Journal of Practical Oncology

Construction and identification of shRNA lentiviral vectors targeting histone lysine transferase KAT6B gene

JIN Junjie, AN Jing, CAO Difei, SONG Aili, ZHAO Lili, LIU Zhaoliang

2018, 32(1): 1-6. doi:10.11904/j.issn.1002-3070.2018.01.001

Abstract ( 143 )

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Objective The aims of this study were to construct short hairpin RNA(shRNA)lentiviral vector in breast cancer T47D cells,to carry out RNA interference on lysine acetyltransferase 6B(KAT6B/MORF)gene,to down-regulate its expression and to explore its function. Methods Two pairs of single-stranded short hairpin RNA(shRNA5 and shRNA8)and the corresponding control sequences(Scramble5 and Scramble8)were synthesized based on the CDS of KAT6B gene.Polymerase chain reaction(PCR)was used to amplify double-stranded and ligated with the entry vector(pENTR/pSM2(CMV)GFP),which were subjected to a double digestion(EcoRl and Xhol)linearization and homologous recombination with the entry vector(pENTR/pSM₂(CMV)GFP)to obtain an entry clone containing the desired fragment.The target fragment was recombined onto the target vector(pLenti x1 puro DEST)via the LR cloning reaction of the Gateway system.The lentiviral packaging plasmids were co-transfected into HEK-293T cells with two pairs of target plasmids.The supernatant of HEK-293T cells was collected and transformed into T47D cells.The expression of KAT6B protein was detected in T47D cells by Western blot. Results The single colony obtained from the transformation was identified by sequencing,which was consistent with the target sequence,indicating that the lentiviral vector had been successfully constructed.The expression of KAT6B protein was significantly lower in the shRNA KAT6B group than that in the control group,which indicated that the constructed gene silencing vector could play a role in the KAT6B gene in T47D cells. Conclusion The shRNA lentiviral gene silencing vectors of KAT6B were constructed and identified in T47D cells,which indicated that the foundation for further study KAT6B gene plays an inhibitory effect on breast cancer.

Expression,prognosis and function of long chain non-coding RNA-Linc00152 in breast cancer

ZHENG Wei, XU Shouping, PANG Da

2018, 32(1): 7-13. doi:10.11904/j.issn.1002-3070.2018.01.002

Abstract ( 150 )

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Objective The aim of this study was to explore the expression,prognosis and related function of Linc00152 in breast cancer. Methods Thirty-three cases of breast specimens were selected for RNA-Sequencing.The expression of Linc00152 was detected by qPCR in 50 pairs of breast cancer tissues and adjacent tissues.Combined with GEO and TCGA databases,the correlation between Linc00152 expression and the degree of malignancy and the prognosis of patients was analyzed.Cell proliferation,apoptosis and cell migration were detected in breast cancer MDA-MB-231 cell line,gastric cancer SGC-7901 cell line and renal cell carcinoma 786-O cell line. Results Linc00152 was highly expressed in breast cancer(P＜0.001),and was higher in HER2 positive and triple negative breast cancer(P＜0.001).In patients with high expression of Linc00152,the event-free survival and the metastasis-free survival were very poor(P＜0.001,P＜0.01).After knockdown Linc00152,the cell proliferation,migration and invasion were decreased and the apoptosis was increased(P＜0.05). Conclusion Linc00152 has a role of promoting cancer in malignant tumors and may be a potential therapeutic target.

Correlation between single nucleotide polymorphisms of ERα gene and bone loss associated with aromatase inhibitors in postmenopausal women with breast cancer

YIN Yulian, ZHANG Weihong, ZHOU Yue, YE Meina, CHEN Hongfeng

2018, 32(1): 14-18. doi:10.11904/j.issn.1002-3070.2018.01.003

Abstract ( 184 )

