Prognostic significance of tumor-infiltrating CD8⁺ or CD3⁺ T lymphocytes and interleukin-2 expression in radically resected non-small cell lung cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Altered immunoresponse is associated with tumorigenesis and cancer progression. This study assessed the levels of tumor-infiltrating CD3 + or CD8 + T lymphocytes and interleukin-2 (IL-2) protein in radically resected non-small cell lung cancer (NSCLC) tissues to predict overall survival (OS) of the patients.</p><p><b>METHODS</b>Paraffin-embedded tissue specimens from 129 NSCLC patients were retrospectively collected for immunostaining of CD8 + , CD3 + , and IL-2 expression. Clinicopathological and survival data were collected and analyzed using the Chi-squared test, Kaplan-Meier curves, and the log-rank test or the Cox regression model.</p><p><b>RESULTS</b>The data showed a significant inverse association between CD8 + T lymphocyte levels and IL-2 expression (r = -0.927; P = 0.000) and between the levels of CD8 + and CD3 + T lymphocytes (r = -0.722; P = 0.000), but a positive association between CD3 + T lymphocyte levels and IL-2 expression (r = 0.781; P = 0.000) in NSCLC tissues. Furthermore, the levels of CD3 + and CD8 + T lymphocytes and IL-2 expression were associated with tumor stage (P = 0.023, 0.006, and 0.031, respectively) and the level of CD8 + T lymphocytes was associated with the patient gender (P = 0.024). In addition, the levels of CD8 + T lymphocytes were associated with an unfavorable 5-year OS, whereas patients with high levels of CD3 + T lymphocytes in tumor lesions and IL-2-expressing tumors had significantly better 5-year OS rates than patients with low levels.</p><p><b>CONCLUSIONS</b>The levels of CD8 + T cells in tumor lesions and IL-2 expression were both independent predictors of OS for these NSCLC patients. Thus, the detection of tumor-infiltrating CD3 + or CD8 + T lymphocytes and IL-2 expression could be useful to predict the prognosis of radically resected NSCLC patients.</p>

A comparative analysis of the changes of transcriptome after fusion of esophageal cancer cells with human umbilical mesenchymal stem cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To compare the transcriptome of esophageal cancer cells (EC9706), human mesenchymal stem cells (MSCs), and after fusion of esophageal cancer cells with MSCs, and to further study their different expression profiles and the changes of their signaling pathways.</p><p><b>METHODS</b>We examined the gene expression profiles of these cells with transcriptome microarray using LIMMA package and several web-based applications, such as DAVID, ToppGene and MSigDB. The resulting sets of differentially expressed genes (DEGs) were comprehensively analyzed to identify the pathways and their changes after the cell fusion.</p><p><b>RESULTS</b>A total of 4 548 significantly DEGs among the three cell lines were found by LIMMA. Three functional annotation web tools predicted that DNA damage repair, cell cycle arrest and apoptosis pathways were enriched. Total DEGs were mapped to the canonic pathways with KEGGanim which depicted that the core genes of DNA damage repair, cell cycle arrest and pro-apoptosis were up-regulated in fusion cells, and they mightbe combined to respond the fusion-induced damage stress. The up-regulation of suppressive factor DUSP6 might feedback inhibit the MAPK signaling pathway in the fusion cells, too.</p><p><b>CONCLUSIONS</b>Transcriptome analysis suggests that hMSCs and EC9706 cell fusion may inhibit growth of EC cells by induction of pro-apoptotic signaling and DUSP6 negative feedback inhibition mechanism. In addition, the changes of immune regulation-related and differentiation-related genes indicate that the fusion cells inherited certain immune-suppressive function from the stem cells.</p>

The relationship between retinoic acid receptor-β expression and chemotherapy response in esophageal squamous cell carcinoma / 中华内科杂志

