Journal of International Oncology

Paclitaxel liposome combined with cisplatin chemotherapy in nonsmall cell lung cancer with brain metastasis

LIU Na, CHENG Jun, MENG Ling-Zhan, LIU Yong

2015, 42 (5): 321-323. doi: 10.3760/cma.j.issn.1673422X.2015.05.001

Abstract ( 401 )

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ObjectiveTo evaluate the clinical efficacy and toxicity of paclitaxel liposome combined with cisplatin chemotherapy in NSCLC with brain metastasis. MethodsTwentyeight patients were newly diagnosed NSCLC with brain metastasis (confirmed by pathology or cytology). The patients were treated with paclitaxel liposome (135 mg/m2 ) on day 1 intravenous drip for 3 hours, cisplatin, 25 mg/m2 on day 13. The course of treatment was 21 days. The patients accepted the antiallergy treatment before chemotherapy. ResultsTwentyeight patients could be evaluated, and 101 treatment cycles were completed (3.6 cycles per patient). General lesion assessment presented that no patient got complete remission (CR), 13 patients (46.43%) got a partial response (PR), 11 (39.28%) had a stable disease(SD) and 4 (14.29％) had a progressive disease (PD). The objective response rate (RR) was 46.43％, and the disease control rate (DCR) was 85.71％. Local cerebral response assessment showed that no patient got CR, 6 patients (21.43%) got a PR, 15 (53.58%) had a SD and 4 (14.29％) had a PD. The RR was 21.43％, and the DCR was 85.71％. There was a significant difference in the RR (χ2=3.90, P=0.03) but not in the DCR (χ2=0.15, P=0.3) between the local cerebral disease and the general lesion. The median time to disease progression (TTP) for general lesion and local cerebral were 7.2 months and 6.2 months, respectively (χ2=6.43, P<0.05). The adverse reactions included bone marrow suppression, gastrointestinal reactions, elevated transaminases, alopecia, neurotoxicity, etc. All of these could be well controlled. ConclusionPaclitaxel liposome combined with cisplatin regimen demonstrates a higher efficacy and well tolerable against main metastasis of NSCLC, and the adverse effects are minor.

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Analysis of association of hepatitis B virus infection and family history of hepatocellular carcinoma with age at primary liver cancer

CHEN Tao-Yang, SUN Yan, WU Yan, WANG Jin-Bing, XUE Xue-Feng, YIN Yan-Ci

2015, 42 (5): 324-326. doi: 10.3760/cma.j.issn.1673422X.2015.05.002

Abstract ( 419 )

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ObjectiveTo explore the relationship of hepatitis B virus surface antigen (HBsAg) infection and family history of hepatocellular carcinoma (HCC) with age at primary liver cancer. MethodsTotally 1 359 cases of primary liver cancer were enrolled. Their data of sex, HBsAg status and family history informations of liver cancer were analyzed on the associations with diagnosis age. ResultsOf the 1 359 cases, 1 053 were males and 306 were females, their average age at diagnosis was (54.02±10.47) years (2084 years). For HBsAg positive cases, the average age at diagnosis was 51.99, significantly younger than that of HBsAg negative cases （61.23）, t=13.51, P=0.000. Cases with family history of HCC were diagnosed at a significantly earlier age than those without family history （52.53 vs 55.23, t=4.389, P=0.000）. In HBsAg positive cases, the average age at diagnosis showed a significant difference not only between males and females (51.18 vs 54.89, t=5.353, P=0.000), but also between cases with family history and cases without family history (51.33 vs 52.62, t=2.233, P=0.026). In HBsAg negative cases, the average age at diagnosis of males and females were 60.83 and 62.45 respectively (t=1.126, P=0.261). The average age at diagnosis of cases with family history and cases without family history were 59.58 and 61.92 respectively (t=1.728, P=0.085), both showed no significant difference. ConclusionCases of primary liver cancer with positiveHBsAg are diagnosed averagely 9.24 years younger than those with negativeHBsAg in Qidong. Sex and family history of HCC significantly advance hepatocarcinogenesis only in HBsAg positive individuals, not in HBsAg negative individuals.