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Objective The aim of this study was to explore the correlation between postoperative aromatase inhibitor(AIs)- based bone metabolism and ERα gene rs9340799,rs2234693 single nucleotide polymorphisms(SNPs)in breast cancer. Methods One hundred and sixty-six breast cancer patients who underwent AIs treatment(≤2 years)were enrolled and hospitalized in our hospital from October 2015 to April 2017.The ERα gene rs9340799 and rs2234693 sites were sequenced and compared subtype of lumbar spine and femur,bone mineral density BMD value and the relationship between BMD value and T value. Results The BMD of lumbar spine in patients with ERα gene rs9340799 was significantly different when compared to those of A/A,A/G and G/G(P＜0.01).The BMD of lumbar spine in patients with A/A and A/G genotypes were significantly higher than those in G/G genotypes(P＜0.05).The BMD of lumbar spine in patients with ERα gene rs2234693 was significantly different when compared to those of T/T,T/C and C/C(P＜0.01).The BMD of lumbar spine in patients with T/T and C/T genotypes were significantly higher than those in C/C genotypes(P＜0.05).However,there was no difference in femoral BMD,lumbar spine,and femur T between the 2 subtypes of patients with genotypes(P＞0.05). Conclusion Aromatase inhibitor-related bone loss(AIBL)may be related to ERα gene phenotype.In ERα gene rs9340799 and rs2234693 loci,C and G alleles may be susceptible genes for aromatase inhibitor-related bone loss(AIBL).

Correlation between the decline of severe granulocyte in the early stage of chemotherapy and the prognosis of small cell lung cancer

YANG Wenjuan, YU Jing, HUANG Zhao, ZHANG Junhong, XIE Conghua

2018, 32(1): 19-24. doi:10.11904/j.issn.1002-3070.2018.01.004

Abstract ( 176 )

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Objective The aims of this study were to investigate the correlation between the early stage of severe granulocytopenia and the curative effect on clinical prognosis of chemotherapy in the first-line EP regimen of small cell lung cancer(SCLC). Methods A retrospective study analysis of 82 cases of first-line EP chemotherapy in patients with SCLC was collected clinical data,according to the time of patients with severe neutropenia.Patients were divided into two groups i.e.early-onset group(the first two cycles appeared Ⅲ-Ⅳ neutrophil decline)and non-early-onset group(Ⅲ~Ⅳ neutropenia did not appear or three cycles and later).The main indicators for the observation were objective response rate(ORR),disease control rate(DCR),time to progression(TTP)and overall survival(OS).Kaplan-Meier method and Log-rank test were used to analyze univariate survival and Cox proportional hazards model to analyze multivariate survival. Results The effective rates of chemotherapy were 81.8% and 75.5%(P=0.499),and DCRs were 97.0% and 95.9% in early-onset and non-early-onset groups,respectively(P＞0.05).The median survival time was 10.4 months and 6.9 months in early-onset and non-early-onset groups,respectively(P=0.001).The median OSs were 22.4 months and 16.0 months in early-onset and non-early-onset groups,respectively(P=0.023).Multivariate survival analysis revealed that smoking index,number of chemotherapy cycles,chest radiotherapy and early-onset severe neutropenia were independent prognostic factors for SCLC(P＜0.05). Conclusion Chemotherapy-related loss of early severe neutropenia correlates with the efficacy of chemotherapy in SCLC and is an independent predictor of prognosis in SCLC.

Effect of systemic inflammation response index on clinical prognosis of patients with glioma and its relationship with IDH1 mutation

ZHANG Lizhi, LIU Ping, JI Huijun, LI Shouchun, ZHANG Zhiwen

2018, 32(1): 25-32. doi:10.11904/j.issn.1002-3070.2018.01.005

Abstract ( 150 )

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Objective The objective of this study was to investigate the effect of systemic inflammation response index(SIRI)on clinical prognosis of patients with glioma and its relationship with dehydrogenase 1(IDH1)mutation. Methods Eighty patients with glioma who underwent surgery in the department of Neurosurgery were collected from August 2006 to November 2015.The best clinical cutoff value for SIRI was determined using operating characteristic curve(ROC)and grouped accordingly.The Kaplan-Meier and log-rank methods were used to analyze the postoperative survival of the two groups of patients.The independent clinical prognostic factors were evaluated by Cox′s proportional hazards regression model.The IDH1 mutation was detected by immunohistochemistry and DNA sequencing. Results SIRI was an independent prognostic factor of glioma,and the best clinical cutoff value was 0.67 ×10⁹/L.The median progress free survival(PFS)and overall survival(OS)of patients with low SIRI group were 46.90 months and 57.90 months,and the median PFS and OS of patients with high SIRI group were 31.78 months and 47.22 months,respectively.There was significant difference between the two groups in the median survival time of PFS and OS by log-rank method(P＜0.05).Univariate and multivariate analysis showed that age,gender,type of surgery,WHO stage,SIRI and IDH1 mutation were the independent prognostic factors in neurostein stromal tumors.Patients with low-grade SIRI and glioma with IDH1 mutation have a better prognosis than other conditions. Conclusion SIRI is an independent prognostic factor of glioma.It is simple,convenient and reproducible,and may be used to predict the prognosis of patients with glioma.