Objective To observe the relationship between expression of retinoic acid receptor-β (RAR-β) in esophageal squamous cell carcinoma (ESCC) and chemotherapy response. Methods Fifty-two cases advanced ESCC patients treated by DDP and 5-FU, DDP 80 mg/m2, divided into 5 days;5-FU 375 mg/m2, dl-5. Immunohistochemistry was used to exmine the expression of RAR-β in ESCC. Fifty cases normal esophageal tissue were used as controls. Results RAR-β immunoreactivity was recognizd in both cytoplasm and nucleus, RAR-β positive rate was lower in ESCC compared with normal tissue (61.5%vs 92% ,P ＜0. 05 ). The 52 cases ESCC patients were treated 228 chemotherapy cycles, the overall response rate (OR) was 71.2%. The OR in RAR-β positive patients was 84. 4% (27/32), significant higher than RAR-β negative patients 50. 0% ( 10/20 ) ( P ＜ 0. 05 ). The time-to-progression ( TTP ) for RAR-β positive patients was 5.9 months, the median survival period was 12. 1 months, 2 years survival rate was 56. 7%;whereas TTP for RAR-β negative patients was 2. 1 months, the median survival period was 5.8 months,2 years survival rate was 32. 9%. There was signifcant difference between the 2 groups ( P ＜ 0. 05 ) .Conclusion RAR-β protein expression by immunohistochemistry may be a useful indicator to predict the chemotherapy response and clinical outcome for ESCC, meanwhile it may be an avenue for target therapy.

Depletion of ECRG2 disrupts the spindle assembly checkpoint / 肿瘤研究与临床

Objective To investigate the role of ECRG2,a novel tumor suppressor gene,in spindle assembly checkpoint. Methods Using siRNA approach to deplete the expression of ECRG2, using immunofluorescence to test the distribution of ECRG2,using Western blotting to examine the expression cell cycle proteins.Results ECRG2 localized to centrosomes during interphase and kinetochores during mitosis.Further analysis revealed that ECRG2 participates in the spindle assembly checkpoint.Depletion of ECRG2 abolished the spindle assembly checkpoint.Conclusion Our results indicated that ECRG2 is important for ensuring spindle assembly checkpoint,accurate chromosome segregation,and its depletion may contribute to chmmosome instability and aneuploidy in human cancers.

Exposure level of total N-nitroso compounds in residents of high-and low-risk areas for esophageal cancer in southern / 中华预防医学杂志

<p><b>OBJECTIVE</b>To assess the exposure level of total N-nitroso compounds (TNOCs) in the residents of high- and low-risk areas for esophageal cancer in southern China.</p><p><b>METHODS</b>Samples of duplicate plate diets and 12 hr overnight urine were collected from 120 male adults in each of the 2 areas, a high-risk area (Nanao county) and a low-risk area (Lufeng county) for esophageal cancer. The 240 male healthy subjects (35 - 64 years old) were selected by a 3-stage random cluster sampling procedure. Levels of TNOC, N-nitrosamino acids (NAAs) and volatile N-nitroso compounds (VNOC) in the samples were measured by Thermo Energy Analyzer.</p><p><b>RESULTS</b>The detectable rate (95%) of diet TNOC, daily dietary TNOC intake (4.25 +/- 0.84) micromol/day, 12-hr urinary TNOC excretion levels (1.76 +/- 0.23 ng/12 h) and daily dietary intake of VNOC (266 +/- 31.2 microg/day) in the high-risk area were all significantly higher than those of the low-risk area. Oesophageal cancer mortality rates were positively and significantly associated with daily dietary TNOC intake and 12-hr urinary TNOC excretion. Urinary NAAs excretion levels were not different in the two areas.</p><p><b>CONCLUSION</b>The results suggest that TNOCs may be implicated in the etiology of esophageal cancer in southern China.</p>

