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Chinese Journal of Clinical Oncology

1963  to  Present  ISSN: 1000-8179

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Advances in the treatment of patients with stageⅡ-ⅢA non-small cell lung cancer and the EGFR mutation

Yong TANG ; Guibin QIAO

Chinese Journal of Clinical Oncology.2019;46(14):707-711. doi:10.3969/j.issn.1000-8179.2019.14.812

The incidence of non-small cell lung cancer (NSCLC) is the highest among malignant tumors. StagesⅡtoⅢA patients are potentially treatable. Perioperative chemotherapy is the standard treatment for NSCLC; however, in patients with the EGFR mutation, neoadjuvant or adjuvant targeted therapy can improve disease-free survival (DFS). Despite this, the survival benefit is not clear. Postop-erative adjuvant radiotherapy can enhance survival in patients with stageⅢA (N2) NSCLC. Durvalumab maintenance therapy, after concurrent chemoradiotherapy, has become the new standard for patients with locally advanced and unresectable NSCLC. Immuno-therapy requires additional investigation in patients with driver gene mutations, as does the combination of immunotherapy plus che-motherapy. Notably, anti-angiogenesis therapy has failed as a postoperative adjuvant therapy.

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Expression and function of lncRNA BDNF-AS in breast cancer

Duoming WU ; Li WU ; Xiaobin ZHANG

Chinese Journal of Clinical Oncology.2019;46(14):712-717. doi:10.3969/j.issn.1000-8179.2019.14.931

Objective: To determine expression of brain-derived neurotrophic factor antisense (BDNF-AS) long non-coding RNA (ln-cRNA) in breast cancer, and to investigate its effects on proliferation, apoptosis, migration and invasion. Methods: Between 2016 and 2018, samples from 88 cases of breast cancer were collected at the First Hospital of Lanzhou University. RT-qPCR was used to deter-mine expression of lncRNA BDNF-AS in breast cancer tissue and cells. A pcDNA3.1 plasmid was used to overexpress BDNF-AS in MDA-MB-231 cells. Cell viability was quantified using an MTT assay, proliferative capacity was determined using an EdU assay and a colori-metric assay was used to measure the Caspase-3 activity. Moreover, the protein levels of Bax, Bcl-2, MMP-9, E-cadherin, and BDNF were quantified by Western blot. Scratch and transwell assays were used to determine cell migration and invasion. Results: Lower ln-cRNA BDNF-AS expression was observed in breast cancer tissue and cells compared with normal paracancerous tissues (P<0.05), and with normal, HBL-100 breast cells (P<0.01). BDNF-AS expression negatively correlated with tumor-node-metastasis (TNM) stage (P<0.05) and lymphatic metastasis (P<0.05) of breast cancer. Overexpression of BDNF-AS with the pcDNA3.1 plasmid decreased viability of MDA-MB-231 cells (P<0.01), EdU-positive cells (P<0.01), and Caspase-3 activity (P<0.01). Additionally, Bcl-2, MMP-9, and BDNF ex-pression was downregulated (P<0.01), while Bax and E-cadherin expression was upregulated (P<0.01). Overexpression of BDNF-AS al-so inhibited cell healing and invasion which were determined by scratch assays (P<0.01). Conclusions: LncRNA BDNF-AS expression is downregulated in breast cancer, which inhibits breast cancer cell proliferation, migration, invasion, and promotes apoptosis.

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Expression and mechanism of microRNA-613 in breast cancer

Kepeng ZHU ; Xunrong XIAO ; Yi LUO ; Wen YI ; Junming YIN ; Chuan YANG ; Guocheng DU

Chinese Journal of Clinical Oncology.2019;46(14):718-722. doi:10.3969/j.issn.1000-8179.2019.14.676