Clinical effect of flurbiprofen axetil in the postoperative analgesia of cervical cancer surgery

WANG Qinghui, SUN Yue, JIANG Wanwei

2018, 32(1): 33-37. doi:10.11904/j.issn.1002-3070.2018.01.006

Abstract ( 147 )

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Objective The objective of this study was to investigate the analgesic effect of flurbiprofen axetil and its effect on immune factors after cervical cancer surgery. Methods Ninety patients with cervical cancer undergoing laparoscopic surgery were randomly divided into three groups with 30 patients in each group in Zhongshan Hospital Affiliated to Dalian University from January 2016 to June 2017.The indexes of assessment were visual assessment of visual analog scale(VAS)pain assessment and postoperative adverse reaction at 2,12,24 and 48 h after operation.The levels of CD4,CD8,IL-1,IL-6,CD4/CD8 and PGEs in the serum at 12,24 and 48 h after operation were measured. Results The VAS scores in the A group were significantly lower than those in the B and C groups during 12 and 24 h after operation(P＜0.05).But there were no significant differences in the levels of CD4,CD8,IL-1,IL-6,CD4/CD8 and PGEs amongst the three groups(P＞0.05).The levels of IL-1 and IL-6 at 2,12 and 24 h after operation were significantly higher than those in the baseline(P＜0.05).However,the levels of IL-1 and IL-6 in the C group was significantly higher than those in the A and B groups(P＜0.05).Compared to before operation,the ratio of CD4/CD8 was decreased and the level of PGE2 was increased in the three groups after operation.After 24 h operation,the ratio of CD4/CD8 in the B group were significantly lower than that in the C group(P＜0.05).The level of PGE2 at 12 h after operation was significantly increased in the B and C groups(P＜0.05). Conclusion The combination of flurbiprofen axetil and sufentanil in the laparoscopic surgery of cervical cancer can improve postoperative analgesia and reduce adverse reactions,effectively reduce the secretion of inflammatory mediators and minor affect on cellular immune function.

Research progress of PERK signaling pathway under endoplasmic reticulum stress in tumor

OUYANG Zhongrui, CHAI Shuang, ZHAO Haiqi, LIU Yaohua

2018, 32(1): 38-41. doi:10.11904/j.issn.1002-3070.2018.01.007

Abstract ( 127 )

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During growth,invasion and metastasis,tumor cells undergo endoplasmic reticulum stress(ERS)under hypoxia,hypoglycemia and other environmental stresses.In response to ERS,tumor cells induce unfolded protein response(UPR).PERK signaling pathway as a key pathway to activate UPR can promote survival,proliferation,invasion and protection of tumor cells by increasing tumor tolerance to adverse microenvironment,inducting angiogenesis,inducing autophagosome formation and activating apoptotic signal molecules.Tumor cells are induced apoptotic and autophagic death when UPR reaches a certain extent.

Research progress on the relationship between microRNA-196a and tumor

XIN He, WANG Chuanzhuo, LIU Zhaoyu

2018, 32(1): 42-46. doi:10.11904/j.issn.1002-3070.2018.01.008

Abstract ( 156 )

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As a member of the miRNA family, microRNA-196a (miR-196a) has received much attention in recent years. MiR-196a not only plays an important regulatory role in various biological processes, but it also shows that miR-196a also functions as oncogene in the tumorigenesis and progression. In recent studies, miR-196a is high expression in the serum, tissues and cells of patients with cancer, and can promote tumor cell proliferation, invasion and metastasis, inhibit tumor cell apoptosis and enhance tumor drug resistance. In this paper, we reviewed the research progress on the correlation between miR-196a and tumor based on the latest reports at domestics and abroad.