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Expression and clinically pathological analysis of the protein CDC6 and HOXA5 in esophageal squamous cell carcinoma

FAN Li-Juan, ZHANG Jian, LIN Fan-Zhong, LI Hong-Yun

2015, 42 (5): 327-330. doi: 10.3760/cma.j.issn.1673422X.2015.05.003

Abstract ( 446 )

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ObjectiveTo investigate the expression and clinical significance of cell division cycle 6 (CDC6) and homeobox gene A5 (HOXA5) in esophageal squamous cell carcinoma. MethodsThe expression of CDC6 and HOXA5 in 51 specimens esophageal squamous cell carcinoma and 27 normal specimens esophageal tissues were evaluated by immunohistochemistry. Analyzed the relationship among the expression of CDC6 and HOXA5 protein and the clinicopathologic features of esophageal squamous cell carcinoma, along with the correlation between these two proteins. ResultsImmunohistochemical results showed that the positive expression rate of CDC6 and HOXA5 in esophageal squamous cell carcinoma tissue were 66.7%（34/51）and 60.8%(31/51), respectively, significantly higher than those in normal esophageal tissue18.5%(5/27),22.2%(6/27),（χ2=16.370，P=0.000；χ2=10.528，P=0.001）; There were significant positive correlation in the expression of CDC6 and HOXA5 and histological type（χ2=9.031，P=0.011；χ2=7.372，P=0.000）, TNM stage（χ2=10.474，P=0.015；χ2=11.667，P=0.009）, and there were no correlation in the expression of CDC6 and HOXA5 and age（χ2=0.000，P=1.000；χ2=0.001，P=0.972）, sex（χ2=0.049，P=0.824；χ2=0.107，P=0.743）, lymph node metastasis（χ2=3.186，P=0.074；χ2=2.212，P=0.137） in esophageal squamous cell carcinoma tissues. The expression of CDC6 and HOXA5 showed a positive correlation（r=0.454，P=0.001）. ConclusionThe positive expression rate of CDC6 and HOXA5 in esophageal squamous cell carcinoma tissue were significantly higher than in normal esophageal tissue and close correlation with TNM stage and differentiation. High expression of CDC6 and HOXA5 may play important roles in the occurrence, development and proliferation of esophageal squamous cell carcinoma．

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Correlation of YB1 upregulation and epithelialmesenchymal transition during tumorigenesis and progression of cervical carcinoma

LI Min, GUAN Hong, HU Xin-Rong, WANG Ying, WEI Qian, YANG Qing-Feng

2015, 42 (5): 331-335. doi: 10.3760/cma.j.issn.1673422X.2015.05.004

Abstract ( 376 )

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ObjectiveTo investigate the clinicopathologic significance of Ybox binding protein1 (YB1) expression in cervical cancer and its correlation with epithelialmesenchymal transition. MethodsA series of 202 samples, including 50 cases of normal cervical tissues, 100 cases of cervical intraepithelial neoplasia (CIN) and 52 cases of squamous cell carcinoma (SCC), were examined YB1 and Ecadherin by immunohistochemical staining. ResultsThe Ecadherin cell membrane immunoreactivity for normal/CINⅠ, CINⅡⅢ, and SCC tissues were 100%, 64% and 3.85%, respectively （χ2=40.909; χ2=119.088; χ2=25.274; P<0.05）. The negative and aberrant expression of Ecadherin was higher in metastatic SCC (100.0%, 20/20）than that in nonmetastatic SCC (68.75%, 22/32）(χ2=5.857, P=0.016). 94.23% （49/52） cases of SCC exhibited strong YB1 cytoplasmic immunoreactivity. The positive rates in normal/CINⅠand CINⅡⅢ were 0 (0/100）and 10.00% （5/50）（χ2=72.591； χ2=139.059； χ2=5.857; P<0.05）. The cytoplasmic expression of YB1 was higher in metastatic SCC (100.0%, 20/20）than that in nonmetastatic SCC (59.38%, 19/32）（χ2=10.833， P=0.001）. The rates were 60.71% （17/28） and 91.67% （22/24） in early stage SCC and late stage SCC （χ2=6.603, P=0.01）. ConclusionYB1 overexpression is associated with the malignant transformation of cervical epithelium, stage progression and metastasis of cervical cancer. The upregulation of YB1 is also associated with the downregulation of Ecadherin, and it may predict the malignant transformation of CIN and distal metastasis of cervical cancer.

