protein was expressed in yeast cells and was observed as a band of 60 Id) on a SDS- PAGE gel and by Western blot. The recombinant fusion protein was also found to be able to suppress FGF-induced proliferation of NIH3Th cells. Conclusion: Recombinant human GST-sFGFR1 fusion protein was expressed in yeast efficiently and showed natural biological activities.