Regulative mechanism of long non-coding RNA in gastric cancer and its role in traditional Chinese medicine

YU Jiahui, LIU Xuan, LI Qi, LU Ye, YUE Xiaoqiang

2018, 32(1): 47-52. doi:10.11904/j.issn.1002-3070.2018.01.009

Abstract ( 144 )

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Long non-coding RNA(LncRNA)is a class of RNA that cannot encode translated proteins with more than 200 nucleotides in length.It can be involved in the regulation of X chromosome silencing,chromatin modification,transcriptional activation,transcriptional interference and other regulatory processes by binding to DNA,RNA or proteins.In recent years,more and more studies have confirmed that LncRNA plays an important role in the occurrence,development,invasion and metastasis of gastric cancer.At the same time,many studies have demonstrated LncRNA as the target of traditional Chinese medicine for the development and progression of anti-gastric cancer.This review introduces the mechanism of LncRNA in the development and progression of gastric cancer,and as a target for traditional Chinese medicine treatment prospects.

Stereotactic radiotherapy for early stage of non - small cell lung cancer

SUN Mingliang, XU Jianyu, XU Xiangying

2018, 32(1): 53-56. doi:10.11904/j.issn.1002-3070.2018.01.010

Abstract ( 155 )

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At present,approximately 20% of patients with clinically diagnosed early non-small cell lung cancer(NSCLC)are inoperable for their own reasons.Stereotactic radiotherapy(SRT)has the advantages of short treatment time,mild treatment-related injury and high local control rate.Currently,it has been used internationally as a first-line treatment for early incapacity of NSCLC.SRT has also achieved encouraging therapeutic effects in the treatment of early-stage NSCLC,but there are also some problems to be solved urgently.This article aims to summarize the dosimetry,clinical indications and radiotherapy injury of SRT in the treatment of early-stage NSCLC.

Research progress in miRNA regulatory immune checkpoint in cancer therapy

MIAO Suping, GUO Erliang, PEI Rong, JIANG Huanyu, MIAO Susheng

2018, 32(1): 57-62. doi:10.11904/j.issn.1002-3070.2018.01.011

Abstract ( 147 )

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One of the main mechanisms of tumorigenesis and development is silencing of the patient's immune response to cancer-specific antigens.The defect of cancer immune surveillance may occur at any stage of tumor progression.In the tumor microenvironment,the abnormal expression of the immune checkpoint molecules that have an activation or inhibition effect on T lymphocytes can cause immune tolerance or escape of tumor cells.Targeted immune checkpoint molecules such as PD-1(programmed cell death protein 1)and its ligand PD-L1,have been shown to be new directions for the treatment of many types of cancer.microRNAs(miRNAs)play an important role in tumor microenvironment.Studies have shown that miRNAs are highly expressed in some tumors and play an important role in immune response,especially in early regulation.Therefore,miRNAs may be ideal candidates for the regulation of immune checkpoints in cancer therapy.The abnormal expression of multiple miRNAs in cancer cells provides new opportunities for cancer therapy,but the exact function of these miRNAs and their interaction with immune checkpoints are still in the exploratory phase.This review summarizes the recent findings regarding the use of miRNAs as molecular regulators of immune checkpoints and their potential applications in the treatment of cancer in clinical practice.

Research progress of imaging evaluation of neoadjuvant chemotherapy in breast cancer

LI Yujiao, SHANG Naijian

2018, 32(1): 63-67. doi:10.11904/j.issn.1002-3070.2018.01.012

Abstract ( 128 )

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Traditionally,conventional imaging modalities used to assess neoplasms for neoadjuvant chemotherapy responses have their own limitations.Functional imaging can predict neoadjuvant chemotherapeutic responses early and thus guide personalized therapies.However,there is no standard method of imaging assessment for neoadjuvant chemotherapy follow-up.The aim of this article is to discuss the accuracy,advantages,limitations,and future directions of various imaging methods,especially functional imaging,for evaluating the response to chemotherapy in patients with breast neoadjuvant chemotherapy.

Current status:low dose spiral CT lung screening and pulmonary nodules

KONG Weijia, AN Tian, LV Bo, JIANG Guangjian

2018, 32(1): 68-72. doi:10.11904/j.issn.1002-3070.2018.01.013

Abstract ( 134 )

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Lung cancer has become one of the most threatening malignant tumors in human life.Its morbidity and mortality rank is the first place in malignant tumors,so it is particularly important to screen for lung cancer.With the widespread use of low-dose CT,the detection rate of pulmonary nodules is increasing,and its research is also in-depth.This article described the status of lung cancer screening,factors of benign and malignant pulmonary nodules.It could provide the basis information for prevention and treatment of the lung cancer and pulmonary nodules.