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Efficacy and safety of recombinant human Adp53 injection combined with cisplatin in treating malignant pleural effusion: a Metaanalysis

ZHU Yan-Zhe, SUN Guo-Ping

2015, 42 (5): 336-341. doi: 10.3760/cma.j.issn.1673422X.2015.05.005

Abstract ( 513 )

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ObjectiveTo assess the efficacy and safety of recombinant human Adp53 (rAdp53) injection combined with cisplatin in treating malignant pleural effusion by conducting a Metaanalysis. MethodsA comprehensive collection of randomized controlled studies (RCTs) of rAdp53 combined with cisplatin versus single cisplatin in the treatment of malignant pleural effusion was retrieved form Cochrane Library, Pubmed, EMBase, CBM, CNKI, Wanfang and VIP databases. Metaanalysis was conducted by RevMan 5.2 software. ResultsTen RCTs involving 538 patients were identified in the study. The Metaanalysis results showed that rAdp53 combined with cisplatin group had a higher hydrothorax total remission rate than single cisplatin group (RR=1.67, 95%CI: 0.902.01; Z=5.51, P=0.000 01). The PS score in rAdp53 combined with cisplatin group was better than that in single cisplatin group (RR=1.76, 95%CI: 1.452.14; Z=5.69, P<0.000 01). The incidence rate of adverse reaction of heating in the former was higher than that in the latter (RR=3.10, 95%CI: 2.254.27; Z=6.94, P<0.000 01). There were no significant differences in adverse reactions of chest pain (RR=0.99, 95%CI: 0.501.96; Z=0.04, P=0.97), gastrointestinal reaction (RR=1.16, 95%CI: 0.901.50; Z=1.13, P=0.26) and marrow suppression (RR=1.09, 95%CI: 0.811.47; Z=0.59, P=0.55) between the two groups. ConclusionrAdp53 combined with cisplatin therapy for the treatment of malignant pleural effusion is superior to single cisplatin therapy. Mean while, fever is selflimited, and the safety is identified. It is worthy for promotion of rAdp53 injection combined with cisplatin in clinical treatment of advanced malignant pleural effusion.

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Association between polymorphism of interleukin28B rs12979860 T/C and susceptibility of hepatocellular carcinoma: a Metaanalysis

LIU Jia, ZHU Qin-Mei, HU Hong-Yi, WANG Su

2015, 42 (5): 342-346. doi: 10.3760/cma.j.issn.1673422X.2015.05.006

Abstract ( 318 )