Contamination with minimal residual disease in autologous peripheral stem cell collected from Non-Hodgkin's lymphoma patients treated with high-dose therapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To detect the contaminating minimal residual disease (MRD) in autologous peripheral blood stem cells (APBSC) and evaluate its impact on the prognosis of non-Hodgkin's lymphoma NHL patients.</p><p><b>METHODS</b>Minimal residual disease was detected in 72 APBSC samples from 33 NHL patients through PCR or PCR combined with DNA single-strand conformation polymorphism analysis (SSCP) with the BCL-2/IgH, clonal rearrangement of IgH and TCR gamma gene as markers. Minimal residual disease was also monitored in bone marrow samples collected pre-, post-induction chemotherapy and post-transplantation.</p><p><b>RESULTS</b>MRD was positive in 17/72 (23.6%) APBSC samples. The incidence of positive MRD in bone marrow pre-, post-induction chemotherapy and post-transplantation was 44.0% (11/25), 28.1% (9/32) and 11.5% (3/26) respectively. Six (66.6%) of 9 patients with positive MRD in pre-mobilization bone marrow, compared with 2 (8.7%) of 23 patients with negative MRD in bone marrow, were positive in contamination (P < 0.01). The estimated overall 3-year post-transplantation survival rate for patients with positive and negative MRD in their APBSC would be 71.4% and 71.2% respectively, and the estimated 3-year disease free survival rates of 25.0% and 61.5% respectively (P = 0.53).</p><p><b>CONCLUSION</b>APBSC collected from NHL patients after mobilization by chemotherapy combined with colony stimulating factor may be contaminated by lymphoma cells. The presence of minimal residual disease in bone marrow at mobilization may increase the incidence of APBSC contamination.</p>

Search for interacting proteins of esophageal cancer related gene-1 encoded protein through the yeast two-hybrid system / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To understand the role that esophageal cancer related gene-1 (ECRG-1) plays and to search for ECRG-1-interacting proteins.</p><p><b>METHODS</b>A DNA fragment encoding the carboxy-terminus of ECRG-1 (amino acids 40 - 418) was inserted into pGBKT7-DNA-BD vector and fused in-frame to the DNA-binding domain of GAL4. Then, it was used as a bait to screen the human fetal liver cDNA library by yeast two-hybrid, with the cDNA fragment inserted into pACT2 vector and fused in-frame to the Gal4 activation domain. If ECRG-1 interacted with a protein encoded by a cDNA fragmant in the yeast, the transcription of reporter Gene could be activated. With the false positive clonies eliminated, the inserts in the positive plasmids were sequenced and compared to those in the GenBank.</p><p><b>RESULTS</b>In approximately 3 x 10(6) independent tansformants screened, 23 clonies exhibited the expression of reporter gene. After eliminating the false positive clonies, two cDNA fragments were obtained. DNA sequencing revealed that one encoded Miz-1 (Myc-interacting Zn finger protein-1), and another encoded FLNA (actin-binding protein-280), Miz-1, being a Zn finger protein, could be bound to p15 promotor and activated the transcription. FLNA, being an actin-binding protein took part in the TGF-beta pathway via interaction with Smad.</p><p><b>CONCLUSION</b>ECRG-1 is able to be specifically bound to Miz-1 and FLNA in the yeast. It may play a role in the regulation of cell cycle via interaction with Miz-1 and FLNA.</p>

Studies on the activation of oncogenes by alternariol in human fetal esophageal epithelium / 中国病理生理杂志

This paper reported that the activation of oncogenes in human fetal esopha geal epithelium treated by alternariol (AOH). It was found that NIH/3T3 cells were transformed via transfeetion of DNA extracted from human fetal esophageal epithelium which was cultured and treated by 10?g/ml AOH in a short term in vitro. The efficiency of primary loci was 0.17 focus per ?g of DNA. In the secondary transfection, the efficiency was 0.58 focus per ?g of DNA (P

The role of DR5 in TRAIL-induced apoptosis for Jurkat cell line / 中国免疫学杂志

Objective:To study the role of DR5 in TRAIL apoptotic signal transduction. Methods:BALB/C mice were immunized with recombinant DR5 that contains the full-length extracellular domain of the human DR5. Anti-DR5 mAb was generated by hybridoma. The level of DR5 expression on Jurkat cell line was examined by flow cytometry. The rates of TRAIL-induced apoptosis and anti-DR5 mAb blocking on Jurkat cells were tested by flow cytometry with TRAIL apoptosis kit.Results:The percentage of DR5 expression on Jurkat cells was 94 83%. TRAIL and anti-TRAIL mAb could kill Jurkat cells on dose-dependent, and the killing rate was 90% in the concentration of 50～100 ng/ml. The killing role of TRAIL could be blocked on Jurkat cells pretreated with anti-DR5 mAb. The average percentage of blocking was 90 49%.Conclusion:DR5 plays a very key role in TRAIL induced apoptosis in Jurkat cells.