ABSTRACT Objective: To investigate the expression and mechanism of microRNA (miRNA)-613 in breast cancer. Methods: A total of 91 specimens of breast cancer tissue were collected from Nanchong Central Hospital between May 2017 and May 2018. Quantitative real-time PCR (qRT-PCR) was used to estimate miRNA-613 expression levels in breast cancer and adjacent tissues and breast cancer ( cells MDA-MB-231, MDA-MB-468, and MCF-7) and normal breast epithelial (HBL-100) cell lines. Based on these data, the relationship between miRNA-613 expression and clinicopathological characteristics and prognosis in breast cancer patients were analyzed using the cancer genome atlas (TCGA) database. A dual-luciferase reporter assay was used to detect the binding of miRNA-613 to the 3'UTR of SOX9. Effects on cell proliferation and cell invasion and migration upon transfection of MDA-MB-231 cells with miRNA-613 mimics were detected by the CCK-8 assay and Transwell invasion and migration assays, respectively. In addition, Western blot was used to estimate the expression levels of SOX9, β-catenin, E-cadherin, and Vimentin in the transfected cells. Results: The expression of miRNA-613 in breast cancer tissues was significantly lower than that in adjacent tissues (P<0.05) and was found to be closely related to TNM stage and lymph node metastasis (P<0.05). TCGA survival data showed that miRNA-613 expression was not related to the overall survival rate of breast cancer patients (P>0.05 ). The expression of miRNA-613 in breast cancer cell lines was significantly lower than that in the normal breast epithelial cell line (P<0.05). Similarly, the expression of miRNA-613 in highly invasive metastatic breast cancer cell lines (MDA-MB-231 and MDA-MB-468) was significantly lower than that in the metastatic breast cancer cell line MCF-7 with lower invasion ability (P<0.05). The dual-luciferase reporter assay showed that miRNA-613 could specifically bind to the 3'UTR of SOX9. Upregulation of miRNA-613 expression could inhibit the proliferation, invasion, and migration of MDA-MB-231 cells (P<0.05). This was associated with the downregulated expression of SOX9, β-catenin, and Vimentin (P<0.05) and upregulation of E-Cadherin expression (P<0.05). Conclusions: The expression of miRNA-613 was decreased in breast cancer tissues and cell lines. MiRNA-613 may inhibit the proliferation, invasion, and metastasis of breast cancer cells and epithelial-mesenchymal transition by regulating the SOX9 and Wnt/β-catenin signaling pathways.

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Expression and potential role of ajuba LIM protein in oral squamous cell carcinoma

Xiaofeng YAO ; Rui JIN ; Yingjie TAO ; Wenyu GUO

Chinese Journal of Clinical Oncology.2019;46(14):723-727. doi:10.3969/j.issn.1000-8179.2019.14.512

Objective: To assess the expression of ajuba LIM protein (AJUBA) in oral squamous cell carcinoma (OSCC) and to determine its role in cell proliferation, migration, and invasion in OSCC. Methods: The expression of AJUBA at mRNA and protein levels in OSCC was determined by quantitative polymerase chain reaction (qPCR) and immunohistochemical approaches, respectively. This was fol-lowed by analysis of the correlations between AJUBA levels and clinicopathological features of OSCC. The effects of AJUBA on cell pro-liferation, migration, and invasion in OSCC were assessed by MTT, wound healing, and transwell migration assays, respectively. West-ern blot assays were performed to check for the potential regulation of the Snail/E-cadherin pathway by AJUBA. Results: The expres-sion of AJUBA was significantly higher in OSCC tissues compared to that in adjacent normal tissues and correlated with T stage, cell dif-ferentiation, lymph node metastasis, and recurrence in OSCC. Elevated AJUBA levels indicated poor prognosis in patients with OSCC. Depletion of AJUBA impaired cell proliferation, migration, and invasion abilities of OSCC cells. Data from Western blot assays showed that AJUBA facilitated the expression of Snail but inhibited that of E-cadherin. Conclusions: AJUBA is overexpressed in OSCC and may influence cell proliferation and invasion in OSCC by modulating the Snail/E-cadherin pathway.

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Clinicopathological characteristics and prognostic factors of 83 patients with ovarian metastasis from gastric cancer

Shaoqing LI ; Hongqing XI ; Jiyang LI ; Kecheng ZHANG ; Zhi QIAO ; Bo WEI ; Lin CHEN

Chinese Journal of Clinical Oncology.2019;46(14):728-733. doi:10.3969/j.issn.1000-8179.2019.14.789

Objective: To explore the clinicopathological characteristics and prognostic factors of patients with ovarian metastasis from gastric cancer. Methods: We retrospectively analyzed the clinical data and treatment strategies of 83 patients with metastatic ovarian tumors treated at PLA General Hospital between January 2006 and December 2017. Univariate analysis using the Log-rank test and multivariate analysis using the Cox proportional-hazards model were used to identify the prognostic factors. Results: The median diam-eter of the metastatic ovarian tumors was 7.1 (1.0-24.0) cm. Of these patients, 36 (43.4%) had unilateral metastasis and 47 (56.6%) had bilateral metastasis; 35 (42.2%) patients had peritoneal metastasis. All patients received chemotherapy, including 57 (68.7%) pa-tients who underwent combined-modality resection of the metastatic tumors and 22 patients (26.5%) who received hyperthermic in-traperitoneal chemotherapy. Of these patients, 74 (89.1%) were followed up, with a median survival time of 15 [95% confidence inter-val (CI): 12.5-17.5] months. The 1-year, 3-year, and 5-year overall survival rates were 71.1%, 6.5%, and 0, respectively. Univariate analy-sis showed that risk factors including≥6 metastatic lymph nodes, metastasectomy, synchronous ovarian metastasis, peritoneal carcino-matosis, estrogen receptor (ER) positivity, and high levels of serum carcinoembryonic antigen and cancer antigen-125 (CA125) might af-fect the prognosis (P<0.05). Multivariate analysis showed that metastasectomy, synchronous ovarian metastasis, combined peritoneal carcinomatosis, and ER positivity were independent factors affecting prognosis (P<0.05). Conclusions: We found that the presence of synchronous ovarian metastasis or combined peritoneal carcinomatosis indicated a poor prognosis; in contrast, ER-positivity predicted a better prognosis than ER-negativity. Metastasectomy may prolong the survival of patients.