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ObjectiveTo explore the correlation between polymorphism of interleukin28B (IL28B) rs12979860 T/C and susceptibility of hepatocellular carcinoma(HCC). MethodsAll eligible casecontrol studies published up to 20140930 were identified by searching PubMed, EMBase, CNKI, CBM, VIP and WanFang databases. Two reviews independently identified the literature according to inclusion and exclusion criteria. Metaanalysis was performed using Rev Man 5.2 and Stata 12.0 software. ResultsA total of 6 studies comprising 1 138 cases and 955 controls were finally included. Metaanalysis showed that IL28B rs12979860 T/C polymorphism was associated with the susceptibility of HCC. Compared with the genotype CC and CT+CC, genotype TT increased the risk of suffering from HCC(TT vs CC: OR=2.26, 95%CI: 1.403.64, Z=3.33, P= 0.000 9; TT vs CT+CC: OR=1.90, 95%CI: 1.232.93, Z=2.89, P= 0.004). In stratification analysis by ethnicity, we observed that the polymorphism of IL28B rs12979860 T/C was associated with the susceptibility of HCC among Caucasian populations (TT vs CC: OR=2.06, 95%CI: 1.223.47, Z=2.70, P=0.007; TT vs CT+CC: OR=1.71, 95%CI: 1.072.72, Z=2.23, P= 0.03). Conclusion The polymorphism of IL28B rs12979860 T/C is associated with the susceptibility of HCC, genotype TT may increase the susceptibility to HCC.

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Function and mechanism of PAR6 gene in the occurrence and development of tumor

HOU Xiu-Xiu, LING Zhi-Qiang, GE Ming-Hua

2015, 42 (5): 347-350. doi: 10.3760/cma.j.issn.1673422X.2015.05.007

Abstract ( 485 )

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Cell polarity is a common feature of many different types of cells, and it is essential to the normal differentiation and function of cells. Partitioning defective 6 (PAR6) gene encodes PAR6 protein, which is crucial to asymmetric cell division and polarized growth. PAR6 protein as a member of the PAR6 polarity complex, affects the synthetic of centrosome and protein recruitment to the centrosome. The abnormal number of centrosomal and the loss of cell polarity may eventually lead to the occurrence of tumor.

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Effects of IDH1 and IDH2 genes mutations on tumors

LIU Xiang, LING Zhi-Qiang

2015, 42 (5): 351-354. doi: 10.3760/cma.j.issn.1673422X.2015.05.008

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Isocitrate dehydrogenases (IDHs) are considered as key enzymes in the tricarboxylic acid cycle. Recurrent mutations in the IDH1 and IDH2 genes are recently found in several human cancers. Those point mutations specifically affect IDH1 and IDH2 active site arginine residues and confer a neomorphic enzyme function of directly catalyzing αketoglutarate (αKG) to R2hydroxyglutarate (R2HG). R2HG can competitively inhibits αKGdependent enzymes and may therefore contribute to the occurrence and development of tumor. In addition, Mutation status of IDH1 and IDH2 are closely relative to the progress and prognosis of certain tumor. Thus IDH1 and IDH2 are considered to be promising biomarkers for early diagnosis and prognosis and targeted therapy.

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Clinical relativity of PDCD5 with tumor

ZHOU Zhen, JIAN Jie-Kun, WANG Zhen-Bao, HU Jie, LIU Wei

2015, 42 (5): 355-357. doi: 10.3760/cma.j.issn.1673422X.2015.05.009

Abstract ( 353 )

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Programmed cell death 5 (PDCD5） is a new kind of programmed cell death regulation and control gene. PDCD5's expression is widespread, and evolution is conservative. PDCD5 has the effect of promoting a wide variety of tumor cells to apoptosis and inhibiting proliferation, such as lung cancer, liver cancer et al. Several laboratories' discoveries show that PDCD5's expression is significantly decreased when in some disease cases, especially in tumor cases. PDCD5, which is related to the clinical relevance of the tumor, has a great clinical value of discovering, diagnosis and treatment of the tumor.

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Research update on PD1 and its ligand PDL1 in malignant tumor

SHAO Jing-Yi, SUN Guo-Ping

2015, 42 (5): 358-360. doi: 10.3760/cma.j.issn.1673422X.2015.05.010

Abstract ( 397 )

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Programmed death1ligand(PDL1) is a new member of B7 family,whose receptor is programmed death1(PD1). The interaction between PDL1 and PD1 can downregulate the activation of immune response.There are some differences in the expression of PD1 and PDL1 in normal tissues and tumor tissues, which may provide a new way for the immunotherapy of carcinoma.