Regulation of long non-coding RNAs in the tumor microenvironment

SHEN Meiying, PANG Da

2018, 32(1): 73-76. doi:10.11904/j.issn.1002-3070.2018.01.014

Abstract ( 136 )

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Long non-coding RNAs(LncRNAs),a class of RNAs,are more than 200 nucleotides in length and do not encode protein.The abnormal expression of LncRNAs is closely associated with the occurrence and development of various human diseases.In recent studies,LncRNAs regulate the tumor immune response by regulating the differentiation and function of tumor-related immune cells.In addition,LncRNAs affect the microenvironment by regulating the expression of multiple inflammatory factors.This review will summarize that LncRNAs regulate the tumor microenvironment.

Research progress of photodynamic therapy in malignant tumor of digestive tract

LI Hongwei, LIU Chuan, WANG Lang, LIU Jun, YANG Hanfeng, DU Yong

2018, 32(1): 77-81. doi:10.11904/j.issn.1002-3070.2018.01.015

Abstract ( 136 )

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Photodynamic therapy(PDT)is a new type of minimally invasive treatment in recent years.After the photosensitizer is injected into the body for a period of time,it specifically accumulates in the tumor tissue.At this time,the tumor tissue site is irradiated with light of a specific wavelength and the photosensitizer occurs photodynamic reaction to kill tumor cells.With the continuous progress of endoscopic guidance technology and the emergence of new photosensitizers,PDT has made significant progress in the treatment of gastrointestinal malignancies and the curative effect is remarkable.This article describes the principle of PDT,and focuses on the application of PDT in gastrointestinal cancer for clinical treatment and research as a reference.

Research progress of intercellular adhesion molecule-1 in tumor

ZHUANG Minmin, ZHANG Yunyan

2018, 32(1): 82-86. doi:10.11904/j.issn.1002-3070.2018.01.016

Abstract ( 165 )

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Intercellular adhesion molecule(ICAM-1),also known as CD54,is a transmembrane glycoprotein of the immunoglobulin superfamily and involved in tumor cell immune regulation,angiogenesis,invasion and distant metastasis.Many studies from domestic and abroad have proved that ICAM-1 is highly expressed in a variety of malignant tumors,which promotes the occurrence,development and prognosis of tumor.ICAM-1 also plays an important role in predicting the chemosensitivity of individual tumors.Therefore,ICAM-1 may provide a reference for the diagnosis and treatment of malignant tumors.This article summarizes effects of ICAM-1 on malignant tumors in recent years.

Research progress of estrogen receptor-related receptor γ in tumors

WANG Xiaoxiao, HUA Teng, WANG Hongbo

2018, 32(1): 87-91. doi:10.11904/j.issn.1002-3070.2018.01.017

Abstract ( 145 )

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Estrogen receptor-related receptor γ(ERR γ)belongs to the orphan nuclear receptor family(NRs),which can regulate the expression of multiple genes in the absence of natural ligands and play an important role in maintaining the basic biological activities of cells.In recent years,the data from many studies have shown that ERR γ is involved in the development and progression of tumor,including tumor cell metabolism,proliferation,metastasis and angiogenesis.Besides,the effect of ERR γ on tumor progression and prognosis has the specificity of cell and tissue.This paper will review the clinical significance of ERR γ and its mechanism in metabolism and tumors related estrogen ,which provided the theoretical basis for metabolism and estrogen-related tumorigenesis and targeted therapy.

Progress of Raman spectroscopy in cancer diagnosis of human organization

ZHAO Qianyu, SUN Yihua

2018, 32(1): 92-96. doi:10.11904/j.issn.1002-3070.2018.01.018

Abstract ( 142 )

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Cancer is one of the causes of higher human mortality,despite the continuous improvement of medical technology,Raman spectroscopy is a non-destructive testing which has unique advantages over the detection speed and high sensitivity,moreover it is expected to become a new model of early diagnosis of clinical cancer.This paper reviews the recent progress of domestic and foreign scholars using Raman spectroscopy to study human cancerous tissue,including gastric cancer,oral squamous cell carcinoma,cervical cancer,nasopharyngeal carcinoma,breast cancer and colorectal cancer.

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