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A combination of lenalidomide, bortezomib, and dexamethasone (RVD) provides deep-er responses in patients with newly diagnosed multiple myeloma

Jing JIA ; Aijun LIU ; Wenming CHEN ; Yin WU ; Yanchen LI ; Yun LENG ; Wen GAO

Chinese Journal of Clinical Oncology.2019;46(14):734-738. doi:10.3969/j.issn.1000-8179.2019.14.994

Objective: This study investigated the efficacy and safety of a combination of lenalidomide, bortezomib, and dexametha-sone (RVD) in patients with newly diagnosed multiple myeloma (NDMM). Methods: The clinical features and responses of 48 patients with NDMM who were treated with RVD from January 2015 to May 2019 in Beijing Chaoyang Hospital were retrospectively analyzed. Results: The median age of the 48 patients was 59 years (range: 34-79). Among these, 44 patients were Durie-Salmon stageⅢ, 15 were ISS stageⅡ, 19 were ISS stageⅢ, and 12 had plasmacytoma; 32.5% of all patients were cytogenetic high-risk. All patients re-ceived a median of four cycles (range: 1-9) of the RVD regimen as induction treatment. The overall response rate was 97.9%, with 35.4% of patients achieving complete response (CR) or better. The rate of very good partial remission (VGPR) or better was increased from 64.1% (after two cycles) to 84.6% (after four cycles). The mean collection of CD34+cells was 4.2 (± 2.6)×106/kg. Negative minimal residual disease (MRD), as indicated by next-generation flow (NGF), was achieved in 20.6% of patients after induction. Two patients with positive MRD after induction became MRD negative after transplantation. Two patients developed grade 3 or 4 hematologic toxic-ity. No nonhematologic toxicity of grade 3 or 4 was observed. Conclusions: In patients with NDMM, RVD treatment resulted in signifi-cantly improved response rates and exhibited an acceptable risk-benefit profile, with no adverse impact on stem cell collection. RVD combined with transplantation significantly improved the negative rate of MRD, as indicated by NGF.

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Efficacy and safety of PEG-rhG-CSF therapy in the primary and secondary prevention of chemotherapy-induced neutropenia

Huiping LI ; Zhengfu FAN ; Hong ZHENG ; Yunong GAO ; Meifeng TU ; Guohong SONG ; Bing SHAO ; Tian GAO ; Jun ZHU

Chinese Journal of Clinical Oncology.2019;46(14):739-744. doi:10.3969/j.issn.1000-8179.2019.14.967

Objective: To evaluate the efficacy and safety of PEG-rhG-CSF therapy in the primary and secondary prevention of chemo-therapy-induced neutropenia . Methods: This single-center, one-arm, and open-label clinical study involved 217 patients with non-my-eloid malignant tumors. These patients included 18 gynecologic oncology (3 endometrial and 15 ovarian cancer), 50 breast cancer, 30 bone tumor, and 119 lymphoma patients who underwent a total of 774 cycles of chemotherapy, comprising 146 primary and 71 sec-ondary prevention patients. The patients ≥45 kg and those <45 kg received a single subcutaneous injection of 6 mg and 3 mg PEG-rhG-CSF, respectively, 24-48 h after the chemotherapy was completed. All patients received only one dose of PEG-rhG-CSF admin-istration per chemotherapy cycle. Results: The overall incidence of febrile neutropenia (FN) was found to be 5.7%, with rates of 4.9% and 7.2% in the primary and secondary prevention groups, respectively. Univariate and multivariate Logistic regression analyses re-vealed that the longer PEG-rhG-CSF was sustained in the treatment cycle, the lower the incidence of FN was. The incidence of FN was significantly lower in the second cycle of the treatment than in the first in both the primary and secondary prevention groups (cycle 1 vs. cycle 2: 11.6% vs. 4.4%, respectively, P=0.039, in the primary group; 16.9% vs. 5.6%, respectively, P=0.034, in the secondary group). The overall incidence of gradeⅣneutropenia was 10.3% (80/774), with rates of 6.7% (34/510) and 17.4% (46/264) in the primary and secondary prevention groups, respectively (P<0.001). The incidence of gradeⅣneutropenia was significantly lower in the second cy-cle of the treatment than in the first (cycle 1 vs. cycle 2: 17.1% vs. 5.3%, respectively, P=0.004, in the primary group; 46.5% vs. 11.3%, respectively, P<0.001, in the secondary group). The treatment-induced toxicity mainly involved bone pain, with 3.7% (8/217) and 1.8% (4/217) incidence rates for grade 1-2 and 3-4 bone pain, respectively. Conclusions: PEG-rhG-CSF administration can effectively reduce the incidence of FN (5.7%) when prophylactically applied to patients with non-myeloid malignant tumors. Primary prevention can sig- nificantly reduce the risk of grade IV neutropenia in all chemotherapy cycles relative to the secondary prevention.