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Relation between alternatively spliced tissue factor and tumor

ZHAO Lin-Yan, JIANG Bo, ZHANG Ri

2015, 42 (5): 361-363. doi: 10.3760/cma.j.issn.1673422X.2015.05.011

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Serine/aginine rich (SR) protein, SR protein kinase and other enzymes participate in the composition of alternatively spliced tissue factor (asTF). Recently researchers have found that this protein takes a part in tumor angiogenesis, tumor progression, metastasis and so on, so the detection of its clinical content will be very significant.

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Recent advance in Pygopus

LI Ming-Cong, WANG Zhan-Xiang

2015, 42 (5): 364-366. doi: 10.3760/cma.j.issn.1673422X.2015.05.012

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Pygopus (Pygo) is a new discovered component of Wnt signaling, which is located in the downstream of its core protein βcatenin and can mediate βcatenin into nucleus and activate target gene transcription. Pygo plays an important role in mammalian embryonic development and tumor formation. Recent studies show that Pygo regulates stem cells, tumor cells and tumor stem cells by epigenetic mechanisms such as histone interpretations and modifications. Further insights into Pygo's functions and mechanisms will extend our knowledge of the Pygorelated tumors.

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Development of ABCC4 on various tumors and chemotherapy drugs

YAN Jin, ZHAO Xiao-Ting, JIANG Mei, YUE Wen-Tao

2015, 42 (5): 367-370. doi: 10.3760/cma.j.issn.1673422X.2015.05.013

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ATP binding cassette C4 (ABCC4, MRP4) plays an important role in transshipment physiologic, endogenous or exogenous substances. The over expression of ABCC4 gene has been found in many kinds of solid tumors and hematological malignancies. The target gene also influences metastasis and recurrence process. ABCC4 can reduce the intracellular concentration and the sensitivity of various chemotherapy drugs, which is bad for prognosis.

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Basic and clinical research progress of diffuse intrinsic pontine glioma

KONG Xiang-Yi, ZHOU Qiang-Yi, CHEN Ke-Yin, LIU Shuai, WANG Yu, MA Wen-Bin

2015, 42 (5): 371-373. doi: 10.3760/cma.j.issn.1673422X.2015.05.014

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Diffuse intrinsic pontine glioma (DIPG) is a highly invasive tumor located in the pons (middle) of the brain stem. They are usually diagnosed during childhood and account for 10%15% of primary brain tumors in children. DIPG has a very poor prognosis. Fewer than 10% of DIPG patients survive more than 2 years after diagnosis. The imaging manifestations of DIPG are typical, and biopsy is only performed in atypical cases. The tissue specimens of newly diagnosed DIPG are very few and limit its molecular biological research. Recent advances in surgical and molecularanalytic techniques have increased the safety of biopsy which has already been used in many clinical trials step by step. The research of DIPG's molecular pathogenesis and treatment is sure to achieve new breakthroughs.

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Surgical treatment of thyroid microcarcinoma

AN Cheng-Cheng, LI De-Qun

2015, 42 (5): 374-376. doi: 10.3760/cma.j.issn.1673422X.2015.05.015

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For thyroid microcarcinoma (TMC), the incidence is not obvious, the lesion is small, the symptoms are not distinctive and the progression is slow. Studies suggest that patients with the age over 45 years or below 15 years old, male, lesion over 5 mm and lymph node metastasis have poor prognosis and active operation treatment is needed. When in operation, the excision extension should take clinical data into consideration, and complete resection of the lesions and preservation of the normal tissue as much as possible should be done. For the patients with lymph node metastasis, lymph node dissection is feasible, and the central lymph node dissection is applicable for the negative lymph nodes. Reduce the risk of recurrence and metastasis, increase the survival rate of patients with tumor and improve the quality of life, become the prime target of the follow up, in which the standardized treatment of TMC plays a vital role.

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Progress of research on mTOR inhibitor in endocrine and HER2 targeted therapy resistance in breast cancer

DUAN Hai-Ming, ZHENG Yan-Ni, WANG Min-Quan

2015, 42 (5): 377-380. doi: 10.3760/cma.j.issn.1673422X.2015.05.016

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Mammalian target of rapamycin (mTOR) locates at the downstream of phosphatidylinositol 3 kinase (PI3K)protein kinase B (Akt) cell signal transduction pathway. Studies find that the abnormal activation of this pathway is correlated with the endocrine and drug resistance of anti human epidermal growth factor receptor2 (HER2) target therapy in breast cancer. The combination with mTOR inhibitors based on the past traditional drugs can block the pathway and reflect a favourable application prospect in preventing the development of resistance and restoring the initial sensitivity on tumor cells. mTOR inhibitors are expected to be the new hope for the treatment of breast cancer.

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Research progress of different chemotherapy regimens combined with radiotherapy for nonsmall cell lung cancer

SHI Sha-Peng, HAN Bo

2015, 42 (5): 381-384. doi: 10.3760/cma.j.issn.1673422X.2015.05.017

Abstract ( 409 )

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Advanced nonsmall cell lung cancer (NSCLC) accounts for all NSCLC 45%. In recent years, chemotherapy combined with radiotherapy has become a new standard for NSCLC. On NSCLC radiotherapy and chemotherapy (CRCT), radiation total dose, fractionation method, different chemotherapy combined with radiotherapy have many details in the efficiency and toxicity tolerance, which are still in the exploration.

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Second line treatment of nonsmall cell lung cancer

XU Qi-Ni, LI Xu-Yuan, WANG Hong-Biao

2015, 42 (5): 385-387. doi: 10.3760/cma.j.issn.1673422X.2015.05.018

Abstract ( 286 )

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The cytotoxic agents pemetrexed and docetaxel and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib are standard secondline therapies for nonsmall cell lung cancer. For patients without the EGFR mutation, more and more evidence has suggested the superiority of chemotherapy over targeted therapy. Adding targeted agents to standard secondline treatment is an trend of exploration, but without promising results nowadays. Crizotinib, targeting at anaplastic lymphoma kinase, has been shown excellent efficacy for secondline therapy in nonsmall cell lung cancer.

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Research progress of microRNAs in colorectal cancer therapy

LIN Xiao-Jing, XU Jing-Jing, CHEN Yan

2015, 42 (5): 388-391. doi: 10.3760/cma.j.issn.1673422X.2015.05.019

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he molecular targeted therapy method using microRNAs (miRNAs) is gradually stepping into people's vision. miRNAs affect colorectal cancer progress via abnormal expression in tumor cells or microenvironment. The high or low expressions of miRNAs in specific tissues probably have an impact on the expressions of oncogenes, tumor suppressor genes or other aspects including the surrounding environments, the metastases and the drug tolerance of tumors, thus contributing to curing the colorectal cancer. Nowadays, miRNA has entered the stage of animal experiments.

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The effect of p70S6K1 and 4EBP1 protein in colorectal cancer

ZHANG Shao-Hua, BI Jing-Wang

2015, 42 (5): 392-394. doi: 10.3760/cma.j.issn.1673422X.2015.05.020

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The phosphatidylinositide3kinase (PI3K)/ protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) pathway is recognized to have an important role in the development and progression of colorectal cancer (CRC). The most extensively characterized downstream targets of mTORC1 are ribosomal protein S6 kinase 1 (p70S6K1) and eukaryotic translation initiation factor (eIF) 4Ebinding protein 1 (4EBP1), both of which are crucial to the regulation of protein synthesis. The abnormal expression of p70S6K1 and 4EBP1 in CRC has become the focus of attention.

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