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Research advances of tRNA-derived fragments in tumors

Yongqiang ZHOU ; Yongna WU ; Xun LI

Chinese Journal of Clinical Oncology.2019;46(14):745-749. doi:10.3969/j.issn.1000-8179.2019.14.005

The tRNA-derived fragments (tRF and tiRNA) are a newly discovered type of non-coding RNA (ncRNA) that has been found to be stably expressed in peripheral blood. Studies have shown that tRF and tiRNA play important roles in human tumors by regulating multiple processes, including gene expression and silencing, cell proliferation and apoptosis, and protein translation. The tissue-speci-ficity, high abundance, and stability of tRF and tiRNA, along with their broad-spectrum functional roles, confer them significant advan-tages for use in the field of oncology research. There is increasing evidence that aberrantly expressed tRF and tiRNA may be potential biomarkers or therapeutic targets for tumor diagnosis and prognosis. This paper summarizes the source, structure, biological charac-teristics, and functions of different tRF and tiRNA subtypes and explores their potential relationship with tumors and their underlying mechanisms in order to provide a novel idea for the early diagnosis and targeted therapy of tumors.

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Clinical management of common adverse effects of ibrutinib

Xi CHEN ; Haiyan YANG

Chinese Journal of Clinical Oncology.2019;46(14):750-754. doi:10.3969/j.issn.1000-8179.2019.14.951

As a first generation Bruton's tyrosine kinase inhibitor, ibrutinib is an oral small molecule targeted drug that has been prov-en to exhibit high efficacy and good safety in the treatment of B-cell lymphomas, including chronic lymphocytic leukemia or small lym-phocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL). Since ibrutinib first became available in China, increasing numbers of Chinese patients have benefited from it; however, with the increase in the number of patients, clinicians are faced with more adverse events, such as bleeding, atrial fibrillation, diarrhea, joint pain, among others, than traditional chemotherapeutic drugs. Because of the unique mechanism of action of ibrutinib, it is also necessary to pay attention to drug interactions when dealing with these adverse events. This review comprehensively summarizes the treatment strategies for ibrutinib adverse events in the literature and hopes to provide a reference for clinicians.

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Homing barriers and solutions for CAR-T cells in the treatment of solid tumors

Songlin YANG ; Lin LI ; Deren DUAN ; Zongliu HOU ; Jing TAN

Chinese Journal of Clinical Oncology.2019;46(14):755-759. doi:10.3969/j.issn.1000-8179.2019.14.892

Chimeric antigen receptor T (CAR-T) cell therapy is an emerging immunotherapy that has allowed for major breakthroughs in the treatment of hematological neoplasms. However, little progress has been made in the treatment of solid tumors, primarily due to the difficulty in homing to tumor tissues by CAR-T cells during treatment. The complex tumor microenvironment and the barrier function of tumor tissues prevent CAR-T cells from contacting tumor cells, thereby preventing them from exerting their antitumor ac-tivity. This review article summarizes not only the progress made in the study of homing disorders of CAR-T cells in the treatment of solid tumors but also the current methods to overcome these disorders.

Country

China

Publisher

中国抗癌协会

ElectronicLinks

http://www.cjco.cn

Editor-in-chief

E-mail

cjcotj@sina.com

Abbreviation

Chinese Journal of Clinical Oncology

Vernacular Journal Title

中国肿瘤临床

ISSN

1000-8179

EISSN

Year Approved

2010

Current Indexing Status

Currently Indexed

Start Year

1963

Description

1963-1983:天津医药·肿瘤学附刊(1966-1978.2:停刊); 1984-1985:肿瘤临床; 1986-:中国肿瘤临床

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